Effect of Rheumatoid Arthritis (RA) Susceptibility Genes on the Immune Response to Viral Citrullinated Peptides in RA

Abstract

To the Editor: Anticitrullinated peptide/protein antibodies (ACPA) are a family of rheumatoid arthritis (RA)-specific antibodies that recognize various protein sequences containing citrulline, the deiminated form of arginine produced posttranslationally by peptidylarginine deiminase (PAD) enzymes. Recently, viral citrullinated peptides (VCP) derived from Epstein-Barr virus nuclear proteins EBNA-1 and EBNA-2 have been described as a target of ACPA in RA sera1,2. Genetic factors predisposing to RA, namely HLA-DRB1 shared epitope (SE) alleles and PTPN22 gene variants, as well as the TRAF1/C5 locus and PADI4 susceptible haplotype, have been found to be predominantly associated with ACPA-positive RA, even if the association with ACPA-negative RA cannot be excluded. We evaluated the influence of genes conferring susceptibility to RA on the production of anti-VCP antibodies and tested the interaction of VCP with HLA in vitro . We analyzed 172 patients with RA of French white origin3. All provided informed consent and the Ethics Committee of Hopital Bicetre (AP-HP, Paris, France) approved the study. HLA-DRB1 typing and subtyping were performed by a polymerase chain reaction (PCR)-based method, using a panel of sequence-specific oligonucleotide probes. PADI4 haplotypes were obtained by typing 3 single-nucleotide polymorphisms (SNP: rs1886303, PADI4\_92, PADI4\_96 – CGC haplotype) by PCR-restriction fragment-length polymorphism (RFLP)4. PTPN22 (R620W; rs24766601 – T variant) and C5/TRAF1 region polymorphisms (rs10818488 – A variant) were genotyped by PCR-RFLP5,6. … Address correspondence to Dr. P. Migliorini; E-mail: paola.migliorini{at}med.unipi.it