Tocilizumab-induced immunocomplex glomerulonephritis: a report of two cases
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CASE REPORT
Tocilizumab‑induced immunocomplex glomerulonephritis: a report of two cases Daichi Fukaya1 · Tsutomu Inoue1 · Yuta Kogure2 · Hiroshi Kajiyama3 · Keisuke Ishizawa4 · Takeru Seto1 · Hajime Hasegawa2 · Toshihide Mimura3 · Hirokazu Okada1 Received: 22 October 2019 / Accepted: 15 April 2020 © Japanese Society of Nephrology 2020
Abstract We report here two cases of membranoproliferative glomerulonephritis that developed during treatment of rheumatoid arthritis with tocilizumab. In both cases, the initial findings were proteinuria and haematuria, followed by development of bilateral lower leg oedema. One of the patients was weakly positive for anti-nuclear antibody; both had hypocomplementaemia. The patients’ renal impairment gradually resolved with discontinuation of tocilizumab followed by treatment with moderate doses of oral prednisolone. Pathological examination of renal biopsies resulted in diagnoses of immunocomplex glomerulonephritis and immunofluorescence staining revealed depositions of IgG, IgA, and IgM, accompanied by C3. Tocilizumab rarely induces autoimmune disorders; therefore, the underlying mechanism is unknown. One patient with immunocomplex glomerulonephritis that may have been associated with tocilizumab therapy for rheumatoid arthritis has been reported previously; that patient and our two are similar in their clinical courses and pathological findings. We conclude that such glomerulonephritis can occur during tocilizumab treatment, but this is rare. Clinicians should be aware of the possibility of paradoxical development of autoimmune diseases during tocilizumab therapy. Keywords Tocilizumab · Glomerulonephritis · Rheumatoid arthritis
Introduction Tocilizumab is a humanized monoclonal anti-interleukin (IL)-6 receptor antibody that acts as an IL-6 antagonist. It is used worldwide to treat adults with moderate-to-severe active rheumatoid arthritis (RA) [1]. Because IL-6 is a pleiotropic pro-inflammatory cytokine that is involved in diverse physiological processes, tocilizumab is also used to treat * Hirokazu Okada hirookda@saitama‑med.ac.jp 1
Department of Nephrology, Saitama Medical University, 38 Morohongo, Moroyama‑machi, Iruma‑gun, Saitama 350‑0495, Japan
2
Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
3
Department of Rheumatology and Applied Immunology, Saitama Medical University, Iruma‑gun, Saitama, Japan
4
Division of Diagnostic Pathology and Department of Pathology, Saitama Medical University, Iruma‑gun, Saitama, Japan
Castleman disease [2, 3], other cytokine release syndromes, for example TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) syndrome [4], and the glomerulonephritis that can accompany these diseases [5–9]. Although tocilizumab is generally well tolerated, adverse reactions, including upper respiratory tract infection and hypercholesterolaemia, have been reported [1]. The rate of development of anti-drug antibodies is low [10]; this phenomenon may r
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