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A standardized cell surface antibody assay was used to measure binding of circulating human immunoglobulins to rat or piglet splenocytes. In 100-fold diluted serum fractions, lymphocyte surface antibodies were detected in 30% of Type 1 (insulin-dependent) diabetic patients under 20 years of age but in none of 33 control subjects. Binding occurred with T and B lymphocytes, appeared unrelated to Fc receptors or protein glycosylation and was not attributable to insulin or albumin antibodies. At clinical onset of the disease, the lymphocyte surface antibodies belonged primarily to the IgM-class. Their presence was positively correlated to that of IgM-pituitary cell surface antibodies and their absorption by anterior pituitary cells occurred as well as by splenocytes. Lymphocyte surface antibodies remained present during the first years of insulin treatment. They were also detected in first degree relatives of lymphocyte surface antibody-positive patients. It is unlikely that IgM-lymphocyte surface antibodies mark the destructive process in the pancreatic B cell population. They may, instead, express a state of immune reactivity which precedes the formation of IgG-autoantibodies and therefore be associated with an event in the development of diseases such as Type 1 (insulin-dependent) diabetes. [ABSTRACT FROM AUTHOR]

A standardized method has been developed for the assay of cell surface antibodies in IgM- and IgG-fractions from human serum. Suspensions of adult rat islet B cells, islet non-B cells, and anterior pituitary cells were used as antigen source and a cell sorter as analyser of the immunoglobulin binding to individual cells. Assay conditions were selected wherein no surface antibodies were detected in 33 control subjects younger than 20 years. In 30% of Type 1 (insulin-dependent) diabetic patients, surface antibodies were measured with rat anterior pituitary cells as well as with rat islet B cells. Binding to pituitary cells occurred with IgM- and IgG-fractions and correlated positively with IgG binding to islet B cells. At onset of the disease, the prevalence of IgM-rat anterior pituitary cell surface antibodies was higher than that of IgG-rat anterior pituitary cell surface antibodies. Cell surface antibodies were also detected in first-degree relatives of Type 1 diabetic patients, but corresponded primarily to IgM-rat anterior pituitary cell surface antibodies. It is concluded that the development of Type 1 diabetes in subjects younger than 20 years is associated with the generation of both IgM and IgG cell surface antibodies. The IgM surface antibodies may result from stimulated production of polyreactive natural autoantibodies and could precede the switch to the formation of monoreactive IgG autoantibodies. The assay of IgM cell surface antibodies can be useful in studies on the sequence of immune events in diabetes and other autoimmune disease. [ABSTRACT FROM AUTHOR]