Oligotyping for HLA-DQA, -DQB, and -DPB in idiopathic nephrotic syndrome

Abstract.

Associations of human leukocyte antigens (HLA) with the idiopathic nephrotic syndrome (NS) have mainly been described for alleles of the HLA-DR locus. In the present study the polymorphism of HLA-DQ and -DP at the molecular level was investigated in 167 children with NS (129 steroid-sensitive) using the polymerase chain reaction and sequence-specific oligonucleotides in a French and a German cohort. HLA-DR typing was also performed by classical serology. In steroid-sensitive patients we observed an increased frequency of the alleles HLA-DQA1^*0201 and -DQB1^*0201 in both populations with relative risks ranging from 3.8 to 8.5 (P _b <0.01 to P _b <0.00001 after Bonferoni’s correction). In contrast, the frequency of HLA-DQA1^*0102 and DQB1^*0602 was significantly decreased. In children with frequent relapses the HLA associations were generally more pronounced than in those with infrequent or no relapses. Applying logistic regression analysis, a nephrotic child bearing DQA1^*0201 or DR7 was five times more likely to be in the steroid-sensitive group of patients than in the steroid-resistant group compared with nephrotic children not bearing one of these alleles. These HLA alleles therefore seem to be useful indicators of a steroid-sensitive frequently relapsing course of NS. No associations with DPB alleles were observed, which narrows the region genetically involved in the disease susceptibility to the DR-DQ region. Steroid-resistant NS was not associated with HLA.