Antibodies to type II collagen and HLA disease susceptibility markers in rheumatoid arthritis

Autor: Andrew D. Cook, A Stockman, K. D. Muirden, Claude C.A. Bernard, Merrill J. Rowley, Ian R. Mackay, Brian D. Tait, Caroline Brand
Rok vydání: 1999
Předmět:
Zdroj: Arthritis & Rheumatism. 42:2569-2576
ISSN: 1529-0131
0004-3591
DOI: 10.1002/1529-0131(199912)42:12<2569::aid-anr9>3.0.co;2-3
Popis: Objective. To seek associations between antibodies to native and denatured type II collagen (NCII and DCII) and HLA in rheumatoid arthritis (RA). Methods. One hundred fourteen patients with clinically well-defined RA were HLA‐DR and DQ typed. Those who were DR4 positive were subtyped for DRB1*0401‐*0408 alleles by polymerase chain reaction using allele-specific oligonucleotide probes. Antibodies to human NCII and DCII (heat-denatured) were measured by enzyme-linked immunosorbent assay. The frequency of HLA alleles was compared in patients grouped according to the presence and absence of antibodies to NCII and DCII. Results. Twenty-seven patients (24%) were positive for antibodies to NCII. There was a significant increase in the frequency of HLA‐DR7 in anti-NCII‐ positive patients compared with anti-NCII‐negative patients (30% versus 9%; P 5 0.019) and a significant decrease in HLA‐DR3 (7% versus 28%; P 5 0.044). Repeating the analyses after excluding the 16 patients who were DR7 positive revealed a significant increase in the frequency of HLA‐DR1 in anti-NCII‐positive patients compared with anti-NCII‐negative patients (63% versus 27%; P 5 0.045). Moreover, antibodies to NCII were associated with the third hypervariability region susceptibility sequence QRRAA that is present in DRB1*0101, *0404, *0405, and *0408 (84% versus 47%; P 5 0.0085); 24 of 27 anti-NCII‐positive patients were positive for either DR7, DR1, or DRB1*0404 or *0408. Thirty patients (26%) were positive for antibodies to DCII. There was a significant increase in the frequency of HLA‐DR3 in anti-DCII‐positive patients compared with anti-DCII‐negative patients (40% versus 18%; P 5 0.028). Conclusion. The genetic associations between HLA‐DR alleles and antibodies to CII in RA patients is in keeping with the collagen-induced arthritis model and implicates autoimmunity to CII as a major component in the multifactorial pathogenesis of RA.
Databáze: OpenAIRE
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