Loss of Ia-positive epidermal Langerhans cells at the onset of Type 1 (insulin-dependent) diabetes mellitus

Immunocompetent antigen-presenting Langerhans cells were investigated in skin biopsies of 20 short-term Type 1 (insulin-dependent) diabetic patients and compared with 17 matched normal control subjects. Langerhans cells in epidermal sheet preparations were visualized with a monoclonal anti-HLA DR antibody using indirect immunofluorescence. A significant decrease of Langerhans cells/mm² body surface area was found in 10 patients immediately at the onset of diabetes compared to 10 patients with 6 months duration of diabetes and to normal control subjects (401±30 vs 559±43 vs 611±33, p<0.01 and p<0.002). There was no significant difference in the number of Langerhans cells between patients with 6 months duration of diabetes and control subjects. Examination of the most likely precursor of Langerhans cells, the blood monocytes, indicated an increase of monocyte counts in Type 1 diabetic patients after 6 months duration (344±37 cells/μl vs 191±31 in control subjects, p<0.05) and an inverse correlation between the number of Langerhans cells in skin with the number of monocytes in peripheral blood (at onset: r=-0.73, p<0.01, after 6 months of diabetes: r=-0.61, p<0.05). In addition, a positive correlation between Langerhans cells and daily insulin dose was noted in patients after 6 months of diabetes (r=0.76, p<0.01). The data suggest a loss of Langerhans cells in skin at the onset of Type 1 diabetes and that functional alterations of these and perhaps also other antigenpresenting cells may be involved in the pathogenesis of Type 1 diabetes.