B lymphocyte hyperactivity in families of patients with systemic lupus erythematosus

Blood cells spontaneously secreting IgG and IgM and the level of plasma immunoglobulins and antibodies to dsDNA, ssDNA and influenza virus haemagglutinin have been determined in families of patients with SLE, in 'normal' families and groups of 'normal' individuals. IgM values were consistently higher in females than in males. About one in three of healthy blood relatives gave values in excess of the sex-matched control range in one or more of these test, particularly notable being raised values of IgG anti-dsDNA and total IgG shown by female relatives. High-scoring relatives were more likely to be offspring or parents than siblings of patients, suggesting, together with evidence from a spouse group, the involvement of environmental as well as genetic factors in these families. Correlation analysis between the various assays in the different groups showed a clear distinction between the female control group, where there were no associations, and the female relative group where there were strong associations, including a significant correlation between IgM and IgG antibodies to dsDNA. The male groups produced a more variable picture but the patients gave a remarkably consistent pattern of moderate positive associations. Pokeweed mitogen induced a higher level of IgG production in blood cells of relatives than in controls. These findings are suggestive of a breakdown in relatives of normal antibody regulation. Investigation of immunological abnormalities in family members provides a powerful tool for the analysis of a complex disease.