Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report

• Published in: BMC nephrology Vol. 23; no. 1; pp. 1 - 7
• Main Authors: Kohatsu, Kaori, Suzuki, Tomo, Takimoto, Madoka, Matsui, Katsuomi, Hashiguchi, Akinori, Koike, Junki, Shirai, Sayuri
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 16.11.2022; BioMed Central; BMC
• Subjects: Acute kidney injury; Anemia; Antigens; Biopsy; Care and treatment; Case Report; Case reports; CD4 antigen; Creatinine; CTLA-4 haploinsufficiency; CTLA-4 protein; Cytotoxicity; Diagnosis; Drug-induced interstitial nephritis; Effector cells; Fever; Foxp3 protein; Granuloma; Granulomas; Haploinsufficiency; Health aspects; Immunoregulation; Immunosuppressive agents; Inflammation; Kidneys; Laboratories; Levofloxacin; Lymphocytes; Lymphocytes T; Microscopy; Mutation; Nephritis; Nephrology; Patients; Renal function; Steroid hormones; T cells; Thrombocytopenia; Urinalysis; Japan
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-022-02999-x

Abstract Background Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential inhibitory regulator of immune activation. CTLA-4 haploinsufficiency is known to be associated with dysregulation of FOXP3 + regulatory T cells, hyperactivation of effector T cells, and lymphocytic infiltration of multiple organs. However, there have only been a few reports of renal involvement with CTLA-4. Herein, we present a case of acute granulomatous tubulointerstitial nephritis (TIN) in a patient with CTLA-4 haploinsufficiency. Case presentation A 44-year-old man presented with a 3-week history of fever and malaise, and subsequently developed acute kidney injury (AKI) a few days after treatment with levofloxacin (LVFX). A kidney biopsy and immunohistochemical staining revealed granulomatous TIN with dominantly infiltrating CD4 + T cells. General symptoms and renal impairment showed improvement after discontinuation of LVFX and initiation of oral steroids. However, they worsened following steroid tapering. Further, a colon biopsy analysis showed similar findings to the renal tissue analysis. We suspected that granulomatous TIN was possibly associated with CTLA-4 haploinsufficiency. Therefore, the patient was transferred to another hospital for further treatment of CTLA-4 haploinsufficiency using immunosuppressive agents. Conclusions There have been few reports regarding renal involvement of CTLA-4 haploinsufficiency. In the present case, granulomatous TIN could have arisen due to instability of immune regulatory functions, such as CTLA-4 haploinsufficiency, and treatment with LVFX could have triggered immunologic activation and severe inflammation as well as renal dysfunction.