Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report
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...
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Nephrology |
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| Online Access: | https://doi.org/10.1186/s12882-022-02999-x |
| _version_ | 1811217676329025536 |
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| author | Kaori Kohatsu Tomo Suzuki Madoka Takimoto Katsuomi Matsui Akinori Hashiguchi Junki Koike Sayuri Shirai |
| author_facet | Kaori Kohatsu Tomo Suzuki Madoka Takimoto Katsuomi Matsui Akinori Hashiguchi Junki Koike Sayuri Shirai |
| author_sort | Kaori Kohatsu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T06:58:47Z |
| format | Article |
| id | doaj.art-0154ee6caf6f4844aee90d019fa09f77 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-04-12T06:58:47Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-0154ee6caf6f4844aee90d019fa09f772022-12-22T03:43:03ZengBMCBMC Nephrology1471-23692022-11-012311710.1186/s12882-022-02999-xGranulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case reportKaori Kohatsu0Tomo Suzuki1Madoka Takimoto2Katsuomi Matsui3Akinori Hashiguchi4Junki Koike5Sayuri Shirai6Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of MedicineDepartment of Nephrology, Kameda Medical CenterDepartment of Hematology, St. Marianna University School of Medicine Yokohama City Seibu HospitalDepartment of Nephrology and Hypertension, St. Marianna University School of Medicine Yokohama City Seibu HospitalDepartment of Pathology, Keio University School of MedicineDepartment of Diagnostic Pathology, St. Marianna University School of MedicineDivision of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of MedicineAbstract 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.https://doi.org/10.1186/s12882-022-02999-xCTLA-4 haploinsufficiencyDrug-induced interstitial nephritisGranulomaAcute kidney injuryCase report |
| spellingShingle | Kaori Kohatsu Tomo Suzuki Madoka Takimoto Katsuomi Matsui Akinori Hashiguchi Junki Koike Sayuri Shirai Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report BMC Nephrology CTLA-4 haploinsufficiency Drug-induced interstitial nephritis Granuloma Acute kidney injury Case report |
| title | Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report |
| title_full | Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report |
| title_fullStr | Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report |
| title_full_unstemmed | Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report |
| title_short | Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report |
| title_sort | granulomatous interstitial nephritis with ctla 4 haploinsufficiency a case report |
| topic | CTLA-4 haploinsufficiency Drug-induced interstitial nephritis Granuloma Acute kidney injury Case report |
| url | https://doi.org/10.1186/s12882-022-02999-x |
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