OBJECTIVE: To investigate the association of a recently described classification of Human leukocyte antigen (HLA)-DRB1 shared epitope alleles with rheumatoid factors (RF) and anti-cyclic citrullinated peptide (CCP) production and radiological severity in rheumatoid arthritis (RA). METHODS: Patients with RA (n = 962) were studied. Genotyping of DRB1 alleles and assays for RF and anti-CCP were performed. Radiological severity was measured using the modified Larsen score. RESULTS: In accordance with previous reports, we found carriage of S2 alleles (K-R-A-A at positions 71-74) to be associated with more severe disease with a gene-dose effect (p = 0.0059), and also associated with the presence of anti-CCP and RF (p<0.001). Carriage of S1 alleles (D-E-R-A-A at positions 70-74) was associated with less severe disease (p = 0.01), however there was no association between S1 and either anti-CCP or RF, suggesting that the basis for this possible protective effect was not related to autoantibody-producing B cells. CONCLUSIONS: These data suggest that multiple biological mechanisms underlie the DRB1 association with rheumatoid arthritis severity.
OBJECTIVE: To investigate the association of a recently described classification of Human leukocyte antigen (HLA)-DRB1 shared epitope alleles with rheumatoid factors (RF) and anti-cyclic citrullinated peptide (CCP) production and radiological severity in rheumatoid arthritis (RA). METHODS:Patients with RA (n = 962) were studied. Genotyping of DRB1 alleles and assays for RF and anti-CCP were performed. Radiological severity was measured using the modified Larsen score. RESULTS: In accordance with previous reports, we found carriage of S2 alleles (K-R-A-A at positions 71-74) to be associated with more severe disease with a gene-dose effect (p = 0.0059), and also associated with the presence of anti-CCP and RF (p<0.001). Carriage of S1 alleles (D-E-R-A-A at positions 70-74) was associated with less severe disease (p = 0.01), however there was no association between S1 and either anti-CCP or RF, suggesting that the basis for this possible protective effect was not related to autoantibody-producing B cells. CONCLUSIONS: These data suggest that multiple biological mechanisms underlie the DRB1 association with rheumatoid arthritis severity.
Authors: Munitta Muthana; Sarah Hawtree; Adam Wilshaw; Eimear Linehan; Hannah Roberts; Sachin Khetan; Gbadebo Adeleke; Fiona Wright; Mohammed Akil; Ursula Fearon; Douglas Veale; Barbara Ciani; Anthony G Wilson Journal: Proc Natl Acad Sci U S A Date: 2015-08-27 Impact factor: 11.205
Authors: Ian C Scott; Frühling Rijsdijk; Jemma Walker; Jelmar Quist; Sarah L Spain; Rachael Tan; Sophia Steer; Yukinori Okada; Soumya Raychaudhuri; Andrew P Cope; Cathryn M Lewis Journal: J Rheumatol Date: 2015-05-15 Impact factor: 4.666