title: Increased incidence of HLA-B40 group antigens in children with hemolytic-uremic syndrome.
abstract: Hemolytic uremic syndrome (HUS) develops in 25-30% of children infected with Escherichia coli strains that produce Shiga-like toxins, also known as verocytotoxins. Mild HUS also occurs in 1 in 4 of the other family members, suggesting a familial predisposition to HUS. To understand the possible genetic predisposition, the frequency of HLA antigens was evaluated in 30 children (12 boys, 18 girls; mean age 3.8 years) with HUS following a prodrome of bloody diarrhea. When compared to a blood donor population from the same geographic area and ethnic background, no significant differences were noted in the frequency of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. However, the frequency of HLA-B40 and its splits (B60, 61, 41, 47) was significantly higher in the study population (corrected p < 0.005). The relative risk of developing HUS was 6.04 when HLA-B40 and HLA-B40 split products were present, and the risk increased to 8.5 when the analysis was extended to include the cross-reactive antigens B44 and B13. These HLA-B antigens share common amino 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.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
authors.forename: K J
authors.initials: KJ
authors.lastname: Sheth
authors.forename: J C
authors.initials: JC
authors.lastname: Gill
authors.forename: H E
authors.initials: HE
authors.lastname: Leichter
authors.forename: P L
authors.initials: PL
authors.lastname: Havens
authors.forename: J B
authors.initials: JB
authors.lastname: Hunter
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000097:blood / Q000150:complications; D005260:Female; D006680:HLA Antigens / Q000097:blood; D015235:HLA-B Antigens / Q000097:blood*; D059947:HLA-B40 Antigen; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000150:complications / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D012016:Reference Values
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; D059947:HLA-B40 Antigen