LINKAGE OF RHEUMATOID-ARTHRITIS WITH HLA

Objective-To determine whether HLA exerts a variable influence on the predisposition of siblings of probands with clinically mild and severe rheumatoid arthritis (RA). Method-Calculation of crude and adjusted o dds ratios for concordance rates in sibships sharing two, one and no H LA haplotypes with a proband with clinically mild and severe RA, and H LA haplotype sharing in multiply affected sibships in the same clinica l groups. Results-Compared with a reference value of 1.0 in siblings s haring no HLA haplotypes with a proband with mild RA, siblings sharing two HLA haplotypes with a severely affected proband had a sibship con cordance rate odds ratio of 9.7 (95% confidence interval 2.5 to 38.2). When adjusted for age, sex, and disease duration, the odds ratio was 7.6 (1.8 to 32-4). No other sibships showed concordance rates which we re significantly higher than the reference group. HLA haplotype sharin g in multiply affected sibships in which the proband had severe RA dev iated significantly from random (two, one, and no HLA haplotypes share d: 53.3, 40, and 6.7%, respectively; expected 25, SO, and 25%), wherea s in sibships of probands with mild RA they did not (14.6, 70.8, and 1 4.6%). Conclusions-In the predisposition of siblings to RA, sharing HL A haplotypes with a proband is only important if the proband has sever e RA. Mild RA is not genetically linked to the HLA region.