Rheumatoid arthritis in Tlingit Indians: clinical characterization and HLA associations

To characterize the features of rheumatoid arthritis (RA) in Tlingit Indians, to identify the HLA-DR alleles associated with RA in the Tlingit, and to determine whether disease severity or specific clinical manifestations correlate with the presence of specific HLA antigens.

Thirty-seven Tlingit patients with RA and 75 controls were evaluated clinically; comparative HLA studies were carried out in 33 patients and 62 controls.

The results of this clinical study of RA in the Tlingit confirms that the disease found in them is classical RA, characterized by an early age of onset, a high frequency of nodules, serum rheumatoid factor (RF) and antinuclear antibodies (ANA); an often severe clinical course, with a high frequency of erosive disease and frequent need for surgical joint repair, and an often positive family history. In Tlingit volunteers who did not have RA we also found an increased prevalence of RF and ANA. Neither HLA-DR1 nor DR4 was found to be associated with RA in the Tlingit. The commonest DR antigen in patients with RA was DR14. The most frequent DRB1 allele was DRB1*1402 (Dw16).

The Tlingit population had a very high frequency of the DRB1*1402 allele, which shares key sequence homology with DRB1*0401 (Dw4) and DRB1*0101 (Dw1), associated with RA in other racial groups. No correlations were found between specific HLA-DRB1 alleles or combinations of alleles and specific disease features or severity.