Clinicopathological features of tubulointerstitial nephritis (TIN) associated with irAE, COVID-19 infection, and COVID-19 vaccination in comparison with classical allergic TIN

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Abstract Title

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Daisuke

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Fujomoto

Co-author 1

Takashige Kuwabara ktakasea@kumamoto-u.ac.jp Kumamoto University Graduate School of Medical Sciences Nephrology Kumamoto

Co-author 2

Teruhiko Mizumoto tmizumoto@kumamoto-u.ac.jp Kumamoto University Graduate School of Medical Sciences Nephrology Kumamoto

Co-author 3

Yuichiro Izumi izumi_yu@kumamoto-u.ac.jp Kumamoto University Graduate School of Medical Sciences Nephrology Kumamoto

Co-author 4

Masataka Adachi m-adachi@gpo.kumamoto-u.ac.jp Kumamoto University Graduate School of Medical Sciences Nephrology Kumamoto

Co-author 5

Yuko Miyasato kbswy196@yahoo.co.jp Kumamoto University Hospital Diagnostic Pathology Kumamoto

Co-author 6

Yoshiki Mikami mika@kuhp.kyoto-u.ac.jp Kumamoto University Hospital Diagnostic Pathology Kumamoto

Co-author 7

Masashi Mukoyama mmuko@kumamoto-u.ac.jp Kumamoto University Graduate School of Medical Sciences Nephrology Kumamoto

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

In recent decades, there has been a significant increase in the frequency of immune-related adverse event (irAE)–associated renal injury due to the dramatic advances of anti-cancer immunotherapy. Of these, the most popular renal lesion is irAE-associated tubulointerstitial nephritis (irAE-TIN). Since the COVID-19 pandemic, we also often experience cases with COVID-19–associated TIN (COVID-19-TIN) and mRNA vaccine–associated TIN (mRNAvac-TIN). In this report, we describe the similar clinical course and histopathological features of these three types of TIN cases, which may differ from those of classical allergic TIN (CA-TIN).

Methods

Common clinical and pathological features in three cases with irAE-TIN, COVID-19-TIN, and mRNAvac-TIN each are summarized. The interstitial infiltrating cells were evaluated by immunohistochemistry of immune-cell surface markers including CD3, CD20, CD4, CD8 and CD68.

Results

In all three cases, the renal function decline was only partially recovered by treatment with moderate-dose steroid therapy. The mRNAvac-TIN case had a relapse during steroid tapering. Renal biopsy findings commonly indicated severe TIN lesions with tubulitis where CD3+T cells infiltrated more intense than CD20+B cells. Of note, CD8+T cells were markedly more dominant than CD4+T cells in all cases, accompanied by CD68+macrophage infiltration. Representative findings of COVID-19-TIN are indicated in Figure.

Conclusions

Compared to CA-TIN, generally responding well to steroids with a favorable prognosis, irAE-TIN was reported to show relatively partial and slower recovery to treatment. In the present study, COVID-19-TIN and mRNAvac-TIN cases showed a similar clinical course, including only partial improvement and relapse during steroid reduction. Immunostaining revealed significant tubulitis in all cases, with a predominant infiltration of T cells, especially CD8+T cells. These findings differ clearly from CA-TIN in which CD4+T cells are reported as most abundant cells. Renal lesions associated with irAE and mRNA vaccine other than TIN also vary significantly, suggesting the involvement of inappropriate activation of cellular immunity. More detailed investigations are needed to elucidate the pathogenesis of these new classes of TIN.

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