INCREASED INCIDENCE OF HLA-B40 GROUP ANTIGENS IN CHILDREN WITH HEMOLYTIC-UREMIC SYNDROME

Hemolytic uremic syndrome (HUS) develops in 25-30% of children infecte d with Escherichia coli strains that produce Shiga-Like toxins, also k nown as verocytotoxins. Mild HUS also occurs in 1 in 4 of the other fa mily members, suggesting a familial predisposition to HUS. To understa nd the possible genetic predisposition, the frequency of HLA antigens was evaluated in 30 children (12 boys, 18 girls; mean age 3.8 years) w ith HUS following a prodrome of bloody diarrhea. When compared to a bl ood donor population from the same geographic area and ethnic backgrou nd, no significant differences were noted in the frequency of HLA-A, H LA-C, HLA-DR, and HLA-DQ antigens. However, the frequency of HLA-B40 a nd its splits (B60, 61, 41, 47) was significantly higher in the study population (corrected p<0.005). The relative risk of developing HUS wa s 6.04 when HLA-B40 and HLA-B40 split products were present, and the r isk increased to 8.5 when the analysis was extended to include the cro ss-reactive antigens B44 and B13. These HLA-B antigens share common am ino acid sequences at positions 41-45 and 67-74 on the alpha-1 domain of the HLA class I molecule. Our data suggest that the inheritance of HLA-B40, its splits, and cross-reactive antigens increases the risk of developing HUS.