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Open Access Research article

Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor

Alejandro Balsa1*, Arancha Cabezón2, Gisela Orozco3, Tatiana Cobo1, Eugenia Miranda-Carus1, Miguel Ángel López-Nevot4, José Luis Vicario5, Emilio Martín-Mola1, Javier Martín3 and Dora Pascual-Salcedo2

Author Affiliations

1 Servicio de Reumatología, Hospital Universitario La Paz, Paseo de la Castellana, 261, Madrid, 28046, Spain

2 Sección de Inmunología, Hospital Universitario La Paz, Paseo de la Castellana, 261, Madrid, 28046, Spain

3 Instituto de Parasitología y Biomedicina López-Neyra, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, s/n, Armilla (Granada) 18100, Spain

4 Unidad de Inmunología, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas, 2, 18040 Granada, Spain

5 Unidad de Histocompatibilidad, Centro de Transfusión de la Comunidad de Madrid, Avda. de la Democracia, s/n. 28032 Madrid, Spain

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Arthritis Research & Therapy 2010, 12:R62  doi:10.1186/ar2975

Published: 6 April 2010

Abstract

Introduction

The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).

Methods

We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined.

Results

We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found.

Conclusions

HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.