Immunoglobulin A and polymeric IgA rheumatoid factors in systemic sicca syndrome: partial characterization.

Sera from five patients with systemic sicca syndrome and IgA rheumatoid factors were studied to determine the levels of secretory IgA and the molecular size and subclass distribution of total serum IgA. In addition, the size distribution of the IgA rheumatoid factors was determined by isokinetic sucrose density ultracentrifugation and radioimmunoassay at neutral and acid pH. These studies revealed that 14 to 26% of total serum IgA was polymeric, whereas 64 to 85% of IgA with rheumatoid factor activity consisted of >10S polymers. The presence of polymers of IgA rheumatoid factor was confirmed by 1 ) identification of J chain, 2) binding to secretory component, 3) reduction by 2-mercaptoethanol (11 to 7S shift on sucrose density ultracentrifugation) in isolated rheumatoid factor eluates, and 4) selective transfer of polymeric IgA rheumatoid factor into rat hepatic bile. The polymeric IgA rheumatoid factors were also found to form intermediate complexes in whole serum. Elevation of total serum IgA concentration (equivalent to 150 to 470% of mean control levels) was related to a predominant increase in the IgA1 subclass, although four patients also showed some increase in lgA2 levels. A slight elevation of circulating secretory IgA was found in the two patients with the highest levels of total serum IgA. These results indicate a general perturbation of IgA metabolism in the patients studied with a selective increase in the proportion of circulating IgA polymers with rheumatoid factor activity. The polymeric nature of these antibodies provides indirect evidence for a mucosal origin of the IgA rheumatoid factor.