Occurrence of a rheumatoid factor cross-reactive kappa light-chain idiotope in rheumatoid arthritis families

The occurrence of IgM rheumatoid factor (RF) and RF-associated kappa-III light-chain idiotope identified by monoclonal antibody 6B6.6 in the serum from 22 patients with rheumatoid arthritis (RA) and 68 relatives without connective tissue diseases in 15 families was determined by solid-phase enzyme-linked immunosorbent assays. Serum IgM RF was present in 19 RA patients from 12 families and 12 arthritis-free relatives of 4 families. It was not found in any of 9 spouses included in the study or in 44 of 45 unrelated healthy adult controls. RF-associated 6B6.6 idiotope was detected in 42% of the IgM RF(+) RA patients and in 50% of the IgM RF(+) arthritis-free relative, but not in the adult controls, spouses, and IgM RF(-) RA patients and relatives. It was present in one RA serum from each of 8 families and 6 sera from arthritis-free relatives of 2 families (5 of whom were from one family). Where present, the idiotope-positive RF represented only a small fraction of the serum IgM RF of the RA patients (0.1-2.1%) and relatives (1.5-14%). The increased frequency of IgM RF(+) individuals, with and without RA, in family groups suggests a genetic predisposition for expression of RF. The small proportion of RF bearing the 6B6.6 idiotope in both RA patients and unaffected family members supports the view that the number of germline genes encoding for RF is large or that extensive mutation occurs in the course of RF expression, whether idiopathic or associated with RA. In addition, nonuniform expression of the idiotope in RF within family groups indicates that the various clones of RF producing cells are to a large extent independently regulated.