Monozygotic rheumatoid arthritis twin pairs express similar levels of conserved immunoglobulin V gene in polyclonal rheumatoid factors irrespective of disease status

The degree of polyclonal RF heterogeneity was assessed in diseased and non-diseased twins with rheumatoid arthritis (RA). The distribution of variable region determinants encoded by a set of immunoglobulin germline, or minimally mutated germline, genes within IgM RF, IgG RF and IgA RF isotypes was determined by ELISA using specific mouse monoclonal antibodies (MoAb) in fractionated plasma from 12 members of six monozygotic twin pairs with RA. The results reveal that at least 40% (range ~ 18-87%) of IgM RF are encoded by a small set of ~ 10 genes from the V(H)1, 3 and 4 families. Furthermore, a significant proportion of IgG RF and IgA RF (~ 30%) are also encoded by these same genes. Comparison with RF-negative fractions of immunoglobulins showed that the examined variable region determinants were overrepresented in the RF fractions. The level of expression of the variable region determinants in RF were generally similar within twins but different between unrelated twin pairs irrespective of disease status. The variability of V(H) gene usage between unrelated individuals suggests that the level of expression and regulation of the variable region determinants may be genetically regulated or influenced by common environmental factors.