HLA-LINKED SUSCEPTIBILITY TO RHEUMATOID-ARTHRITIS - A STUDY OF 41 MULTICASE FAMILIES FROM NORTHERN INDIA

Objective. To analyze segregation of rheumatoid arthritis (RA) with HL A-DR4 and/or other alleles in multicase RA families and to compare the segregation patterns among affected and unaffected sibs. Methods. For ty-one multicase families (22 multiplex and 19 simplex) of northern In dian origin were studied for HLA haplotype segregation. Results. HLA h aplotype sharing among affected sibs was observed more often than expe cted in families in which both parents were healthy (P < 0.05). RA cos egregated with a DR4 haplotype among offspring only in multiplex famil ies in which both parents were unaffected (P < 0.05), while in simplex families, the disease segregated with DR4 only when the allele was fr om the affected DR4-heterozygous parent. In DR4-negative affected sib pairs, DR1, DR6, and DR10 were inherited from healthy parents more oft en than expected. Conclusion. Dissimilar modes of inheritance are seen among multiplex and simplex RA families. The results of segregation a nalysis are compatible with the hypothesis that an epitope, rather tha n an individual DR antigen(s), is responsible for increased risk for d evelopment of RA.