CN101687908B - 类风湿性关节炎特异性自身抗体的抗原决定簇及其用途 - Google Patents
类风湿性关节炎特异性自身抗体的抗原决定簇及其用途 Download PDFInfo
- Publication number
- CN101687908B CN101687908B CN2008800215523A CN200880021552A CN101687908B CN 101687908 B CN101687908 B CN 101687908B CN 2008800215523 A CN2008800215523 A CN 2008800215523A CN 200880021552 A CN200880021552 A CN 200880021552A CN 101687908 B CN101687908 B CN 101687908B
- Authority
- CN
- China
- Prior art keywords
- cit
- antibody
- people
- antigen
- cys
- 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.)
- Expired - Fee Related
Links
- 206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 215
- 239000000427 antigen Substances 0.000 title claims abstract description 107
- 108091007433 antigens Proteins 0.000 title claims abstract description 107
- 102000036639 antigens Human genes 0.000 title claims abstract description 107
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 86
- 230000000890 antigenic effect Effects 0.000 claims description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 27
- 238000012360 testing method Methods 0.000 claims description 25
- 238000001514 detection method Methods 0.000 claims description 18
- 238000003745 diagnosis Methods 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 230000008878 coupling Effects 0.000 claims description 7
- 238000010168 coupling process Methods 0.000 claims description 7
- 238000005859 coupling reaction Methods 0.000 claims description 7
- 230000004048 modification Effects 0.000 claims description 6
- 238000012986 modification Methods 0.000 claims description 6
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 239000012472 biological sample Substances 0.000 claims description 4
- 230000021736 acetylation Effects 0.000 claims description 2
- 238000006640 acetylation reaction Methods 0.000 claims description 2
- 230000012447 hatching Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000008157 ELISA kit Methods 0.000 claims 1
- 201000003068 rheumatic fever Diseases 0.000 claims 1
- 238000009008 sandwich enzyme-linked immunosorbent assay kity Methods 0.000 claims 1
- 238000003375 selectivity assay Methods 0.000 claims 1
- 210000002966 serum Anatomy 0.000 abstract description 50
- 125000000217 alkyl group Chemical group 0.000 abstract description 9
- 239000001257 hydrogen Substances 0.000 abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 8
- 125000002252 acyl group Chemical group 0.000 abstract description 7
- 125000003396 thiol group Chemical class [H]S* 0.000 abstract description 7
- 108010016626 Dipeptides Proteins 0.000 abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 5
- 229960002173 citrulline Drugs 0.000 description 54
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 41
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 39
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 39
- 235000013477 citrulline Nutrition 0.000 description 39
- 235000018102 proteins Nutrition 0.000 description 35
- 108090000623 proteins and genes Proteins 0.000 description 35
- 102000004169 proteins and genes Human genes 0.000 description 35
- 229940024606 amino acid Drugs 0.000 description 34
- 238000011282 treatment Methods 0.000 description 33
- 102100025721 Cytosolic carboxypeptidase 2 Human genes 0.000 description 29
- 101000932634 Homo sapiens Cytosolic carboxypeptidase 2 Proteins 0.000 description 29
- 101001033011 Mus musculus Granzyme C Proteins 0.000 description 29
- 235000001014 amino acid Nutrition 0.000 description 29
- 238000000034 method Methods 0.000 description 27
- 150000001413 amino acids Chemical class 0.000 description 25
- 201000010099 disease Diseases 0.000 description 21
- 125000000539 amino acid group Chemical group 0.000 description 18
- 230000035945 sensitivity Effects 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 239000012491 analyte Substances 0.000 description 16
- 238000002965 ELISA Methods 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 108010076039 Polyproteins Proteins 0.000 description 13
- 239000013256 coordination polymer Substances 0.000 description 13
- 230000009260 cross reactivity Effects 0.000 description 13
- 210000003719 b-lymphocyte Anatomy 0.000 description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 208000023275 Autoimmune disease Diseases 0.000 description 8
- 206010003246 arthritis Diseases 0.000 description 8
- 238000013507 mapping Methods 0.000 description 8
- 230000004481 post-translational protein modification Effects 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 230000009257 reactivity Effects 0.000 description 8
- 108091000520 Protein-Arginine Deiminase Type 4 Proteins 0.000 description 7
- 230000005847 immunogenicity Effects 0.000 description 7
- 150000007970 thio esters Chemical class 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 108091092195 Intron Proteins 0.000 description 6
- 102000037106 Protein-Arginine Deiminase Type 4 Human genes 0.000 description 6
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- 230000001717 pathogenic effect Effects 0.000 description 6
- -1 peptidyl arginine Chemical compound 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 206010060820 Joint injury Diseases 0.000 description 5
- 125000003368 amide group Chemical group 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000000835 fiber Substances 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 206010001488 Aggression Diseases 0.000 description 4
- 101710155594 Coiled-coil domain-containing protein 115 Proteins 0.000 description 4
- 102100035027 Cytosolic carboxypeptidase 1 Human genes 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- 102100040485 HLA class II histocompatibility antigen, DRB1 beta chain Human genes 0.000 description 4
- 108010039343 HLA-DRB1 Chains Proteins 0.000 description 4
- 102100040247 Tumor necrosis factor Human genes 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 125000003275 alpha amino acid group Chemical class 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 210000000845 cartilage Anatomy 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 125000006850 spacer group Chemical group 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 102100032752 C-reactive protein Human genes 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000011782 Keratins Human genes 0.000 description 3
- 108010076876 Keratins Proteins 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 206010039361 Sacroiliitis Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000006472 autoimmune response Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 3
- 102000005525 fibrillarin Human genes 0.000 description 3
- 108020002231 fibrillarin Proteins 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 150000002466 imines Chemical class 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002045 lasting effect Effects 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000008521 reorganization Effects 0.000 description 3
- 229960004641 rituximab Drugs 0.000 description 3
- 210000005222 synovial tissue Anatomy 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 0 CC(NN(C)N)O*(*)P Chemical compound CC(NN(C)N)O*(*)P 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102000005600 Cathepsins Human genes 0.000 description 2
- 108010084457 Cathepsins Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 108010008165 Etanercept Proteins 0.000 description 2
- 102100026671 F-actin-capping protein subunit alpha-1 Human genes 0.000 description 2
- 101710087984 F-actin-capping protein subunit alpha-1 Proteins 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- 102100022678 Nucleophosmin Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010036030 Polyarthritis Diseases 0.000 description 2
- 102000006010 Protein Disulfide-Isomerase Human genes 0.000 description 2
- 108091000521 Protein-Arginine Deiminase Type 2 Proteins 0.000 description 2
- 102100035735 Protein-arginine deiminase type-2 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102100035071 Vimentin Human genes 0.000 description 2
- 108010065472 Vimentin Proteins 0.000 description 2
- 229960002964 adalimumab Drugs 0.000 description 2
- 108010081577 aldehyde dehydrogenase (NAD(P)+) Proteins 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000013024 dilution buffer Substances 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 229960000403 etanercept Drugs 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 230000001723 fibrinogenic effect Effects 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- ZTVZLYBCZNMWCF-UHFFFAOYSA-N homocystine Chemical compound [O-]C(=O)C([NH3+])CCSSCCC([NH3+])C([O-])=O ZTVZLYBCZNMWCF-UHFFFAOYSA-N 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229960000598 infliximab Drugs 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000000474 nursing effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 125000001151 peptidyl group Chemical group 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229930029653 phosphoenolpyruvate Natural products 0.000 description 2
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 108020003519 protein disulfide isomerase Proteins 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 239000013037 reversible inhibitor Substances 0.000 description 2
- 229940061969 rheumatrex Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000001258 synovial membrane Anatomy 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 210000005048 vimentin Anatomy 0.000 description 2
- OIXLLKLZKCBCPS-RZVRUWJTSA-N (2s)-2-azanyl-5-[bis(azanyl)methylideneamino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.OC(=O)[C@@H](N)CCCNC(N)=N OIXLLKLZKCBCPS-RZVRUWJTSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000008190 Agammaglobulinemia Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101710117545 C protein Proteins 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 102000003908 Cathepsin D Human genes 0.000 description 1
- 108090000258 Cathepsin D Proteins 0.000 description 1
- 241000218631 Coniferophyta Species 0.000 description 1
- 241000949473 Correa Species 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010008655 Epstein-Barr Virus Nuclear Antigens Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010064885 HLA-DR3 Antigen Proteins 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- 101001100327 Homo sapiens RNA-binding protein 45 Proteins 0.000 description 1
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZUKPVRWZDMRIEO-VKHMYHEASA-N L-cysteinylglycine Chemical compound SC[C@H]([NH3+])C(=O)NCC([O-])=O ZUKPVRWZDMRIEO-VKHMYHEASA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
- 108010025568 Nucleophosmin Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241001111421 Pannus Species 0.000 description 1
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 1
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 102100038823 RNA-binding protein 45 Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 206010061363 Skeletal injury Diseases 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 108010008038 Synthetic Vaccines Proteins 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 239000006035 Tryptophane Substances 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000002160 alpha blocker Substances 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003456 anti-perinuclear Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229940009100 aurothiomalate Drugs 0.000 description 1
- XJHSMFDIQHVMCY-UHFFFAOYSA-M aurothiomalic acid Chemical compound OC(=O)CC(S[Au])C(O)=O XJHSMFDIQHVMCY-UHFFFAOYSA-M 0.000 description 1
- 210000000649 b-lymphocyte subset Anatomy 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000003570 biosynthesizing effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 108010016616 cysteinylglycine Proteins 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000007435 diagnostic evaluation Methods 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000000937 inactivator Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 239000013038 irreversible inhibitor Substances 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000001806 memory b lymphocyte Anatomy 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 201000002674 obstructive nephropathy Diseases 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000009295 sperm incapacitation Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Rheumatology (AREA)
- Cell Biology (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rehabilitation Therapy (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Public Health (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
捕获抗原 | RA血清(%)(n=55) | 对照血清(%)(n=28) |
CCP2 | 67 | 0 |
CitD1 | 89 | 0 |
CitD2 | 98 | 0 |
Claims (10)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/767,775 | 2007-06-25 | ||
US11/767,775 US8323656B2 (en) | 2007-06-25 | 2007-06-25 | Antigen determinant of rheumatoid arthritis-specific autoantibody and use thereof |
PCT/CA2008/001193 WO2009000077A1 (en) | 2007-06-25 | 2008-06-23 | Antigen determinant of rheumatoid arthritis-specific autoantibody and use thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101687908A CN101687908A (zh) | 2010-03-31 |
CN101687908B true CN101687908B (zh) | 2013-09-04 |
Family
ID=40137119
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2008800215523A Expired - Fee Related CN101687908B (zh) | 2007-06-25 | 2008-06-23 | 类风湿性关节炎特异性自身抗体的抗原决定簇及其用途 |
Country Status (3)
Country | Link |
---|---|
US (1) | US8323656B2 (zh) |
CN (1) | CN101687908B (zh) |
WO (1) | WO2009000077A1 (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7834140B2 (en) | 2006-10-12 | 2010-11-16 | Saint Louis University | Polypeptide fragment of constitutive coactivator of PPARgamma |
CN101819201B (zh) * | 2009-03-20 | 2013-06-19 | 上海荣盛生物药业有限公司 | 用于类风湿关节炎免疫抗体体外检测的多肽组合物 |
US9140701B2 (en) * | 2009-08-18 | 2015-09-22 | The Board Of Trustees Of The Leland Stanford Junior University | Fibrinogen immune complexes to diagnose and guide therapy in rheumatoid arthritis |
EP2325195A1 (en) | 2009-11-23 | 2011-05-25 | Toscana Biomarkers S.r.l. | Viral citrullinated peptides and uses thereof |
EP2402368A1 (en) | 2010-07-02 | 2012-01-04 | Toscana Biomarkers S.r.l. | Histone citrullinated peptides and uses thereof |
JP6154748B2 (ja) * | 2011-02-02 | 2017-06-28 | アカデミス ズィーケンハイス レイデン ハー.オー.デー.エン. エルユーエムセー | 抗カルバミル化タンパク質抗体及び関節炎リスク |
EP2527841A1 (en) | 2011-05-25 | 2012-11-28 | Toscana Biomarkers S.r.l. | Methods for the diagnosis of rheumatoid arthritis |
CN106950365B (zh) * | 2017-02-15 | 2018-11-27 | 中国医学科学院北京协和医院 | 一种acpa阴性的ra诊断标志物及其应用 |
CN112924673A (zh) * | 2021-01-28 | 2021-06-08 | 中国医学科学院北京协和医院 | 一种用于诊断类风湿关节炎合并肺间质纤维化的生物标志物及其用途 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001046222A3 (en) * | 1999-12-21 | 2002-01-17 | Innogenetics Nv | Peptides designed for the diagnosis and treatment of rheumatoid arthritis |
WO2004078098A2 (en) * | 2003-03-07 | 2004-09-16 | London Health Sciences Centre Research Inc. | Peptides associated with hla-dr mhc class ii molecules involved in autoimmune diseases |
CN1575184A (zh) * | 2001-09-07 | 2005-02-02 | 波士顿大学理事会 | 治疗免疫复合物相关疾病的方法和组合物 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992019649A1 (fr) * | 1991-04-26 | 1992-11-12 | Clonatec | Antigenes reconnus par des anticorps de la polyarthrite rhumatoide, leur preparation et leurs applications |
NL1004539C2 (nl) * | 1996-11-15 | 1998-05-20 | Stichting Tech Wetenschapp | Peptide afgeleid van een door auto-antilichamen van patiënten met reumatoïde artritis herkend antigeen, antilichaam daartegen en werkwijze voor het detecteren van auto-immuunantilichamen. |
FR2795735B1 (fr) * | 1999-07-01 | 2001-09-07 | Univ Toulouse | Derives citrullines de la fibrine et leur utilisation pour le diagnostic ou le traitement de la polyarthrite rhumatoide |
AU2003261723A1 (en) | 2002-08-27 | 2004-03-19 | Takeda Chemical Industries, Ltd. | Cxcr4 antagonist and use thereof |
-
2007
- 2007-06-25 US US11/767,775 patent/US8323656B2/en not_active Expired - Fee Related
-
2008
- 2008-06-23 WO PCT/CA2008/001193 patent/WO2009000077A1/en active Application Filing
- 2008-06-23 CN CN2008800215523A patent/CN101687908B/zh not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001046222A3 (en) * | 1999-12-21 | 2002-01-17 | Innogenetics Nv | Peptides designed for the diagnosis and treatment of rheumatoid arthritis |
CN1575184A (zh) * | 2001-09-07 | 2005-02-02 | 波士顿大学理事会 | 治疗免疫复合物相关疾病的方法和组合物 |
WO2004078098A2 (en) * | 2003-03-07 | 2004-09-16 | London Health Sciences Centre Research Inc. | Peptides associated with hla-dr mhc class ii molecules involved in autoimmune diseases |
Also Published As
Publication number | Publication date |
---|---|
US8323656B2 (en) | 2012-12-04 |
CN101687908A (zh) | 2010-03-31 |
WO2009000077A1 (en) | 2008-12-31 |
US20080318872A1 (en) | 2008-12-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101687908B (zh) | 类风湿性关节炎特异性自身抗体的抗原决定簇及其用途 | |
CN101952313B (zh) | 14‑3‑3η抗体及其用于诊断和治疗关节炎的用途 | |
US20160153983A1 (en) | Biomarkers, methods and kits for the diagnosis of rheumatoid arthritis | |
Sordet et al. | Contribution of autoantibodies to the diagnosis and nosology of inflammatory muscle disease | |
van Beers et al. | Anti-citrullinated fibronectin antibodies in rheumatoid arthritis are associated with human leukocyte antigen-DRB1 shared epitope alleles | |
JP2013032358A (ja) | リウマチ疾患の診断方法 | |
BR122013006960A2 (pt) | Peptídeo sintético que é imunologicamente reativo com um anticorpo de proteína anti-citrulinado, seu uso e seu método de identificação, bem como kit compreendendo o referido peptídeo | |
Elli et al. | Immunological effects of transglutaminase-treated gluten in coeliac disease | |
JP6756611B2 (ja) | 中和抗体を検出するための競合リガンド結合アッセイ | |
JP2011521216A (ja) | 関節リウマチの診断のための方法およびキット | |
Trier et al. | Physical characteristics of a citrullinated pro-filaggrin epitope recognized by anti-citrullinated protein antibodies in rheumatoid arthritis sera | |
CN113287013A (zh) | 溃疡性大肠炎以及原发性硬化性胆管炎的检查方法 | |
Viljanen et al. | Synthesis of an array of triple-helical peptides from type II collagen for multiplex analysis of autoantibodies in rheumatoid arthritis | |
Hirose et al. | Increase in acrolein-conjugated immunoglobulins in saliva from patients with primary Sjögren's syndrome | |
CN108948153A (zh) | 一种瓜氨酸修饰肽抗原组合及其应用 | |
EP3215847A1 (en) | Pif binding as a marker for immune dysregulation | |
AU2015218355B2 (en) | Acetaminophen protein adducts and methods of use thereof | |
US20230013244A1 (en) | Pif binding as a marker for immune dysregulation | |
DK2671084T3 (en) | Biomarkers for osteoarthritis | |
Wolf et al. | Quantification of human tissue transglutaminase by a luminescence sandwich enzyme-linked immunosorbent assay | |
Choi et al. | Clinical significance of anti-filaggrin antibody recognizing uncitrullinated filaggrin in rheumatoid arthritis | |
JP2014162772A (ja) | 抗シトルリン化タンパクヒトIgG抗体およびその用途 | |
CN107484423A (zh) | 通过测量抗ccp和抗pik3cd来评估类风湿性关节炎的方法 | |
JP6315832B2 (ja) | 非特異的間質性肺炎の診断のためのバイオマーカー | |
JP2018501238A (ja) | 合成ビエピトープ化合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: WUXI JCANTEK PHARMACEUTICALS TECHNOLOGY CO., LTD. Free format text: FORMER OWNER: XU YIJUN Effective date: 20140317 |
|
C41 | Transfer of patent application or patent right or utility model | ||
COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; TO: 214174 WUXI, JIANGSU PROVINCE |
|
TR01 | Transfer of patent right |
Effective date of registration: 20140317 Address after: 214174 No. 1608, Huishan Avenue, Wuxi, Jiangsu Patentee after: Wuxi Jcantek Pharmaceuticals Ltd. Address before: Ontario, Canada Patentee before: Xu Yijun |
|
TR01 | Transfer of patent right |
Effective date of registration: 20211025 Address after: No. 381-8, Zhenghe Avenue, Huigu entrepreneurship Park, Huishan Economic Development Zone, Wuxi, Jiangsu 214000 Patentee after: Wuxi Pinyuan Technology Consulting Co.,Ltd. Address before: 214174 No. 1608, Huishan Avenue, Wuxi, Jiangsu Patentee before: WUXI JCANTEK PHARMACEUTICALS Ltd. |
|
TR01 | Transfer of patent right | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130904 |
|
CF01 | Termination of patent right due to non-payment of annual fee |