We reported a significant positive association of each of human leukocyte antigen (HLA)-DR7 and HLA-B35 with fibrillary glomerulonephritis (FGN) in a cohort of 26 patients with FGN.1 We are pleased that El Ters et al.2 have observed a similar association between HLA-DR7 and FGN in their cohort of 16 patients with native kidney failure due to FGN or donor-derived FGN. Together, these findings support a genetic component to this rare glomerulonephritis.
Unlike our study, HLA-B35 was not significantly associated with FGN in the Mayo Clinic cohort,2 raising uncertainty about the significance of HLA-B35 association with FGN. HLA antigens have associations with race and infectious and autoimmune diseases, that may confound analyses of small cohorts. HLA-B35 is one of the largest allelic Class I molecules.3 HLA-B35 appears to increase susceptibility to chronic hepatitis C virus infection in particular populations,4 and hepatitis C infection is significantly associated with Black patients in the setting of FGN.S1,S2 In small cohorts, differences in ethnicity and concurrent diseases may affect the ability to confirm genetic associations.
Larger, ethnicity-matched cohorts are needed to confirm the associations that have been described between HLAs and FGN. Importantly, future investigations may benefit from molecular typing for both HLA Class I and Class I, and from applying genome-wide association studies to more specifically decipher genetic susceptibility loci in patients with FGN beyond serologic typing of HLA antigens.
Footnotes
Supplementary References.
Supplementary Material
References
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