Low disease activity of microscopic polyangiitis in patients with anti-myosin light chain 6 antibody that disrupts actin rearrangement necessary for neutrophil extracellular trap formation

Arthritis Research & Therapy - Tập 24 - Trang 1-9 - 2022
Miku Yoshinari1, Yuka Nishibata1, Sakiko Masuda1, Daigo Nakazawa2, Utano Tomaru3, Yoshihiro Arimura4,5, Koichi Amano6, Yukio Yuzawa7, Ken-Ei Sada8,9, Tatsuya Atsumi2, Hiroaki Dobashi10, Hitoshi Hasegawa11, Masayoshi Harigai12, Seiichi Matsuo13, Hirofumi Makino14, Akihiro Ishizu1
1Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan
2Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
3Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
4Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
5Kichijoji Asahi Hospital, Tokyo, Japan
6Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
7Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
8Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
9Department of Clinical Epidemiology, Kochi Medical School, Kochi University, Nankoku, Japan
10Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan
11Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Ehime, Japan
12Division of Rheumatology, Department of Internal Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan
13Tokai National Higher Education and Research System (THERS), Nagoya, Japan
14Okayama University, Okayama, Japan

Tóm tắt

Neutrophil extracellular traps (NETs) are critically involved in microscopic polyangiitis (MPA) pathogenesis, and some patients with MPA possess anti-NET antibody (ANETA). Anti-myosin light chain 6 (MYL6) antibody is an ANETA that affects NETs. This study aimed to determine the significance of anti-MYL6 antibody in MPA. The influence of anti-MYL6 antibody on NET formation and actin rearrangement necessary for NET formation was assessed by fluorescent staining. An enzyme-linked immunosorbent assay was established to detect serum anti-MYL6 antibody, and the prevalence of this antibody in MPA was determined. Furthermore, the disease activity and response to remission-induction therapy of MPA were compared between anti-MYL6 antibody-positive and anti-MYL6 antibody-negative MPA patients. Anti-MYL6 antibody disrupted G-actin polymerization into F-actin, suppressing phorbol 12-myristate 13-acetate-induced NET formation. Serum anti-MYL6 antibody was detected in 7 of 59 patients with MPA. The Birmingham vasculitis activity score (BVAS) of anti-MYL6 antibody-positive MPA patients was significantly lower than anti-MYL6 antibody-negative MPA patients. Among the nine BVAS evaluation items, the cutaneous, cardiovascular, and nervous system scores of anti-MYL6 antibody-positive MPA patients were significantly lower than anti-MYL6 antibody-negative MPA patients, although other items, including the renal and chest scores, were equivalent between the two groups. The proportion of patients with remission 6 months after initiation of remission-induction therapy in anti-MYL6 antibody-positive MPA patients was significantly higher than in anti-MYL6 antibody-negative MPA patients. Collective findings suggested that anti-MYL6 antibody disrupted actin rearrangement necessary for NET formation and could reduce the disease activity of MPA.

Tài liệu tham khảo

Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1–11. Suppiah R, Robson JC, Grayson PC, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Microscopic Polyangiitis. Arthritis Rheum. 2022;74(3):400–6. Jennette JC, Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol. 2014;10(8):463–73. Nakazawa D, Masuda S, Tomaru U, et al. Pathogenesis and therapeutic interventions for ANCA-associated vasculitis. Nat Rev Rheumatol. 2019;15(2):91–101. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5. Grayson PC, Kaplan MJ. At the Bench: Neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases. J Leukoc Biol. 2016;99(2):253–64. Doring Y, Weber C, Soehnlein O. Footprints of neutrophil extracellular traps as predictors of cardiovascular risk. Arterioscler Thromb Vasc Biol. 2013;33(8):1735–6. Nakazawa D, Tomaru U, Suzuki A, et al. Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2012;64(11):3779–87. Hakkim A, Furnrohr BG, Amann K, et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci U S A. 2010;107(21):9813–8. Nakazawa D, Shida H, Tomaru U, et al. Enhanced formation and disordered regulation of NETs in myeloperoxidase-ANCA-associated microscopic polyangiitis. J Am Soc Nephrol. 2014;25(5):990–7. Shida H, Hashimoto N, Kusunoki Y, et al. Anti-neutrophil extracellular trap antibody in a patient with relapse of anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report. BMC Nephrol. 2018;19(1):145. Hattanda F, Nakazawa D, Watanabe-Kusunoki K, et al. The presence of anti-neutrophil extracellular trap antibody in patients with microscopic polyangiitis. Rheumatology (Oxford). 2019;58(7):1293–8. Zuo Y, Yalavarthi S, Gockman K, et al. Anti-Neutrophil Extracellular Trap Antibodies and Impaired Neutrophil Extracellular Trap Degradation in Antiphospholipid Syndrome. Arthritis Rheum. 2020;72(12):2130–5. Yoshinari M, Hattanda F, Nishibata Y, Masuda S, Nakazawa D, Tomaru U, et al. A Novel Antineutrophil Extracellular Trap Antibody Targeting Myosin Light Chain 6 in Microscopic Polyangiitis. J Rheumatol. 2022;49(11):1286–8. Stojkov D, Amini P, Oberson K, et al. ROS and glutathionylation balance cytoskeletal dynamics in neutrophil extracellular trap formation. J Cell Biol. 2017;216(12):4073–90. Metzler KD, Goosmann C, Lubojemska A, et al. A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis. Cell Rep. 2014;8(3):883–96. Masuda S, Nonokawa M, Futamata E, et al. Formation and Disordered Degradation of Neutrophil Extracellular Traps in Necrotizing Lesions of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis. Am J Pathol. 2019;189(4):839–46. Takito J, Otsuka H, Inoue S, et al. Symmetrical retrograde actin flow in the actin fusion structure is involved in osteoclast fusion. Biol Open. 2017;6(7):1104–14. Sada KE, Harigai M, Amano K, et al. Comparison of severity classification in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study. Mod Rheumatol. 2016;26(5):730–7. Harigai M, Nagasaka K, Amano K, et al. 2017 Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis. Mod Rheumatol. 2019;29(1):20–30. Mukhtyar C, Lee R, Brown D, et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis. 2009;68(12):1827–32. Hellmich B, Flossmann O, Gross WL, et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis. 2007;66(5):605–17. Misra DP, Thomas KN, Gasparyan AY, et al. Mechanisms of thrombosis in ANCA-associated vasculitis. Clin Rheumatol. 2021;40(12):4807–15. Takeuchi H, Kawasaki T, Shigematsu K, et al. Neutrophil extracellular traps in neuropathy with anti-neutrophil cytoplasmic autoantibody-associated microscopic polyangiitis. Clin Rheumatol. 2017;36(4):913–7. Mozzini C, Pagani M. Cardiovascular Diseases: Consider Netosis. Curr Probl Cardiol. 2022;47(10):100929. Kryvalap Y, Jiang ML, Kryvalap N, et al. SerpinB13 antibodies promote beta cell development and resistance to type 1 diabetes. Sci Transl Med. 2021;13(588):eabf1587.
Thông tin
Thông tin xuất bản

Arthritis Research & Therapy

Tập 24

1-9

Thông tin tác giả