RHEUMATOID-FACTOR ISOTYPES IN MONOZYGOTIC AND DIZYGOTIC TWINS DISCORDANT FOR RHEUMATOID-ARTHRITIS

Objective. To examine the influence of genetic factors in determining the occurrence of rheumatoid factor (RF) isotypes. We investigated the hypothesis that, in twin pairs discordant for rheumatoid arthritis (R A), a genetic influence would be indicated by a higher rate of occurre nce of RF among the unaffected monozygotic (MZ) when compared with the unaffected dizygotic (DZ) co-twins of seropositive affected twins. Me thods. IgM, IgA, and IgG RF were measured by ELISA in 70 MZ and 84 DZ disease discordant pairs using a cutoff for seropositivity defined usi ng a normal control population. The risk of seropositivity in the unaf fected twins of MZ when compared with DZ seropositive index twins was examined using odds ratios (OR). Results. For all 3 RF isotypes, level s in the unaffected twins of seropositive index twins were higher than in the control population. MZ unaffected twins showed an increased ri sk for seropositivity for IgM and IgG RF when compared with DZ unaffec ted twins: IgM OR = 2.2 (95 % CI 0.9-5.4), IgG OR = 2.4 (95 % Cl 0.9-6 .6), The greatest excess risk for seropositivity occurred for IgM RF a mongst the unaffected twin of an index twin with past or current docum ented evidence of RF seropositivity, OR = 3.4 (95 % CI 1.4-8.5). For I gA RF, seropositivity risk in MZ unaffected twins was not increased, O R = 1.0 (0.3-3.1). The seropositivity risk for all 3 isotypes was inde pendent of the age of the pair, the age of disease onset in the index twin, and the sex, HLA-DRB1O1 and DRB1*04 status of the unaffected tw in. Conclusion. Genetic factors are important in determining the level of IgM and IgG RF. A genetic contribution to RA seropositivity exists that is independent of HLA-DR.