AN EPITOPE IN THE 3RD HYPERVARIABLE REGION OF THE DRB1 GENE IS INVOLVED IN THE SUSCEPTIBILITY TO ENDEMIC PEMPHIGUS FOLIACEUS (FOGO SELVAGEM) IN 3 DIFFERENT BRAZILIAN POPULATIONS

Endemic pemphigus foliaceus or fogo selvagem (FS) in an organ-specific autoimmune skin disease characterized by epidermal vesicles and media ted by autoantibodies. Family cases are frequent and not everyone livi ng in endemic region develops FS suggesting that host factors play a r ole in determining whether exposed individuals will be affected. Becau se our previous works with Brazilian Mestizos and with Xavante Indians have shown that particular HLA alleles confer increased risk for the disease, we decided to extend these studies to another homogeneous pop ulation, the Terena Indians. 19 out of 20 Terena patients were either positive for DRB10404, 1402 or 1406 (p<0.005, RR=14). These findings were in agreement with the data obtained from the Xavante study. In Me stizos the association was with DRB101. All these alleles involved in predisposition to the disease in different populations shared the sam e amino acid sequence at position 67-74 on the third hypervariable reg ion of the DRB1 gene: LLEQRRAA, suggesting that inheritance of this se quence is involved in the susceptibility to FS. When patients and cont rols data from different studies were pooled and analyzed disregarding the ethnic background and the HLA alleles involved, the results obtai ned clearly supported the hypothesis that matching for this epitope is highly significant and predictive of FS predisposition (p<0.00001, RR =6.4).