Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: Contrasting effects of HLA-DR3 and the shared epitope alleles
| Autor: | Michael F. Seldin, Mark H. Wener, Wentian Li, Claire Bombardier, Marlena Kern, Franak Batliwalla, Elaine F. Remmers, Lindsey A. Criswell, Elena Massarotti, Daniel L. Kastner, Michael H. Weisman, Patricia Irigoyen, Annette Lee, Peter K. Gregersen, Raymond F. Lum |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male musculoskeletal diseases medicine.medical_specialty Immunology Population HLA-DR3 Peptides Cyclic Epitope Arthritis Rheumatoid Epitopes HLA-DR3 Antigen Rheumatology immune system diseases Internal medicine Genotype medicine Humans Immunology and Allergy Rheumatoid factor Genetic Predisposition to Disease Pharmacology (medical) skin and connective tissue diseases education Alleles Autoantibodies education.field_of_study business.industry Autoantibody HLA-DR Antigens Middle Aged medicine.disease Haplotypes Rheumatoid arthritis Female business HLA-DRB1 Chains |
| Zdroj: | Arthritis & Rheumatism. 52:3813-3818 |
| ISSN: | 1529-0131 0004-3591 |
| DOI: | 10.1002/art.21419 |
| Popis: | Objective To examine the association between HLA–DRB1 alleles and the production of anti–cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) autoantibodies in patients with rheumatoid arthritis (RA). Methods We studied 1,723 Caucasian RA patients enrolled in the North American Rheumatoid Arthritis Consortium (NARAC) family cohort and the Study of New Onset Rheumatoid Arthritis (SONORA) cohort. All patients were tested for anti-CCP antibodies (by enzyme-linked immunosorbent assay), RF (by nephelometry), and HLA–DR genotype (by polymerase chain reaction and sequence-specific oligonucleotide hybridization). Results When controlled for the presence of RF, anti-CCP positivity was strongly associated with the HLA–DRB1 shared epitope (SE). In RF+ patients, the presence of the SE was very significantly associated with anti-CCP positivity, with an odds ratio (OR) of 5.8 and a 95% confidence interval (95% CI) of 4.1–8.3. This relationship was also seen in RF– patients (OR 3.1 [95% CI 1.8–5.3]). In contrast, RF positivity was not significantly associated with presence of the SE independently of anti-CCP antibodies. Strikingly, HLA–DRB1*03 was strongly associated with reduced anti-CCP titers, even after controlling for the presence of the SE and restricting the analysis to anti-CCP+ patients. HLA–DR3 was also associated with anti-CCP– RA in our population. Conclusion The HLA–DRB1 SE is strongly associated with the production of anti-CCP antibodies, but not RF. In contrast, HLA–DR3 alleles are associated with anti-CCP– disease and with lower levels of anti-CCP antibodies, even when controlling for the SE. These data emphasize the complexity of the genetic effects of the major histocompatibility complex on the RA phenotype. |
| Databáze: | OpenAIRE |
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