Comparison of DNA antibody idiotypes in human sera: an international collaborative study of 19 idiotypes from 11 different laboratories

The distribution of and relationships between 18 anti-DNA antibody idiotypes and one anti-acetylcholine receptor antibody idiotype have been tested in an international collaborative study of human sera from 180 individuals. The main finding is that the serum levels of many of these idiotypes, whether of murine or human origin, show a high degree of statistical correlation. The studies in a wide range of autoimmune rheumatic diseases confirm that none of the idiotypes tested is disease specific, but 13 of 15 (87%) whose levels were recorded as OD units or cpm correlated strongly with anti-ssDNA antibody levels and 11 of 15 (73%) with total serum IgM. Expression of several idiotypes was found to fluctuate in parallel with disease activity in SLE; levels of others were also elevated in the healthy relatives of lupus patients whilst a few were also raised in the spouses of these patients. The data support the notion that there may be only a few groups of related DNA antibody idiotypes. The correlations between the idiotypes with regard to their quantities, association with disease activity, and wide distribution in different diseases and healthy individuals suggest at least two explanations. First, all of these idiotypes may be present in normal immunoglobulin repertoires and simply increase in response to poly- or oligoclonal B-cell activation in autoimmune diseases. Secondly, these idiotypes may be structurally linked to each other, so that their behaviour under conditions of specific antigenic stimulation is similar. Genetic and structural studies will be required to distinguish between these possibilities.