Increased Concentrations of Total IgM At Clinical Onset of Type 1 (Insulin-Dependent) Diabetes: Correlation with IgM Binding to Cells. The Belgian Diabetes Registry

Eighty patients with type 1 (insulin-dependent) diabetes (ages 0-39 years) were consecutively recruited by the Belgian Diabetes Registry. Sera obtained at clinically diagnosed onset (i.e., before start of insulin therapy or within 7 days of initial treatment) were analyzed for total IgM concentrations and for IgM binding to fixed rat splenocytes (IgM-LyAb) and permeabilized rat islet cells (IgM-ICAb). Comparison of results with those in age- and sex-matched control subjects, by fluorescence-activated cell-sorter analysis, indicated greater concentrations of IgM-LyAb and IgM-ICAb in sera from the patients. IgM antibodies reacted indiscriminately with islet beta and islet endocrine non-beta cells. The prevalence of IgM-ICAb, but not of IgM-LyAB, was significantly (P less than 0.05) higher in patients than in the control subjects. Of the ICAb-positive patients, 54% were also LyAb-positive, whereas none of the control subjects were doubly positive. IgM-ICAb and IgM-LyAb binding signals were positively correlated. Serum IgM concentrations were significantly (P less than 0.001) greater in patients than in control subjects and were significantly correlated with IgM-LyAb (P less than 0.001) and IgM-ICAb (P less than 0.01). The positivity for IgM binding was not, however, merely a reflection of total IgM, because no such correlation was found in sera from seven patients with Waldenström macroglobulinemia. Clinical onset of type 1 diabetes is apparently accompanied by increased production of IgM. The correlation between IgM concentrations and IgM binding to islet cells might reflect polyclonal activation or natural autoantibodies.