Association of specific histocompatibility antigens and acanthosis nigricans with insulin resistance.

1. The association or interaction of histocompatibility antigens (HLA) and acanthosis nigricans with type A insulin resistance was studied in 13 patients (10 from family I, 2 from family II and an isolated case) for both sexes. 2. HLA typing for the A, B, C and D antigens was performed by a standard microcytotoxicity test for all patients and for 100 normal controls from the same geographic area. 3. The frequency of HLA B8 was 21% in the control group and 100% in patients with acanthosis nigricans. The frequency of HLA A1B8 was 15% in controls and 73% in acanthotic patients. 4. All the members of family I presenting the association of a possible insulin receptor defect (most likely provided by patient 2) with HLA B8 (provided by patient 1) showed a more pronounced clinical and laboratory expression of insulin resistance. 5. These data suggest that class I antigens of major histocompatibility complex (MHC), A1 and/or B8, may be involved in the pathogenesis of some forms of insulin resistance such as acanthosis nigricans (type A syndrome), possibly by a molecular interaction of the antigens with insulin receptors.