Distinct ACPA fine specificities, formed under the influence of HLA shared epitope alleles, have no effect on radiographic joint damage in rheumatoid arthritis.

Abstract:

OBJECTIVES:Human leucocyte antigen shared epitope (SE) alleles are associated with joint destruction, the presence of anticitrullinated protein antibodies (ACPA) and the ACPA fine specificity repertoire in rheumatoid arthritis (RA). A large variation in joint destruction is seen within the ACPA-positive patient population, and it is conceivable that certain ACPA reactivities contribute to radiological damage. The authors investigated whether ACPA fine specificities, which are formed under the influence of SE alleles, associate with the extent of radiographic joint damage. METHODS:Antibodies recognising six citrullinated epitopes were determined in sera of 330 ACPA-positive RA patients genotyped for SE alleles. The association between SE alleles, ACPA fine specificity and radiographic joint damage was assessed using radiographic follow-up data. A second cohort of 154 RA patients with 5 and 10-year radiographic follow-up was used for replication. RESULTS:SE alleles predisposed to the recognition of certain citrullinated epitopes. However, none of the ACPA fine specificities studied influenced radiographic joint damage. Importantly, although SE alleles associated with radiographic damage in the total RA population, this association was no longer detectable after stratification for the presence of ACPA. CONCLUSIONS:SE alleles are instrumental in shaping the ACPA repertoire. However, ACPA fine specificities formed under the influence of SE alleles do not seem to affect joint destruction.

journal_name

Ann Rheum Dis

authors

Scherer HU,van der Woude D,Willemze A,Trouw LA,Knevel R,Syversen SW,van der Linden MP,Lie B,Huizinga TW,van der Heijde DM,van der Helm-van Mil AH,Kvien TK,Toes RE

doi

10.1136/ard.2010.146506

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

1461-4

issue

8

eissn

0003-4967

issn

1468-2060

pii

ard.2010.146506

journal_volume

70

pub_type

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