Pathogenesis of systemic sclerosis—current concept and emerging treatments

Masutaka Furue, Chikage Mitoma, Hiroki Mitoma, Gaku Tsuji, Takahito Chiba, Takeshi Nakahara, Uchi Hiroshi, Takafumi Kadono

Research output: Contribution to journalReview article

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)790-797
Number of pages8
JournalImmunologic Research
Volume65
Issue number4
DOIs
Publication statusPublished - Aug 1 2017

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Systemic Scleroderma
Autoantibodies
Endothelial Cells
Fibrosis
Therapeutics
Cytokines
Connective Tissue Growth Factor
Endothelin A Receptors
Angiotensin I
Type I DNA Topoisomerase
Angiotensin Receptors
Myofibroblasts
Interleukin-13
Centromere
Transforming Growth Factors
Autoimmunity
Interleukin-4
Anti-Idiotypic Antibodies
Interleukin-6
B-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Pathogenesis of systemic sclerosis—current concept and emerging treatments. / Furue, Masutaka; Mitoma, Chikage; Mitoma, Hiroki; Tsuji, Gaku; Chiba, Takahito; Nakahara, Takeshi; Hiroshi, Uchi; Kadono, Takafumi.

In: Immunologic Research, Vol. 65, No. 4, 01.08.2017, p. 790-797.

Research output: Contribution to journalReview article

Furue, Masutaka ; Mitoma, Chikage ; Mitoma, Hiroki ; Tsuji, Gaku ; Chiba, Takahito ; Nakahara, Takeshi ; Hiroshi, Uchi ; Kadono, Takafumi. / Pathogenesis of systemic sclerosis—current concept and emerging treatments. In: Immunologic Research. 2017 ; Vol. 65, No. 4. pp. 790-797.
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