Association of HLA-DR3 with anti-cyclic citrullinated peptide antibody-negative rheumatoid arthritis.

Abstract

OBJECTIVE:

Recent data have shown that the most prominent and longest known genetic risk factors for rheumatoid arthritis (RA), HLA-DRB1 shared epitope alleles, are only associated with RA that is characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP antibodies) and not with anti-CCP-negative RA. We undertook this study to investigate whether anti-CCP-negative RA is associated with other HLA-DRB1 alleles.

METHODS:

HLA typing was performed for 377 patients from the Leiden Early Arthritis Clinic who were diagnosed as having RA within the first year of followup (206 anti-CCP-positive patients and 171 anti-CCP-negative patients), 235 patients who, after 1 year, had undifferentiated arthritis (UA) (28 anti-CCP-positive patients and 207 anti-CCP-negative patients), and 423 healthy control subjects. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for HLA-DRB1 allele frequencies were determined for all patient groups compared with the healthy control group.

RESULTS:

HLA-DR3 was more frequently present in the anti-CCP-negative RA group than in the control group (OR 1.84, 95% CI 1.26-2.67). This was not the case for anti-CCP-positive RA (OR 0.92, 95% CI 0.60-1.40). HLA-DR3 was also more frequently present in anti-CCP-negative UA patients (OR 1.59, 95% CI 1.10-2.28), but not in anti-CCP-positive UA patients (OR 0.68, 95% CI 0.17-1.92).

CONCLUSION:

HLA-DR3 is associated with anti-CCP-negative arthritis and not with anti-CCP-positive arthritis. These data show that distinct genetic risk factors are associated with the presence of anti-CCP antibodies in RA and indicate that different pathogenetic mechanisms underlie anti-CCP-positive and anti-CCP-negative RA.

• Authors: Kirsten N Verpoort, Floris A van Gaalen, Annette H M van der Helm-van Mil, Geziena M T Schreuder, Ferdinand C Breedveld, Tom W J Huizinga, Rene R P de Vries, Rene E M Toes
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 52 Issue 10 Pg. 3058-62 (Oct 2005) ISSN: 0004-3591 [Print] United States
• PMID: 16200610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• HLA-DR3 Antigen
• Peptides, Cyclic
• cyclic citrullinated peptide

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Arthritis, Rheumatoid (epidemiology, genetics, immunology)
• Autoantibodies
• Female
• Gene Frequency
• HLA-DR3 Antigen (genetics)
• Humans
• Male
• Middle Aged
• Peptides, Cyclic (immunology)
• Risk Factors