RESEARCH - New classification of the shared epitope in RA: impact on the production of various anti-CCP antibodies

[Guest guest]

Rheumatology Advance Access published online on November 17, 2009

Rheumatology, doi:10.1093/rheumatology/kep338

New classification of the shared epitope in rheumatoid arthritis:

impact on the production of various anti-citrullinated protein

antibodies

Ágnes Gyetvai1, Zoltán Szekanecz2, Lilla Soós2, Zoltán Szabó2,

Fekete1, Anikó Kapitány1, Marius Teodorescu3, Sándor Sipka1, Gyula

Szegedi3 and la Lakos1,4

1Laboratory of Immunology, 3rd Department of Medicine, 2Department of

Rheumatology, Institute of Medicine, University of Debrecen Medical

and Health Science Center, 3Autoimmune Disease Research Group,

Hungarian Academy of Sciences, Debrecen, Hungary and 4TheraTest

Laboratories, Lombard, IL, USA.

Abstract

Objective. HLA-DR [shared epitope (SE)] alleles have recently been

re-classified into S1, S2, S3P and S3D groups. S2 and S3P have been

associated with increased risk for RA. We assessed the impact of S1,

S2, S3P and S3D alleles on anti-citrullinated protein antibody (ACPA)

production. Instead of comparing allele-carriers to non-carriers, we

studied each allele group individually, using the X/X (non-SE)

genotype as reference.

Methods. Serum and genomic DNA samples of 91 RA patients and 78

healthy controls were obtained. Various ACPAs and IgM RF were

determined by ELISA. HLA-DRB1 genotyping and subtyping was performed

by PCR. HLA-DRB1 alleles were re-classified as described above.

Correlations between SE and ACPAs were determined.

Results. Not only S2 and S3P, but, to a lesser extent, S1 and S3D

alleles also predisposed to anti-cyclic citrullinated peptide (CCP)

production (P < 0.0001, P = 0.004, P = 0.01 and P = 0.027,

respectively), with the following hierarchy of association: S2+S3P >

S1+S3D > X/X. Similar associations were observed for

anti-citrullinated vimentin. Anti-citrullinated fibrinogen (CF)

exerted a different association pattern with the strongest correlation

with S1 alleles [odds ratio (OR) 16.00; P = 0.05]. In addition,

HLA-DRB1*15 alleles may represent a special predisposing effect for

anti-CF antibody production. Finally, in this study, RF production was

associated only with the HLA-DRB1*0401 SE allele (P = 0.04).

Conclusions. Our approach of comparing individual S allele carriers

with X/X genotype patients allowed us to perform unequivocal analyses

and demonstrate new associations. Thus, novel subgroups of RA could be

identified with potential relevance for prognosis and therapy.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/kep338v1?papetoc

Not an MD