JP2020502541A - 全身型若年性特発性関節炎および川崎病を診断および識別するための組成物および方法 - Google Patents
全身型若年性特発性関節炎および川崎病を診断および識別するための組成物および方法 Download PDFInfo
- Publication number
- JP2020502541A JP2020502541A JP2019546767A JP2019546767A JP2020502541A JP 2020502541 A JP2020502541 A JP 2020502541A JP 2019546767 A JP2019546767 A JP 2019546767A JP 2019546767 A JP2019546767 A JP 2019546767A JP 2020502541 A JP2020502541 A JP 2020502541A
- Authority
- JP
- Japan
- Prior art keywords
- biomarkers
- sjia
- subject
- assays
- kit
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 93
- 208000011200 Kawasaki disease Diseases 0.000 title claims abstract description 69
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 title claims abstract description 69
- 208000003456 Juvenile Arthritis Diseases 0.000 title claims abstract description 21
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 title claims abstract description 21
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 title claims abstract description 21
- 230000009885 systemic effect Effects 0.000 title claims abstract description 19
- 239000000203 mixture Substances 0.000 title abstract description 13
- 239000000090 biomarker Substances 0.000 claims description 269
- 108010012820 Follistatin-Related Proteins Proteins 0.000 claims description 75
- 102000019203 Follistatin-Related Proteins Human genes 0.000 claims description 75
- 108010069316 Leukocyte L1 Antigen Complex Proteins 0.000 claims description 64
- 102000001109 Leukocyte L1 Antigen Complex Human genes 0.000 claims description 64
- 108010074051 C-Reactive Protein Proteins 0.000 claims description 62
- 102100032752 C-reactive protein Human genes 0.000 claims description 62
- 238000003556 assay Methods 0.000 claims description 33
- 238000003745 diagnosis Methods 0.000 claims description 33
- 239000012472 biological sample Substances 0.000 claims description 32
- 108700016890 S100A12 Proteins 0.000 claims description 29
- 101150097337 S100A12 gene Proteins 0.000 claims description 29
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 claims description 27
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 claims description 27
- 108700028909 Serum Amyloid A Proteins 0.000 claims description 27
- 102000054727 Serum Amyloid A Human genes 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 21
- 238000009739 binding Methods 0.000 claims description 20
- 230000027455 binding Effects 0.000 claims description 19
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims description 17
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims description 17
- 210000002966 serum Anatomy 0.000 claims description 17
- 208000015220 Febrile disease Diseases 0.000 claims description 14
- 239000011230 binding agent Substances 0.000 claims description 14
- 238000004949 mass spectrometry Methods 0.000 claims description 14
- 238000002965 ELISA Methods 0.000 claims description 12
- 239000012634 fragment Substances 0.000 claims description 12
- 238000003127 radioimmunoassay Methods 0.000 claims description 12
- 210000004369 blood Anatomy 0.000 claims description 11
- 239000008280 blood Substances 0.000 claims description 11
- 239000004005 microsphere Substances 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000000427 antigen Substances 0.000 claims description 8
- 108091007433 antigens Proteins 0.000 claims description 8
- 102000036639 antigens Human genes 0.000 claims description 8
- 238000012544 monitoring process Methods 0.000 claims description 8
- 238000004611 spectroscopical analysis Methods 0.000 claims description 7
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 6
- 238000001262 western blot Methods 0.000 claims description 6
- 108060003951 Immunoglobulin Proteins 0.000 claims description 5
- 238000000684 flow cytometry Methods 0.000 claims description 5
- 238000010166 immunofluorescence Methods 0.000 claims description 5
- 102000018358 immunoglobulin Human genes 0.000 claims description 5
- 238000004416 surface enhanced Raman spectroscopy Methods 0.000 claims description 5
- 239000003435 antirheumatic agent Substances 0.000 claims description 4
- 239000002988 disease modifying antirheumatic drug Substances 0.000 claims description 4
- 230000000284 resting effect Effects 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 150000003431 steroids Chemical class 0.000 claims description 2
- 102000058242 S100A12 Human genes 0.000 claims 6
- 238000010586 diagram Methods 0.000 abstract 1
- 239000000523 sample Substances 0.000 description 67
- 108090000623 proteins and genes Proteins 0.000 description 62
- 102000004169 proteins and genes Human genes 0.000 description 62
- 238000000540 analysis of variance Methods 0.000 description 26
- 102100029812 Protein S100-A12 Human genes 0.000 description 23
- 239000003153 chemical reaction reagent Substances 0.000 description 22
- 150000002500 ions Chemical class 0.000 description 20
- 238000001514 detection method Methods 0.000 description 19
- 239000012071 phase Substances 0.000 description 19
- 230000035945 sensitivity Effects 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 238000005516 engineering process Methods 0.000 description 16
- 230000014509 gene expression Effects 0.000 description 16
- 201000010099 disease Diseases 0.000 description 15
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- 206010003246 arthritis Diseases 0.000 description 9
- 238000003795 desorption Methods 0.000 description 9
- 238000001616 ion spectroscopy Methods 0.000 description 9
- 210000002381 plasma Anatomy 0.000 description 9
- 239000000463 material Substances 0.000 description 8
- 239000002594 sorbent Substances 0.000 description 8
- 238000000018 DNA microarray Methods 0.000 description 7
- -1 SAP (B) Proteins 0.000 description 7
- 239000003463 adsorbent Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 208000032672 Histiocytosis haematophagic Diseases 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 6
- 208000004987 Macrophage activation syndrome Diseases 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000011325 microbead Substances 0.000 description 6
- 239000002096 quantum dot Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 229920000669 heparin Polymers 0.000 description 5
- 229960002897 heparin Drugs 0.000 description 5
- 238000003018 immunoassay Methods 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 239000011859 microparticle Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 4
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 238000005571 anion exchange chromatography Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000002159 nanocrystal Substances 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000000672 surface-enhanced laser desorption--ionisation Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- 102100024321 Alkaline phosphatase, placental type Human genes 0.000 description 3
- 208000006820 Arthralgia Diseases 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 3
- 108090001090 Lectins Proteins 0.000 description 3
- 102000004856 Lectins Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 208000035977 Rare disease Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 108091005608 glycosylated proteins Proteins 0.000 description 3
- 102000035122 glycosylated proteins Human genes 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000002523 lectin Substances 0.000 description 3
- 238000007477 logistic regression Methods 0.000 description 3
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000007837 multiplex assay Methods 0.000 description 3
- 108010031345 placental alkaline phosphatase Proteins 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
- 102100036664 Adenosine deaminase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 2
- 101001091269 Escherichia coli Hygromycin-B 4-O-kinase Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 101001091268 Streptomyces hygroscopicus Hygromycin-B 7''-O-kinase Proteins 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 238000003748 differential diagnosis Methods 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000002082 metal nanoparticle Substances 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 239000012465 retentate Substances 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 1
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
- KEJYUAMBFQZVEH-UHFFFAOYSA-N 3-cyano-2-hydroxy-3-phenylprop-2-enoic acid Chemical compound OC(=O)C(O)=C(C#N)C1=CC=CC=C1 KEJYUAMBFQZVEH-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 108090000363 Bacterial Luciferases Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101000800130 Bos taurus Thyroglobulin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BQENDLAVTKRQMS-SBBGFIFASA-L Carbenoxolone sodium Chemical compound [Na+].[Na+].C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C([O-])=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](OC(=O)CCC([O-])=O)C1(C)C BQENDLAVTKRQMS-SBBGFIFASA-L 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000178548 Cerianthus Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108050000784 Ferritin Proteins 0.000 description 1
- 102000008857 Ferritin Human genes 0.000 description 1
- 238000008416 Ferritin Methods 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 206010023203 Joint destruction Diseases 0.000 description 1
- 108010025815 Kanamycin Kinase Proteins 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000574441 Mus musculus Alkaline phosphatase, germ cell type Proteins 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 241001495084 Phylo Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010058556 Serositis Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 101710146079 Xanthine-guanine phosphoribosyltransferase Proteins 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 108010004469 allophycocyanin Proteins 0.000 description 1
- 102000005840 alpha-Galactosidase Human genes 0.000 description 1
- 108010030291 alpha-Galactosidase Proteins 0.000 description 1
- AFVLVVWMAFSXCK-VMPITWQZSA-N alpha-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(\C#N)=C\C1=CC=C(O)C=C1 AFVLVVWMAFSXCK-VMPITWQZSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 102000006646 aminoglycoside phosphotransferase Human genes 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 238000004630 atomic force microscopy Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 108091005948 blue fluorescent proteins Proteins 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000009193 crawling Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 230000005059 dormancy Effects 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000000572 ellipsometry Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 108010021843 fluorescent protein 583 Proteins 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 206010019847 hepatosplenomegaly Diseases 0.000 description 1
- 239000012145 high-salt buffer Substances 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 238000004989 laser desorption mass spectroscopy Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 208000018555 lymphatic system disease Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000003498 protein array Methods 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 108010054624 red fluorescent protein Proteins 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- PCMORTLOPMLEFB-ONEGZZNKSA-N sinapic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-ONEGZZNKSA-N 0.000 description 1
- PCMORTLOPMLEFB-UHFFFAOYSA-N sinapinic acid Natural products COC1=CC(C=CC(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-UHFFFAOYSA-N 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001920 surface-enhanced laser desorption--ionisation mass spectrometry Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/65—Raman scattering
- G01N21/658—Raman scattering enhancement Raman, e.g. surface plasmons
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4737—C-reactive protein
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
- G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Rehabilitation Therapy (AREA)
- Rheumatology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Biophysics (AREA)
Abstract
Description
本出願は、35U.S.C.第119条(e)の下で、2016年11月11日に出願された米国特許出願第62/420,991号(参照によりその全体が本明細書に組み込まれる)に対しての優先権を主張するものである。
本明細書中にさらに記載するように、本開示は、sJIAを有する患者を診断し、sJIAとKDおよび他の熱性疾患を有する患者と識別するための方法、組成物、キットなどを提供することにより、まだ満たされていない必要性を満たすものである。したがって、本明細書に記載された実施形態は、有利なことに、診断時間および診断費用を実質的に減少し、これにより、患者の痛みを軽減させ、これらの状態に罹患した患者に対する適切な治療の享受および該治療への迅速なアクセスを提供する。
本開示は、sJIA、KD、および/またはFIの診断および識別において有利に使用することができる特定のバイオマーカーおよびバイオマーカーの組み合わせの発見に基づく。一般的に言えば、本開示のバイオマーカーは、SJIA、KD、およびFIを有する患者から得られた試料中で示差的に発現される生体化合物、特にタンパク質を含む。より特定的には、本開示のバイオマーカーは、典型的には、健常な対照と比較したときのおよび/または互いに比較したとき(例えばsJIA対KD対FI)の、SJIA、KD、およびFIを有する対象から得られた試料中の量および/または頻度の差を示す。
さらに別の態様において、本開示は、sJIA、KDおよび/またはFIを診断または識別するためのキットおよび装置であって、対象から得られた生体試料中の本明細書に記載されるバイオマーカーのレベルを検出および決定するために必要なまたは所望される作用物質を含有する、キットを提供する。
SJIAおよびKDの識別に有効なバイオマーカーの同定
合計39人の健常な対照対象、42人のKD対象、42人のFI対象、42人のsJIAフレア対象、および42人のsJIA休止対象由来の血漿試料を、5点希釈系列を使用して、タンパク質マイクロアレイにより検査した。アレイの設計は、各バイオマーカーに対する捕捉抗体の3つのスポットを含み、各試料について3つ組でのデータ収集が可能となるようにした。各アレイはまた、陽性対照およびブランク対照を含んだ。データをGraphPad Prismバージョン11を用いて処理し、統計的分析をSAS Institute Inc.のJMPproバージョン12で行った。
患者のモニタリングおよびフレア発生の予測
この例では、sJIAの活性(フレア)および不活性(休止)段階中の患者でバイオマーカーを評価した。分析する血漿試料は、フレアおよび休止の明確なサイクルを経た同じ対象から収集した。この手法を使用して、3つの特定のバイオマーカー、CRP、カルプロテクチン、およびS100A12が、疾患状態の変化に関連する明確な発現パターン、すなわち、フレアが増加し、休止が減少することを示すことが見出された(図4)。したがって、これらのようなバイオマーカーは、例えば、sJIAを有する対象をモニタリングするための方法および/または活性フレアの開始を予測するための方法で使用し得る。
1.Srivastava,Shivani et.al(2010)Monocytes are Resistant to Apoptosis in Systemic Juvenile Idiopathic Arthritis.Clinical Immunology136,257−268.
2.Woo,P.(2006)Systemic Juvenile Idiopathic Arthritis:Diagnosis,Management,and Outcome.Nature Clinical Practice Rheumatology2.
3.Huang,Jing−Long.(2012)New Advances in Juvenile Idiopathic Arthritis,Chang Gung MedJ35.
4.Pascual,V.(2005)Role of Interleukin−1(IL−1)in the Pathogenesis of Systemic Onset Juvenile Idiopathic Arthritis and Clinical Response to IL−1 Blockade.Journal of Experimental Medicine201,1479−1486.
5.Aronson,J.K.(2006)Editors’View Rare Diseases and Orphan Drugs,British Journal of Clinical Pharmacology61,243−245.
6.Reiff,A.(2012)Treatment of Systemic Juevnile Idiopathic Arthritis with Tocilizulmab−the Role of Anti−Interleukin−6 Therapy after a Decade of Treatment Biologics in Therapy,Cancer Biology and Therapy2,1−12.
7.Ling,X.B.;Park,J.L.;Carroll,T.;Nguyen,K.D.;Lau,K.;Macaubas,C.;Chen,E.;Lee,T.;Sandborg,C.;Milojevic,D.;Kanegaye,J.T.;Gao,S.;Burns,J.;Schilling,J.;Mellins,E.D.(2010)Plasma Profiles in Active Systemic Juvenile Idiopathic Arthitis:Biomarkers and Biological Implications,PROTEOMICS10,4415−4430.
8.Gorelik,Mark et.al(2013)Follistatin−like Protein 1 and Ferritin/Erythrocyte Sedimentation Rate Ratio are Potential Biomarkers for Dysregulated Gene Expression and Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis.The Journal of Rheumatology40,1191−1199.
9.Ravelli,Angelo;Martini,Alberto.(2007)Juvenile Idiopathic Arthritis.The Lancet36.767−778.
10.Vastert,S.J.;Kuis,W.;Grom,A.A.(2009)Systemic JIA:New Developments in the Understanding of the Pathophysiology and Therapy.Best Pract Clin Rhuematol 23,655−664.11.Mottonen,T.;Hannonen,P.;Leirisalo−Repo,M.;Nissila,M.;Kautiainen,H.;Korpela,M.;Laasonen,L.;Julkunen,H.;Luukkainen,R.;Vuori,K.;Paimela,L.;Blafield,H.;Hakala,M.;Ilva,K.;Yli−Kerttula,U.;Puolakka,K.;Jarvinen,P.;Hakola,M.;Piirainen,H.;Ahonen,J.;Palvimaki,I.;Forsberg,S.;Koota,K.;Friman,C.(1999)Comparison of Combination Therapy with Single−Drug Therapy in Early Rheumatoid Arthritis:a Randomized Trial.The Lancet 353,1568−1573.
12.Childhood Arthritis and Rheumatology Alliance(CARRA):Unpublished Data,2013.
13.Pascual,Virginia;Allantaz,Florence;Patel,Pinakeen;Palucka,Karolina,A;Chaussabel,Damien;Banchereau,Jacques(2008)How the Study of Children With Rheumatic Diseases Identified Interferon−α and Interleukin−1as Novel Therapeutic Targets.Immunological Reviews223,39−59.
14.Angeloni,Stephen et.al(2013)A Collection of Methods and Protocols for Developing multiplex assays with xMap Technology,Luminex xMap Cookbook.1st edition,1−116.
15.Microbead Trappind Device(2012).
16.DeJager,W.;Velthuis,H.T.;Prakken,B.J.;Kuis,W.;Rijkers,G.T.(2003)Simulataneous Detection of 15 Human Cytokines in a Single Sample of Stimulated Peripheral Blood Mononuclear Cells.Clinical and Vaccine Immunology10,133−139.
17.Lawson,S.;Lunney,J.;Zuckermann,F.;Fern;Osorio,O.;Nelson,E.;Welbon,C.;Clement,T.;Fang,Y.;Wong,S.;Kulas,K.;Christopher−Hennings,J.;Osorio,F.(2010)Development of an 8−plex Luminex assay to Detect Swine Cytokines for Vaccine Development:Assessment of Immunity after Porcine Reproductive and Respiratory Syndrome Virus(PRRSV)Vaccination.Vaccine28,5356−5364.
18.Bjerre,M.;Hansen,T.K.;Flyvbjerg,A.;Tonnesen,E.(2009)Simultaneous Detection of Porcine Cytokines by Multiplex Analysis:Development of Magnetic Bioplex Assay.Veterinary Immunology and Immunopathology 130,53−58.
19.Funding,M.;Hansen,T.K.;Gjedsted,J.;Ehlers,N.(2006)Simultaneous Quantification of 17 Immune Mediators in Aqueous Humour from Patients with Corneal Rejection.Acta Ophthalmologica Scandinavica 84,759−765.
Claims (39)
- 対象における全身型若年性特発性関節炎(sJIA)を診断する方法であって、(i)前記対象から得られた生体試料中の複数のバイオマーカーの各々のレベルを決定する工程であって、前記複数のバイオマーカーがカルプロテクチンおよびフォリスタチン関連タンパク質1(FSTL−1)を含む、工程と、(ii)前記複数のバイオマーカーの各々のレベルを対応する所定の診断閾値と比較し、それによって前記対象におけるsJIAの診断を提供する工程と、を含む、方法。
- 前記複数のバイオマーカーが、C反応性タンパク質(CRP)、血清アミロイドP(SAP)、およびS100A12のうちの少なくとも1つをさらに含む、請求項1に記載の方法。
- 前記複数のバイオマーカーが、アルファ−2マクログロブリン(A2M)、血清アミロイドA(SAA)、およびアポリポタンパク質A1のうちの少なくとも1つをさらに含む、請求項1または2に記載の方法。
- 前記複数のバイオマーカーが3つ以下のバイオマーカーを含む、請求項1〜3のいずれか一項に記載の方法。
- 前記複数のバイオマーカーが4つ以下のバイオマーカーを含む、請求項1〜3のいずれか一項に記載の方法。
- 前記対象においてsJIAの診断と川崎病(KD)の診断とを識別することをさらに含む、請求項1〜5のいずれか一項に記載の方法。
- 前記対象においてsJIAの診断と熱性疾患(FI)の診断とを識別することをさらに含む、請求項1〜6のいずれか一項に記載の方法。
- 前記生体試料が血液または血漿である、請求項1〜7のいずれか一項に記載の方法。
- 各バイオマーカーのレベルを決定する前記工程が、酵素結合免疫吸着アッセイ(ELISA)、ラジオイムノアッセイ(RIA)、免疫蛍光アッセイ(IFA)、サンドイッチアッセイ、磁気捕捉アッセイ、微小球捕捉アッセイ、ウェスタンブロットアッセイ、表面増強ラマン分光法(SERS)、フローサイトメトリー、および質量分析からなる群から選択されるアッセイを行うことを含む、請求項1〜8のいずれか一項に記載の方法。
- 対象における全身型若年性特発性関節炎(sJIA)、川崎病(KD)、および熱性疾患(FI)の診断を識別する方法であって、(i)前記対象から得られた生体試料中の複数のバイオマーカーの各々のレベルを決定する工程であって、前記複数のバイオマーカーがカルプロテクチンおよびフォリスタチン関連タンパク質1(FSTL−1)を含む、工程と、(ii)前記複数のバイオマーカーの各々のレベルを対応する所定の診断閾値と比較し、それによって前記対象におけるSJIA、KD、またはFIの診断を提供する工程と、を含む、方法。
- 前記複数のバイオマーカーが、C反応性タンパク質(CRP)、血清アミロイドP(SAP)、およびS100A12のうちの少なくとも1つをさらに含む、請求項10に記載の方法。
- 前記複数のバイオマーカーが、アルファ−2マクログロブリン(A2M)、血清アミロイドA(SAA)、およびアポリポタンパク質A1のうちの少なくとも1つをさらに含む、請求項10または11記載の方法。
- 前記複数のバイオマーカーが3つ以下のバイオマーカーを含む、請求項10〜12のいずれか一項に記載の方法。
- 前記複数のバイオマーカーが4つ以下のバイオマーカーを含む、請求項10〜12のいずれか一項に記載の方法。
- 前記生体試料が血液または血漿である、請求項10〜14のいずれか一項に記載の方法。
- 各バイオマーカーのレベルを決定する前記工程が、酵素結合免疫吸着アッセイ(ELISA)、ラジオイムノアッセイ(RIA)、免疫蛍光アッセイ(IFA)、サンドイッチアッセイ、磁気捕捉アッセイ、微小球捕捉アッセイ、ウェスタンブロットアッセイ、表面増強ラマン分光法(SERS)、フローサイトメトリー、および質量分析からなる群から選択されるアッセイを行うことを含む、請求項10〜15のいずれか一項に記載の方法。
- SJIA、KD、またはFIの診断を有することが疑われる対象における治療の必要性についての医師による決定を容易にする方法であって、(i)前記対象から得られた生体試料中の複数のバイオマーカーの各々のレベルを決定する工程であって、前記複数のバイオマーカーがカルプロテクチンおよびフォリスタチン関連タンパク質1(FSTL−1)を含む、工程と、(ii)前記対象におけるSJIA、KD、およびFIの診断を識別するために、前記複数のバイオマーカーの各々のレベルを対応する所定の診断閾値と比較し、それによってSJIA、KD、またはFIの治療を前記対象に行う必要性についての医師による決定を容易にする工程と、を含む、方法。
- 前記複数のバイオマーカーが、C反応性タンパク質(CRP)、血清アミロイドP(SAP)、およびS100A12のうちの少なくとも1つをさらに含む、請求項17に記載の方法。
- 前記複数のバイオマーカーが、アルファ−2マクログロブリン(A2M)、血清アミロイドA(SAA)、およびアポリポタンパク質A1のうちの少なくとも1つをさらに含む、請求項17または18記載の方法。
- 前記複数のバイオマーカーが3つ以下のバイオマーカーを含む、請求項17〜19のいずれか一項に記載の方法。
- 前記複数のバイオマーカーが4つ以下のバイオマーカーを含む、請求項17〜19のいずれか一項に記載の方法。
- 前記生体試料が血液または血漿である、請求項17〜21のいずれか一項に記載の方法。
- 各バイオマーカーのレベルを決定する前記工程が、酵素結合免疫吸着アッセイ(ELISA)、ラジオイムノアッセイ(RIA)、免疫蛍光アッセイ(IFA)、サンドイッチアッセイ、磁気捕捉アッセイ、微小球捕捉アッセイ、ウェスタンブロットアッセイ、表面増強ラマン分光法(SERS)、フローサイトメトリー、および質量分析からなる群から選択されるアッセイを行うことを含む、請求項17〜22のいずれか一項に記載の方法。
- 前記SJIAの治療が、非ステロイド系抗炎症薬(NSAID)、疾患修飾性抗リウマチ薬(DMARD)、生物学的薬剤、ならびに関節内および経口ステロイドからなる群から選択される1つ以上の薬剤を含む、請求項17〜23のいずれか一項に記載の方法。
- 前記KDの治療が免疫グロブリン静注(IVIG)を含む、請求項17〜24のいずれか一項に記載の方法。
- 対象におけるsJIAを診断するためのキットであって、前記キットは、対象から得られた生体試料中の複数のバイオマーカーのレベルを決定するのに有効な結合作用物質を含み、前記複数のバイオマーカーがカルプロテクチンおよびフォリスタチン関連タンパク質1(FSTL−1)を含む、キット。
- 前記複数のバイオマーカーが、C反応性タンパク質(CRP)、血清アミロイドP(SAP)、およびS100A12のうちの少なくとも1つをさらに含む、請求項26に記載のキット。
- 前記複数のバイオマーカーが、アルファ−2マクログロブリン(A2M)、血清アミロイドA(SAA)、およびアポリポタンパク質A1のうちの少なくとも1つをさらに含む、請求項26または27に記載のキット。
- 前記複数のバイオマーカーが3つ以下のバイオマーカーを含む、請求項26〜28のいずれか一項に記載のキット。
- 前記複数のバイオマーカーが4つ以下のバイオマーカーを含む、請求項26〜29のいずれか一項に記載のキット。
- 前記結合作用物質が抗体またはその結合断片である、請求項26〜30のいずれか一項に記載のキット。
- 前記キットが、前記対象においてsJIAの診断と川崎病(KD)の診断とを識別するのに有効である、請求項26〜31のいずれか一項に記載のキット。
- 前記キットが、前記対象においてsJIAの診断と熱性疾患(FI)の診断とを識別するのに有効である、請求項26〜32のいずれか一項に記載のキット。
- 前記キットがラテラルフロー装置を含む、請求項26〜33のいずれか一項に記載のキット。
- 前記キットが、複数のバイオマーカーに特異的な抗体またはその抗原結合断片を含むラテラルフロー装置を含む、請求項26〜34のいずれか一項に記載のキット。
- 治療の必要性についての医師による決定を容易にするために、対象におけるSJIAの進行をモニタリングする方法であって、(i)前記対象から生体試料を得る工程と、(ii)前記生体試料において、複数のバイオマーカーの各々のレベルを決定する工程であって、前記複数のバイオマーカーが少なくともS100A12、CRP、およびカルプロテクチンを含む、工程と、(iii)前記複数のバイオマーカーの各々のレベルを対応する所定の診断閾値と比較し、それによって前記対象におけるSJIAをモニタリングする工程と、を含む、方法。
- 前記対象におけるS100A12、CRP、およびカルプロテクチンのレベルの、それらの所定の診断閾値に対する上昇が、休止SJIA段階から活性SJIAフレア段階への進行を予測する、請求項36に記載の方法。
- 前記生体試料が血液または血漿である、請求項36または37に記載の方法。
- 各バイオマーカーのレベルを決定する前記工程が、酵素結合免疫吸着アッセイ(ELISA)、ラジオイムノアッセイ(RIA)、免疫蛍光アッセイ(IFA)、サンドイッチアッセイ、磁気捕捉アッセイ、微小球捕捉アッセイ、ウェスタンブロットアッセイ、表面増強ラマン分光法(SERS)、フローサイトメトリー、および質量分析からなる群から選択されるアッセイを行うことを含む、請求項36〜38のいずれか一項に記載の方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022084414A JP2022110148A (ja) | 2016-11-11 | 2022-05-24 | 全身型若年性特発性関節炎および川崎病を診断および識別するための組成物および方法 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662420991P | 2016-11-11 | 2016-11-11 | |
US62/420,991 | 2016-11-11 | ||
PCT/US2017/061057 WO2018089764A1 (en) | 2016-11-11 | 2017-11-10 | Compositions and methods for diagnosing and differentiating systemic juvenile idiopathic arthritis and kawasaki disease |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022084414A Division JP2022110148A (ja) | 2016-11-11 | 2022-05-24 | 全身型若年性特発性関節炎および川崎病を診断および識別するための組成物および方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2020502541A true JP2020502541A (ja) | 2020-01-23 |
JP2020502541A5 JP2020502541A5 (ja) | 2020-10-22 |
JP7132233B2 JP7132233B2 (ja) | 2022-09-06 |
Family
ID=62110362
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019546767A Active JP7132233B2 (ja) | 2016-11-11 | 2017-11-10 | 全身型若年性特発性関節炎および川崎病を診断および識別するための組成物および方法 |
JP2022084414A Pending JP2022110148A (ja) | 2016-11-11 | 2022-05-24 | 全身型若年性特発性関節炎および川崎病を診断および識別するための組成物および方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022084414A Pending JP2022110148A (ja) | 2016-11-11 | 2022-05-24 | 全身型若年性特発性関節炎および川崎病を診断および識別するための組成物および方法 |
Country Status (4)
Country | Link |
---|---|
US (1) | US11448648B2 (ja) |
EP (1) | EP3529596A4 (ja) |
JP (2) | JP7132233B2 (ja) |
WO (1) | WO2018089764A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113252806B (zh) * | 2021-03-25 | 2023-08-29 | 嘉兴学院 | S-腺苷同型半胱氨酸在制备用于诊断或治疗川崎病的产品中的用途 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110045507A1 (en) * | 2008-01-29 | 2011-02-24 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Fstl-1 as a biomaker of inflammation |
WO2012019099A2 (en) * | 2010-08-05 | 2012-02-09 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Follistatin-like-protein-1 as a biomarker for inflammatory disorders |
US20130052665A1 (en) * | 2011-08-25 | 2013-02-28 | Bruce Xuefeng Ling | Methods for diagnosis of systemic juvenile idiopathic arthritis |
JP2015505245A (ja) * | 2011-12-29 | 2015-02-19 | ベイラー リサーチ インスティテュートBaylor Research Institute | 川崎病のためのバイオマーカー |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2236186B (en) | 1989-08-22 | 1994-01-05 | Finnigan Mat Gmbh | Process and device for laser desorption of analyte molecular ions, especially of biomolecules |
US5045694A (en) | 1989-09-27 | 1991-09-03 | The Rockefeller University | Instrument and method for the laser desorption of ions in mass spectrometry |
EP0597960B1 (en) | 1991-08-10 | 1999-01-20 | Medical Research Council | Treatment of cell populations |
ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
JP3720353B2 (ja) | 1992-12-04 | 2005-11-24 | メディカル リサーチ カウンシル | 多価および多重特異性の結合タンパク質、それらの製造および使用 |
PT700521E (pt) | 1993-05-28 | 2003-10-31 | Baylor College Medicine | Metodo e espectrometro de massa para dessorcao e ionizacao de analitos |
US5981180A (en) | 1995-10-11 | 1999-11-09 | Luminex Corporation | Multiplexed analysis of clinical specimens apparatus and methods |
DE69638321D1 (de) | 1995-10-11 | 2011-03-03 | Luminex Corp | Gleichzeitige mehrfachanalyse klinischer proben |
NZ516848A (en) | 1997-06-20 | 2004-03-26 | Ciphergen Biosystems Inc | Retentate chromatography apparatus with applications in biology and medicine |
EP1023464B1 (en) | 1997-10-14 | 2017-07-26 | Luminex Corporation | Precision fluorescently dyed particles and methods of making and using same |
US6537749B2 (en) | 1998-04-03 | 2003-03-25 | Phylos, Inc. | Addressable protein arrays |
US6406921B1 (en) | 1998-07-14 | 2002-06-18 | Zyomyx, Incorporated | Protein arrays for high-throughput screening |
WO2000056934A1 (en) | 1999-03-24 | 2000-09-28 | Packard Bioscience Company | Continuous porous matrix arrays |
WO2013167727A2 (en) * | 2012-05-11 | 2013-11-14 | Westfaelische Wilhelms-Universitaet Muenster | Method for determining arthritis relapse risk |
-
2017
- 2017-11-10 US US16/349,233 patent/US11448648B2/en active Active
- 2017-11-10 JP JP2019546767A patent/JP7132233B2/ja active Active
- 2017-11-10 WO PCT/US2017/061057 patent/WO2018089764A1/en unknown
- 2017-11-10 EP EP17870447.4A patent/EP3529596A4/en active Pending
-
2022
- 2022-05-24 JP JP2022084414A patent/JP2022110148A/ja active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110045507A1 (en) * | 2008-01-29 | 2011-02-24 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Fstl-1 as a biomaker of inflammation |
WO2012019099A2 (en) * | 2010-08-05 | 2012-02-09 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Follistatin-like-protein-1 as a biomarker for inflammatory disorders |
US20130052665A1 (en) * | 2011-08-25 | 2013-02-28 | Bruce Xuefeng Ling | Methods for diagnosis of systemic juvenile idiopathic arthritis |
JP2015505245A (ja) * | 2011-12-29 | 2015-02-19 | ベイラー リサーチ インスティテュートBaylor Research Institute | 川崎病のためのバイオマーカー |
Non-Patent Citations (6)
Title |
---|
DAVID C WILSON: "Follistatin-like protein 1 is a mesenchyme-derived inflammatory protein and may represent a biomarke", ARTHRITIS RHEUM, vol. 62, no. 8, JPN6021033415, August 2010 (2010-08-01), pages 2510 - 2516, ISSN: 0004723974 * |
FROSCH M: "The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleuk", ARTHRITIS RHEUM, vol. 60, no. 3, JPN6021033414, March 2009 (2009-03-01), pages 883 - 891, ISSN: 0004723975 * |
GORELIK M: "Follistatin-like protein 1 and the ferritin/erythrocyte sedimentation rate ratio are potential bioma", J RHEUMATOL, vol. 40, no. 7, JPN6021033413, 15 May 2013 (2013-05-15), pages 1191 - 1199, ISSN: 0004723976 * |
GUO Q: "Serum calprotectin-a promising diagnostic marker for adult-onset Still's disease", CLIN RHEUMATOL, vol. 35, no. 1, JPN6021033412, 7 November 2015 (2015-11-07), pages 73 - 79, XP035892404, ISSN: 0004837828, DOI: 10.1007/s10067-015-3108-6 * |
SUSAN SHENOI: "Comparison of biomarkers for systemic juvenile idiopathic arthritis", PEDIATR RES, vol. 78, no. 5, JPN6021033417, 12 August 2015 (2015-08-12), pages 554 - 559, XP055682837, ISSN: 0004723973, DOI: 10.1038/pr.2015.144 * |
XUEFENG B. LING: "Plasma profiles in active systemic juvenile idiopathic arthritis: biomarkers and biological implicat", PROTEOMICS, vol. 10, no. 24, JPN6021033418, December 2010 (2010-12-01), pages 4415 - 4430, XP055407553, ISSN: 0004579193, DOI: 10.1002/pmic.201000298 * |
Also Published As
Publication number | Publication date |
---|---|
WO2018089764A1 (en) | 2018-05-17 |
JP2022110148A (ja) | 2022-07-28 |
US20190293644A1 (en) | 2019-09-26 |
US11448648B2 (en) | 2022-09-20 |
EP3529596A1 (en) | 2019-08-28 |
EP3529596A4 (en) | 2020-05-13 |
JP7132233B2 (ja) | 2022-09-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11619637B2 (en) | Biomarkers and diagnostic methods for Alzheimer's disease and other neurodegenerative disorders | |
US9651563B2 (en) | Biomarkers for liver fibrosis | |
CN107110867B (zh) | 用于肝癌诊断的生物标记物及其用途 | |
CN109564225B (zh) | 作为指示不良事件的标志物的组蛋白和/或proADM | |
US20130052665A1 (en) | Methods for diagnosis of systemic juvenile idiopathic arthritis | |
EP2796878A1 (en) | New biomarkers for diagnosis, prediction and/or prognosis of sepsis and uses thereof | |
JP2021036233A (ja) | バイオマーカーとしての遊離ヒストンタンパク質 | |
WO2007082586A1 (en) | Method and markers for the diagnosis of renal diseases | |
WO2010141469A2 (en) | Protein biomarkers and therapeutic targets for autoimmune and alloimmune diseases | |
JP7194673B2 (ja) | 臓器障害を示すマーカーとしてのヒストンおよび/またはproADM | |
US20150377905A1 (en) | Methods for diagnosis of kawasaki disease | |
US20210116462A1 (en) | Methods and Compositions for the Diagnosis and Treatment of Kawasaki Disease | |
US20060286602A1 (en) | Method and markers for the diagnosis of renal diseases | |
JP2021503610A (ja) | 神経損傷および/または疾患のタンパク質バイオマーカー指標及びその使用の方法 | |
US20140236166A1 (en) | Biomarkers for distinguishing benign, pre-malignant, and malignant pancreatic cysts | |
KR101390590B1 (ko) | 췌장암 재발 예후 예측용 마커 및 이의 용도 | |
JP2022110148A (ja) | 全身型若年性特発性関節炎および川崎病を診断および識別するための組成物および方法 | |
KR101390543B1 (ko) | 췌장암 진단용 마커 및 이의 용도 | |
KR102131860B1 (ko) | 아르기닌이 메틸화된 ggt1에 특이적으로 결합하는 대장암 진단용 바이오마커 조성물 | |
US20210063394A1 (en) | Methods and compositions for diagnosis of rickettsia infection | |
KR101859812B1 (ko) | 간암 화학 색전술 치료 예후 예측을 위한 바이오마커 및 그 용도 | |
Sato et al. | Identification of Differentially Expressed Proteins in the Serum for Systemic Juvenile Idiopathic Arthritis Using Next-generation Proteomics | |
US20110236912A1 (en) | Systems and methods for characterizing lupus erythematosus | |
JP2012103238A (ja) | 免疫複合体の網羅的解析方法および新規関節リウマチバイオマーカー |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200910 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200910 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20210817 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210826 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211105 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220218 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220309 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220524 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220729 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220825 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7132233 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |