Association between protein tyrosine phosphatase 22 variant R620W in conjunction with the HLA-DRB1 shared epitope and humoral autoimmunity to an immunodominant epitope of cartilage-specific type II collagen in early rheumatoid arthritis
(2006) In Arthritis and Rheumatism 54(1). p.82-89- Abstract
- Objective. To analyze the genetic impact of allelic variants of the protein tyrosine phosphatase N22 (PTPN22) and HLA-DRB1 alleles on IgG autoantibody formation directed toward an immunodominant conformational epitope (C1(III); amino acid residues 359-369) of type 11 collagen (CII) in early rheumatoid arthritis (RA). Methods. Sera obtained at study inclusion from an inception cohort of RA patients (n = 221; mean symptom duration 6 months) were analyzed for circulating anti-C1(III). IgG autoantibodies. An enzyme-linked immunosorbent assay based on solid-phase-coupled synthetic triple-helical collagen peptides was used to quantify Immoral autoimmune responses. HLA-DRB1 genotypes were determined by allele-specific polymerase chain reaction... (More)
- Objective. To analyze the genetic impact of allelic variants of the protein tyrosine phosphatase N22 (PTPN22) and HLA-DRB1 alleles on IgG autoantibody formation directed toward an immunodominant conformational epitope (C1(III); amino acid residues 359-369) of type 11 collagen (CII) in early rheumatoid arthritis (RA). Methods. Sera obtained at study inclusion from an inception cohort of RA patients (n = 221; mean symptom duration 6 months) were analyzed for circulating anti-C1(III). IgG autoantibodies. An enzyme-linked immunosorbent assay based on solid-phase-coupled synthetic triple-helical collagen peptides was used to quantify Immoral autoimmune responses. HLA-DRB1 genotypes were determined by allele-specific polymerase chain reaction amplification of genomic DNA and sequence-specific hybridization. PTPN22*620W genotyping was performed using an allelic discrimination TaqMan assay. Results. Anti-C1(III) IgG autoantibody titers were significantly elevated in patients with early RA as compared with those in healthy controls (n = 70). The increased titers were more pronounced in RA patients harboring alleles of the RA-associated HLA-DRB1 shared epitope (SE) consensus sequence than in those lacking the SE. In addition, the PTPN22*620W variant was strongly associated with a vigorous Immoral autoimmune response to the cartilage-specific CII determinant C1(III). Conclusion. Allelic variants encoding the binding pocket for peptide presentation (SE) to T cells and a functional domain of a negative regulator of T cell receptor signaling (PTPN22*620W), respectively, synergize in early RA to break self tolerance toward C1(III), an evolutionarily conserved cartilage determinant that is also frequently targeted in arthritogenic humoral autoimmunity in mice. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/421460
- author
- Burkhardt, H ; Huffmeier, U ; Spriewald, B ; Bohm, B ; Rau, R ; Kallert, S ; Engstrom, A ; Holmdahl, Rikard LU and Reis, A
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arthritis and Rheumatism
- volume
- 54
- issue
- 1
- pages
- 82 - 89
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:16385499
- wos:000234605200012
- scopus:31044442026
- ISSN
- 1529-0131
- DOI
- 10.1002/art.21498
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
- id
- e221687f-8dea-41c7-a1ec-151022c8dbd1 (old id 421460)
- date added to LUP
- 2016-04-01 11:55:33
- date last changed
- 2022-02-25 23:19:02
@article{e221687f-8dea-41c7-a1ec-151022c8dbd1,
abstract = {{Objective. To analyze the genetic impact of allelic variants of the protein tyrosine phosphatase N22 (PTPN22) and HLA-DRB1 alleles on IgG autoantibody formation directed toward an immunodominant conformational epitope (C1(III); amino acid residues 359-369) of type 11 collagen (CII) in early rheumatoid arthritis (RA). Methods. Sera obtained at study inclusion from an inception cohort of RA patients (n = 221; mean symptom duration 6 months) were analyzed for circulating anti-C1(III). IgG autoantibodies. An enzyme-linked immunosorbent assay based on solid-phase-coupled synthetic triple-helical collagen peptides was used to quantify Immoral autoimmune responses. HLA-DRB1 genotypes were determined by allele-specific polymerase chain reaction amplification of genomic DNA and sequence-specific hybridization. PTPN22*620W genotyping was performed using an allelic discrimination TaqMan assay. Results. Anti-C1(III) IgG autoantibody titers were significantly elevated in patients with early RA as compared with those in healthy controls (n = 70). The increased titers were more pronounced in RA patients harboring alleles of the RA-associated HLA-DRB1 shared epitope (SE) consensus sequence than in those lacking the SE. In addition, the PTPN22*620W variant was strongly associated with a vigorous Immoral autoimmune response to the cartilage-specific CII determinant C1(III). Conclusion. Allelic variants encoding the binding pocket for peptide presentation (SE) to T cells and a functional domain of a negative regulator of T cell receptor signaling (PTPN22*620W), respectively, synergize in early RA to break self tolerance toward C1(III), an evolutionarily conserved cartilage determinant that is also frequently targeted in arthritogenic humoral autoimmunity in mice.}},
author = {{Burkhardt, H and Huffmeier, U and Spriewald, B and Bohm, B and Rau, R and Kallert, S and Engstrom, A and Holmdahl, Rikard and Reis, A}},
issn = {{1529-0131}},
language = {{eng}},
number = {{1}},
pages = {{82--89}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Arthritis and Rheumatism}},
title = {{Association between protein tyrosine phosphatase 22 variant R620W in conjunction with the HLA-DRB1 shared epitope and humoral autoimmunity to an immunodominant epitope of cartilage-specific type II collagen in early rheumatoid arthritis}},
url = {{http://dx.doi.org/10.1002/art.21498}},
doi = {{10.1002/art.21498}},
volume = {{54}},
year = {{2006}},
}