Increased Concentrations of Total 1gMat Clinical Onset of Type 1 (Insulin-Dependent) Diabetes: Correlation with 1gMBinding to Cells

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 1gM concentrations and for 1gM binding to fixed rat splenocytes (lgM-LyAb) and permeabilized rat islet cells (lgM-ICAb). Comparison of results with those in ageand sex-matched control subjects, by fluorescence-activated cell-sorter analysis, indicated greater concentrations of lgM-LyAb and lgM-ICAb in sera from the patients. 1gM antibodies reacted indiscriminately with islet f3 and islet endocrine non-3 cells. The prevalence of lgM-ICAb, but not of lgM-LyAB, was significantly (P <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. lgM-ICAb and lgM-LyAb binding signals were positively correlated. Serum 1gM concentrations were significantly (P <0.001) greater in patients than in control subjects and were significantly correlated with lgM-LyAb (P <0.001) and lgM-ICAb (P <0.01). The positivity for 1gM binding was not, however, merely a reflectionof total 1gM,because no such correlation was found in sera from seven patients with WaldenstrOm macroglobulinemia. Clinical onset of type 1 diabetes is apparently accompanied by increased production of 1gM. The correlation between 1gMconcentrations and 1gM binding to islet cells might reflect polyclonal activation or natural autoantibodies.