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Pathogenesis of systemic sclerosis—current concept and emerging treatments

Immunologic Research volume 65, pages 790–797 (2017)Cite this article

Abstract

Systemic sclerosis (SSc) is an intractable multifaceted disease with high mortality. Although its pathogenesis is not fully understood, recent studies have advanced our knowledge on SSc. The cardinal pathological features of SSc are autoimmunity, vasculopathy, and fibrosis. The B cells in SSc are constitutively activated and lead to the production of a plethora of autoantibodies, such as anti-topoisomerase I and anti-centromere antibodies. In addition to these autoantibodies, which are valuable for diagnostic criteria or biomarkers, many other autoantibodies targeting endothelial cells, including endothelin type A receptor and angiotensin II type I receptor, are known to be functional and induce activation or apoptosis of endothelial cells. The autoantibody-mediated endothelial cell perturbation facilitates inflammatory cell infiltration, cytokine production, and myofibroblastic transformation of fibroblasts and endothelial cells. Profibrotic cytokines, such as transforming growth factor β, connective tissue growth factor, interleukin 4/interleukin 13, and interleukin 6, play a pivotal role in collagen production from myofibroblasts. Specific treatments targeting these causative molecules may improve the clinical outcomes of patients with SSc. In this review, we summarize recent topics on the pathogenesis (autoantibodies, vasculopathy, and fibrosis), animal models, and emerging treatments for SSc.

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Authors and Affiliations

  1. Department of Dermatology, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka, 812-8582, Japan

    Masutaka Furue, Chikage Mitoma, Gaku Tsuji, Takahito Chiba, Takeshi Nakahara & Hiroshi Uchi

  2. Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan

    Masutaka Furue, Chikage Mitoma & Gaku Tsuji

  3. Division of Skin Surface Sensing, Department of Dermatology, Kyushu University, Fukuoka, Japan

    Masutaka Furue & Takeshi Nakahara

  4. Department of Clinical Immunology and Rheumatology/Infectious Disease, Kyushu University, Fukuoka, Japan

    Hiroki Mitoma

  5. Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Japan

    Takafumi Kadono

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  1. Masutaka Furue
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  2. Chikage Mitoma
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  3. Hiroki Mitoma
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  7. Hiroshi Uchi
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Correspondence to Masutaka Furue.

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Furue, M., Mitoma, C., Mitoma, H. et al. Pathogenesis of systemic sclerosis—current concept and emerging treatments. Immunol Res 65, 790–797 (2017). https://doi.org/10.1007/s12026-017-8926-y

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