Human leucocyte antigens in idiopathic nephrotic syndrome in children

Abstract

An association of the idiopathic nephrotic syndrome (NS) with certain human leucocyte antigens (HLA) has been reported repeatedly. The aim of this study is to characterize further the clinical and histological features of patients with NS in relation to their HLA phenotypes. HLA antigens were determined in 132 paediatric patients with NS. In 91 steroid-sensitive patients (usually associated with minimal glomerular changes), the antigen frequencies of HLA-DR3, HLA-DR7, and HLA-B8, -DR3 combined were significantly increased compared with controls. The strongest association was observed with the combined occurrence of HLA-B8, -DR3, -DR7 (relative risk 21.5). This association and that with HLA-DR3 alone were strongest in the presence of frequent relapses and steroid dependence compared with children without or with infrequent relapses. The pattern of HLA antigens was similar in the 57 steroid-sensitive patients with biopsy-proven minimal glomerular changes. In 41 children with steroid-resistant NS (usually associated with focal segmental glomerulosclerosis) a similar trend for increased antigen frequencies was found but the data were significant only for the combined occurrence of HLA-B8, -DR3 and -DR7. In all patients combined the frequency of the HLA associations was significantly lower when the age of onset was greater than 8 years compared with that of younger patients. It is concluded that the immunogenetic background of the steroid-sensitive and steroid-resistant NS is different and age-dependent.

Familial Focal Glomerulosclerosis: A Genetic Linkage to the HLA Locus?

“…The steroid-resistant nephrotic syndrome was frequently associated with focal glomerulo sclerosis and the steroid-sensitive nephrotic syndrome with minimal change glomerulonephritis. In steroid-resis tant nephrotic syndrome the frequency of the three HLA alleles, HLA-B8, DR3 and DR7 in combination was sig nificantly increased [7], The steroid-sensitive group was associated with HLA-DR3, DR7 and HLA-B8, DR3 and the highest relative risk was with the combination of HLA-B8, DR3 and DR7. The frequency of HLA associa tion in both groups was reduced when the age of onset was over 8 years [7], Walker et al [1] described 7 patients from 3 families with focal glomerulosclerosis and noted an increase in HLA-A1 (35%) which failed to reach significance when compared to the Caucasian population (30%).…”

“…In steroid-resis tant nephrotic syndrome the frequency of the three HLA alleles, HLA-B8, DR3 and DR7 in combination was sig nificantly increased [7], The steroid-sensitive group was associated with HLA-DR3, DR7 and HLA-B8, DR3 and the highest relative risk was with the combination of HLA-B8, DR3 and DR7. The frequency of HLA associa tion in both groups was reduced when the age of onset was over 8 years [7], Walker et al [1] described 7 patients from 3 families with focal glomerulosclerosis and noted an increase in HLA-A1 (35%) which failed to reach significance when compared to the Caucasian population (30%). The occur rence of the nephrotic syndrome and focal glomeruloscle rosis in HLA-identical Afro-American dizygous twins lends further evidence to a genetic basis for the disease in which both twins share the tissue type HLA-A2, w31, Bw42, Cw2 and DRw3, w5 [2], Two other siblings with different HLA haplotypes were unaffected [2],…”

“…The association was most striking in patients with adult-onset disease [5], In addition the com bination of HLA-DR3 and DR7 has been described in adults with nephrotic syndrome [6]. Ruder et al [7] stud ied 132 children with steroid-sensitive and steroid-resis tant nephrotic syndrome. The steroid-resistant nephrotic syndrome was frequently associated with focal glomerulo sclerosis and the steroid-sensitive nephrotic syndrome with minimal change glomerulonephritis.…”

“…Of the 6 loci studied only the frequency of HLA-DR3 was higher in the Australian dialysis and transplant population with focal glomerulosclerosis than in the Australian Caucasian pop ulation but this did not reach significance, suggesting that non-familial focal glomerulosclerosis is not linked to spe cific HLA loci. When the HLA loci of the 4 sisters with renal disease are compared with the HLA-typing data from other case reports, the presence of HLA-B7, DR3 and DR7 is frequently observed [6,7], In view of the vari ation in disease severity between the sisters sharing the HLA-B7, DR3 and DR7 alleles, it appears that the HLA locus may predispose to the development of focal glomer ulosclerosis but additional factors may be required for disease initiation and progression.…”

“…Several families affected with focal glomerulosclerosis have been reported [1] including 1 case of HLA-identical twins [2], Comparisons of tissue typing data from patients with focal glomerulosclerosis have shown conflicting results [3][4][5][6][7] with linkages mediated through either MHC class-I loci (HLA-A or B), or class-11 loci (HLA-DR). We describe a family of 5 sisters, 3 with biopsy-proven focal glomeru losclerosis and 1 progressing to end-stage renal failure fol lowed by cadaveric renal transplantation.…”