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Crescentic IgA nephropathy after administration of human monoclonal interleukin-12/23p40 antibody in a patient with Crohn’s disease: a case report

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Abstract

Ustekinumab (UST), an interleukin (IL)-12/IL-23-blocking monoclonal antibody, is a novel therapeutic option for Crohn’s disease (CD). We describe a 24-year-old man with CD who showed an abrupt decline in renal function after administration of UST. Twenty-nine months previously, the patient was diagnosed with CD, and abnormal urinalysis findings in health checkup were coincidentally found at that time. Three months previously, treatment for CD was switched from infliximab to UST because of therapy-resistant severe diarrhea and bloody stools. A single dose of UST (260 mg) was initially intravenously administered, followed by single subcutaneous administration (90 mg) 2 months later. Thereafter, the patient exhibited rapid renal dysfunction with significant urinary abnormalities, although his gastrointestinal symptoms had completely disappeared. He was admitted to our hospital for further examination and treatment. Renal pathologic findings were compatible with crescentic glomerulonephritis consisting of almost fibro-cellular crescents. Immunofluorescent study showed IgA and C3 deposition in the glomerular mesangial area and IgA subclass staining revealed predominant IgA1 with concomitant mild IgA2 deposition. Furthermore, galactose-deficient IgA1 (Gd-IgA1) was also positive in the mesangial area. In addition, serum-Gd-IgA1 level was moderately increased. UST treatment was stopped and he responded to intensive steroid therapy with a parallel reduction of serum creatinine and Gd-IgA1 levels without flare of gastrointestinal symptoms. To our knowledge, this is the first case of immunoglobulin A nephropathy (IgAN) in patient with CD that might be aggravated by UST treatment. We presume that inhibition of IL-12/23 signaling with UST may cause to form crescentic IgAN by enhancing Gd-IgA1 production.

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Acknowledgements

We greatly appreciate the excellent technical assistance provided by Ms. Tomoko Suzuki.

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan

    Nobuhiro Kanazawa, Yukihiro Wada, Yasuto Shikida, Motonori Sugiyama, Maki Abe, Masayuki Iyoda & Takanori Shibata

  2. Division of Microscopic Anatomy, Department of Anatomy, Showa University School of Medicine, Tokyo, Japan

    Minako Akiyama & Kazuho Honda

Authors
  1. Nobuhiro Kanazawa
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  2. Yukihiro Wada
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  3. Minako Akiyama
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  4. Yasuto Shikida
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  5. Motonori Sugiyama
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  6. Maki Abe
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  7. Masayuki Iyoda
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  8. Kazuho Honda
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  9. Takanori Shibata
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Corresponding author

Correspondence to Yukihiro Wada.

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Conflict of interest

Y. Wada received Speakers Bureau from Mitsubishi Tanabe Pharma Corporation and T. Shibata has received research funding from Mitsubishi Tanabe Pharma Corporation, although the funder played no role in the present case of the manuscript.

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Informed consent was obtained from the patient described in the present case.

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Kanazawa, N., Wada, Y., Akiyama, M. et al. Crescentic IgA nephropathy after administration of human monoclonal interleukin-12/23p40 antibody in a patient with Crohn’s disease: a case report. CEN Case Rep 9, 204–209 (2020). https://doi.org/10.1007/s13730-020-00457-x

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  • DOI: https://doi.org/10.1007/s13730-020-00457-x

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