Association of Alport's syndrome with HDL-DR2 antigen in a group of unrelated patients

A few studies have evaluated HLA antigens in Alport's syndrome; however, there are no large population studies. In the present report, we studied 40 unrelated white patients with Alport's syndrome seen at the Unit of Renal Transplantation, Faculty of Medicine of Ribeirao Preto, Sao Paulo, Brazil. HLA-A, -B, -DR and -DQ antigens were typed using a complement-dependent microlymphocytotoxicity assay. A control white populations (N=403) from the same geographical area was also typed for HLA antigens. Although the frequencies of HLA-A and -B antigens of patients were not statistically different from controls, the frequency of HLA-DR2 antigen observed in patients (65 percent) was significantly increased in relation to controls (26 percent; P<0.001). The relative risk and etiologic fraction for HLA-DR2 antigen were 5.2 and 0.525, respectively. Although few immunological abnormalities have been shown in Alport's syndrome, in this report we emphasize the association of HLA molecules and Alport's syndrome. Besides the well-known inherited molecular defects encoded by tyope IV collagen genes in Alport's syndrome, the major histocompatibility alleles may be in linkage disequilibrium with these defective collagen genes.

Basement membrane antibodies in Alport's syndrome.

By the indirect immunofluorescent technique, sera from patients with Alport's syndrome showed a reaction with the basement membrane of the capillary wall of glomeruli and peritubular vessels and nearby interstitial tissue of normal monkey and mouse kidney as a substrate. It also revealed bright staining to the matrix surrounding the clusters of EHS tumor cells and stromal tissues. These reactions were caused by autoantibodies present in these sera. These findings were supported by the detection of antilaminin, nidogen and anti collagen type VI in the sera by ELISA method. These evidences suggest that the Alport's patients developed stage of autoimmunity. The exact causes were not so clear, but seemed to be due to multiple factors.