To the editor,
Takanohashi et al. reported a case of primary membranous nephropathy (pMN) with anti-phospholipase A2 receptor antibody, wherein proteinuria was poorly controlled by glucocorticoids, but complete remission was achieved shortly after acute hepatitis E virus (HEV) infection [1]. This attracts our exceptional interest since acute viral infection resulted in the remission of pMN rather than its recurrence. The authors concluded that an increase in the number of regulatory T cells (Tregs) induced by HEV infection contributed to these conditions. We have the following comments and suggestions.
We are concerned about the possibility that the authors’ suggestions may be insufficient to explain the observed phenomenon. Generally, the proliferation of Tregs occurs subsequently to the activation of innate immunity to inhibit excessive inflammation, which is not an exclusive feature of HEV infection [2]. Infection-induced complete remission of pMN is uncommon; thus, the authors should elucidate why HEV infection resulted in the remission of pMN in this case, whereas other infections have not been documented to affect the activity of pMN, even though these infectious conditions may also cause Tregs’ proliferation.
We propose two potential explanations for the phenomenon in this case. First, HEV infection may be more likely to induce Tregs than others. It depends on the type of infection whether the immunosuppression by Tregs is protective or detrimental to host defense [3]. According to some researchers, the capability to induce Tregs possibly differs from the type of infection [4, 5]. On the basis of these reports and the report regarding HEV infection-induced proliferation of Tregs [6], HEV may be more capable of inducing Tregs than other infectious antigens, leading to protection from autoimmunity as observed in this case. Second, at the onset of HEV infection, proteinuria was in the range of incomplete remission type 2, which was less severe than the initial diagnosis of pMN in this case; thus, remission may have been achieved through Tregs-induced immunosuppression.
In summary, we propose two potential explanations for the unusual occurrence of pMN remission following HEV infection. First, HEV may possess a higher propensity for eliciting Tregs than other infectious antigens, thus affording defense against autoimmunity. Second, remission may have been achieved through Tregs-induced immunosuppression, given that proteinuria at the onset of HEV infection was comparatively mild.
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Conflicts of interest
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Research involving human participants and/or animals
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References
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