Dilated cardiomyopathy (DCM) is an idiopathic heart muscle disorder. The presence of circulating cardiac antibodies and the association with HLA-DR4 are consistent with autoimmune pathogenesis in a subset of patients. Sixty-eight DCM patients and 277 controls were typed for IgG heavy-chain constant region (Gm) and κ light-chain (Km) allotypes. All patients and 210 of the 277 controls were HLA-DR typed. The Gm (1, 3, 17; 23; 5*, 21, 28) phenotype was overrepresented in DCM compared with controls (25% vs 13%, p = 0.0139, Pc = NS, RR = 2.23). The frequency of this phenotype was higher in patients with younger age at onset, shorter symptom duration, and among those who were positive for cardiac as well as for non-organ-specific autoantibodies than in controls. A higher frequency of the Gm (1,± 2, 3, 17; ± 23; 5*, 21, 28) heterozygous phenotypes was also found in DCM compared to controls (40.91% vs 26389%; p = 0.02, pc = 0.04, RR = 1.88). The finding of Gm heterozygosity in DCM was associated with serum positivity for cardiac antibodies. A higher proportion of DCM patients were positive for both the Gm (1, 3, 17; 23; 5*, 21, 28) phenotype and HLA-DR4 compared to normals (3/68 vs 0/210; p = 0.04, RR = 22.50). A potentiating interactive effect in susceptibility to DCM was also found between the Gm (1, ±2, 3, 17; ±23; 5*, 21, 28) heterozygous phenotypes and HLA-DR4 (7/66 vs 2/207, p = 0.0009, RR = 12.16). These Gm phenotypes may be new markers of susceptibility in DCM, associated with positive autoimmune serology. The potentiating interaction of Gm and HLA-DR4 is in keeping with results reported in other autoimmune diseases.
ASJC Scopus subject areas
- Immunology and Allergy