Sheth K J, Gill J C, Leichter H E, Havens P L, Hunter J B
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Nephron. 1994;68(4):433-6. doi: 10.1159/000188303.
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.
溶血性尿毒症综合征（HUS）在25% - 30%感染产生志贺样毒素（也称为维罗毒素）的大肠杆菌菌株的儿童中发生。轻度HUS也在其他家庭成员中每4人中有1人出现，提示HUS存在家族易感性。为了解可能的遗传易感性，对30名（12名男孩，18名女孩；平均年龄3.8岁）在出现血性腹泻前驱症状后发生HUS的儿童进行了HLA抗原频率评估。与来自相同地理区域和种族背景的献血人群相比，HLA - A、HLA - C、HLA - DR和HLA - DQ抗原频率未发现显著差异。然而，研究人群中HLA - B40及其裂解产物（B60、61、41、47）的频率显著更高（校正p < 0.005）。当存在HLA - B40和HLA - B40裂解产物时，发生HUS的相对风险为6.04，当分析扩展至包括交叉反应抗原B44和B13时，风险增加至8.5。这些HLA - B抗原在HLA I类分子α - 1结构域的41 - 45位和67 - 74位共享共同氨基酸序列。我们的数据表明，HLA - B40及其裂解产物和交叉反应抗原的遗传增加了发生HUS的风险。
