HLA: linkage with rheumatoid arthritis or seropositivity

HLA haplotype sharing was compared in sibships from multicase families with rheumatoid arthritis (RA), subdivided by rheumatoid factor status, to investigate the claim that HLA is linked more to RA severity than susceptibility. Considerable deviation from expected (Mendelian) inheritance towards greater sharing of inherited parental haplotypes was observed in the sibships as a whole and when subdivided according to the serological status of the sibship's members. Further, there was no evidence that linkage was stronger in the seropositive concordant than in the other sibships. Linkage was also demonstrated between HLA and seropositivity even in sibships where not all members expressed clinical RA. These results, therefore, do not support the existence of genetic heterogeneity between seropositive and seronegative RA, a possibility previously suggested from population studies of antigen associations.