IgA腎症の最新治療とその背景
IgA（immunoglobulin A）腎症は，世界で最も頻度の高い原発糸球体腎炎で，特に日本を含む東アジアで頻度が高い．未治療の場合，約4割が末期腎不全に至る予後不良の疾患であり，国内外を問わず本症に起因し若くして維持透析となる患者は多く，医療経済上も深刻な問題となっている．近年，糖鎖異常IgAと関連免疫複合体が本症の発症・進展のカギを握ることが証明され，その産生抑制と糸球体沈着後の炎症制御を目的とした治療薬の開発が進んでいる．なかでも，粘膜面で感作を受けた成熟IgA産生B細胞を標的とした薬剤や，糖鎖異常IgAの糸球体沈着に伴い活性化される補体古典経路及びレクチン経路を標的とした薬剤の国際...
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| Published in | 日本内科学会雑誌 Vol. 110; no. 10; pp. 2286 - 2292 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本内科学会
10.10.2021
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-5384 1883-2083 |
| DOI | 10.2169/naika.110.2286 |
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| Abstract | IgA（immunoglobulin A）腎症は，世界で最も頻度の高い原発糸球体腎炎で，特に日本を含む東アジアで頻度が高い．未治療の場合，約4割が末期腎不全に至る予後不良の疾患であり，国内外を問わず本症に起因し若くして維持透析となる患者は多く，医療経済上も深刻な問題となっている．近年，糖鎖異常IgAと関連免疫複合体が本症の発症・進展のカギを握ることが証明され，その産生抑制と糸球体沈着後の炎症制御を目的とした治療薬の開発が進んでいる．なかでも，粘膜面で感作を受けた成熟IgA産生B細胞を標的とした薬剤や，糖鎖異常IgAの糸球体沈着に伴い活性化される補体古典経路及びレクチン経路を標的とした薬剤の国際治験が進行中で，その結果が期待されている．こういった複数の有望な根治治療薬の開発が進み，治療選択肢が増えれば病期・病態に応じた治療が可能となり，本症による透析移行の阻止は実現可能と考える．本稿では，これら薬剤に関する病態の背景や，現状を概説する． |
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| AbstractList | IgA（immunoglobulin A）腎症は，世界で最も頻度の高い原発糸球体腎炎で，特に日本を含む東アジアで頻度が高い．未治療の場合，約4割が末期腎不全に至る予後不良の疾患であり，国内外を問わず本症に起因し若くして維持透析となる患者は多く，医療経済上も深刻な問題となっている．近年，糖鎖異常IgAと関連免疫複合体が本症の発症・進展のカギを握ることが証明され，その産生抑制と糸球体沈着後の炎症制御を目的とした治療薬の開発が進んでいる．なかでも，粘膜面で感作を受けた成熟IgA産生B細胞を標的とした薬剤や，糖鎖異常IgAの糸球体沈着に伴い活性化される補体古典経路及びレクチン経路を標的とした薬剤の国際治験が進行中で，その結果が期待されている．こういった複数の有望な根治治療薬の開発が進み，治療選択肢が増えれば病期・病態に応じた治療が可能となり，本症による透析移行の阻止は実現可能と考える．本稿では，これら薬剤に関する病態の背景や，現状を概説する． |
| Author | 鈴木, 仁 鈴木, 祐介 二瓶, 義人 |
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| Copyright | 2021 一般社団法人 日本内科学会 |
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| References | 11) Martin-Penagos L, et al: A proliferation-inducing ligand increase precedes IgA nephropathy recurrence in kidney transplant recipients. Clin Transplant 33: e13502, 2019. 10) Kiryluk K, et al: Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 46: 1187-1196, 2014. 9) Hartono C, et al: Bortezomib for reduction of proteinuria in IgA nephropathy. Kidney Int Rep 3: 861-866, 2018. 5) Fellström BC, et al: Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet 389: 2117-2127, 2017 8) Lafayette RA, et al: A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. J Am Soc Nephrol 28: 1306-1313, 2017. 16) Espinosa M, et al: Mesangial C4d deposition: a new prognostic factor in IgA nephropathy. Nephrol Dial Transplant 24: 886-891, 2009. 13) Makita Y, et al: TLR9 activation induces aberrant IgA glycosylation via APRIL- and IL-6-mediated pathways in IgA nephropathy. Kidney Int 97: 340-349, 2020. 2) Suzuki H, et al: Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 119: 1668-1677, 2009. 6) Hotta O, et al: Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis 38: 736-743, 2001. 3) Suzuki H, et al: IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis. Kidney Int 93: 700-705, 2018. 12) Muto M, et al: Toll-like receptor 9 stimulation induces aberrant expression of a proliferation-inducing ligand by tonsillar germinal center B cells in IgA nephropathy. J Am Soc Nephrol 28: 1227-1238, 2017. 7) Hirano K, et al: Association between tonsillectomy and outcomes in patients with immunoglobulin A nephropathy. JAMA Netw Open 2: e194772, 2019. 14) Myette JR, et al: A proliferation inducing ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy. Kidney Int 96: 104-116, 2019. 17) Guo W, et al: Mannose-binding lectin levels could predict prognosis in IgA nephropathy. J Am Soc Nephrol 28: 3175-3181, 2017. 1) Moldoveanu Z, et al: Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. Kidney Int 71: 1148-1154, 2007. 4) 鈴木祐介: IgA腎症の病因解明と治療の進歩. 日内会誌 109: 1976-1982, 2020. 15) McCarthy DD, et al: Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy. J Clin Invest 121: 3991-4002, 2011. |
| References_xml | – reference: 13) Makita Y, et al: TLR9 activation induces aberrant IgA glycosylation via APRIL- and IL-6-mediated pathways in IgA nephropathy. Kidney Int 97: 340-349, 2020. – reference: 10) Kiryluk K, et al: Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 46: 1187-1196, 2014. – reference: 17) Guo W, et al: Mannose-binding lectin levels could predict prognosis in IgA nephropathy. J Am Soc Nephrol 28: 3175-3181, 2017. – reference: 6) Hotta O, et al: Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis 38: 736-743, 2001. – reference: 5) Fellström BC, et al: Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet 389: 2117-2127, 2017 – reference: 11) Martin-Penagos L, et al: A proliferation-inducing ligand increase precedes IgA nephropathy recurrence in kidney transplant recipients. Clin Transplant 33: e13502, 2019. – reference: 9) Hartono C, et al: Bortezomib for reduction of proteinuria in IgA nephropathy. Kidney Int Rep 3: 861-866, 2018. – reference: 4) 鈴木祐介: IgA腎症の病因解明と治療の進歩. 日内会誌 109: 1976-1982, 2020. – reference: 2) Suzuki H, et al: Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 119: 1668-1677, 2009. – reference: 15) McCarthy DD, et al: Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy. J Clin Invest 121: 3991-4002, 2011. – reference: 3) Suzuki H, et al: IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis. Kidney Int 93: 700-705, 2018. – reference: 1) Moldoveanu Z, et al: Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. Kidney Int 71: 1148-1154, 2007. – reference: 8) Lafayette RA, et al: A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. J Am Soc Nephrol 28: 1306-1313, 2017. – reference: 7) Hirano K, et al: Association between tonsillectomy and outcomes in patients with immunoglobulin A nephropathy. JAMA Netw Open 2: e194772, 2019. – reference: 12) Muto M, et al: Toll-like receptor 9 stimulation induces aberrant expression of a proliferation-inducing ligand by tonsillar germinal center B cells in IgA nephropathy. J Am Soc Nephrol 28: 1227-1238, 2017. – reference: 14) Myette JR, et al: A proliferation inducing ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy. Kidney Int 96: 104-116, 2019. – reference: 16) Espinosa M, et al: Mesangial C4d deposition: a new prognostic factor in IgA nephropathy. Nephrol Dial Transplant 24: 886-891, 2009. |
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| Title | IgA腎症の最新治療とその背景 |
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