Defective Fc-Receptor Functions Associated with the HLA-B8/DRw3 Haplotype: Studies in Patients with Dermatitis Herpetiformis and Normal Subjects

Dermatitis herpetiformis is associated with the HLA-B8/DRw3 haplotype in over 90 per cent of patients, and various percentages have been reported to have circulating immune complexes. Since removal of immune complexes from the circulation is thought to depend on the Fc-receptor function of tissue macro-phages, we studied this function by measuring the clearance of IgG-sensitized autologous erythrocytes in 16 patients with dermatitis herpetiformis, in normal controls with the HLA-B8/DRw3 haplotype, and in randomly selected controls. All patients were HLA-B8 positive, and all of 12 patients tested were HLA-DRw3 positive. Erythrocyte clearance was reduced in eight of the 16 patients, but did not correlate with immune-complex levels. Four of eight controls with HLA-B8/DRw3 also had delayed Fc-receptor-mediated clearance as compared with normal controls. In addition, both patients and HLA-B8/DRw3-positive controls had decreased percentages and total numbers of T cells bearing Fc receptors for IgG. These findings indicate a functional Fc-receptor defect associated with the HLA-B8/DRw3 antigens. (N Engl J Med. 1981; 304:185–92.) THE associations between certain human-leuko-cyte histocompatibility (HLA) antigens and an increased risk of specific diseases has been known for several years. 1 2 3 One such association is that of the HLA-B8 and HLA-DRw3 (HLA-B8/DRw3) antigens with diseases involving immunologic dysfunction. 4 Chronic active hepatitis, celiac disease, myasthenia gravis, sicca syndrome, and systemic lupus erythematosus all occur with increased frequency in persons positive for HLA-B8/DRw3. Another disease thought to be immunologically mediated and strikingly associated with the HLA-B8/DRw3 haplotype is dermatitis herpetiformis, an extremely pruritic papulovesicular skin disorder of unknown origin. Over 90 per cent of patients are HLA-B8/DRw3 positive. 5 The disease is characterized . . .