The strong association of HLA-DR4 with spherical mesangial dense deposits in IgA nephropathy
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This study found a link between HLA-DR4 and spherical mesangial dense deposits in Japanese patients with IgA nephropathy. This suggests IgA nephropathy may have distinct subtypes based on genetic and microscopic findings.
Area of Science:
- Immunogenetics
- Nephrology
- Pathology
Background:
- Immunoglobulin A nephropathy (IgA GN) is a common primary glomerulonephritis.
- The role of human leukocyte antigen (HLA) genes in IgA GN pathogenesis is not fully understood.
- Distinct pathological features within IgA GN may have different genetic associations.
Purpose of the Study:
- To investigate the association between specific HLA antigens and pathological findings in Japanese patients with primary IgA nephropathy.
- To determine if the presence of spherical mesangial dense deposits (SMDD) is linked to particular HLA types.
- To explore potential genetic subdivisions of IgA GN based on HLA and electron microscopy.
Main Methods:
- Human leukocyte antigen (HLA) typing (HLA-A, -B, -C, and -DR) was performed on 41 Japanese patients with IgA GN.
- Patients were categorized based on the presence or absence of spherical mesangial dense deposits (SMDD) observed via electron microscopy.
- Frequencies of HLA antigens were compared between IgA GN patients and 63 healthy controls, and within patient subgroups.
Main Results:
- A slight, non-significant increase in HLA-DR4 frequency was observed in the total IgA GN cohort compared to controls.
- A statistically significant increase in HLA-DR4 incidence was found in the subgroup of 24 IgA GN patients exhibiting SMDD (chi^2 = 11.52, RR = 6.45, p < 0.03).
- No specific HLA antigen association was identified in the 17 IgA GN patients without SMDD.
Conclusions:
- The findings suggest a significant association between HLA-DR4 and the presence of SMDD in IgA nephropathy.
- This association indicates that IgA nephropathy might be genetically heterogeneous and potentially classifiable into subtypes.
- Further research into HLA associations with specific electron microscopic findings could refine IgA GN classification and understanding of its pathogenesis.
Abstract:
41 Japanese patients with primary IgA nephropathy (IgA GN) were determined for HLA-A, -B, -C and -DR antigens. The frequency of HLA-DR4 increased slightly in total patients compared with 63 normal control persons, but this increase was not statistically significant. However, 24 patients with spherical mesangial dense deposits (SMDD) in electron micrograph out of 41 patients with IgA GN were found to have markedly increased incidence of HLA-DR4 (chi 2 = 11.52, Relative risk = 6.45, Corrected p less than 0.03). In contrast to this finding, 17 patients without SMDD had no association with any particular HLA antigens. These results suggest that IgA GN might be subdivided by the association of HLA and electron microscopic findings into at least 2 types.