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    Role of anti-receptor autoantibodies in pathophysiology of scleroderma.
    Autoimmun Rev 2017 Oct 1;16(10):1029-1035. Epub 2017 Aug 1.
    Rheumatology Division, Department of Medicine, Georgetown University, United States.
    The pathophysiology of SSc-mediated organ damage is complex and not well understood. Hallmarks of the disease include skin thickening, vasculopathy and gastrointestinal dysmotility. Diverse anti-nuclear antibodies can be used as biomarkers for classification and prognosis, but their role in producing tissue pathology/organ dysfunction is not established. In contrast, antibodies against cell surface receptors for platelet derived growth factor, angiotensin II, endothelin A, ICAM-1, and type 3 muscarinic acetyl choline receptors may play a major role in skin thickening, vasoconstriction/pulmonary and renal hypertension, ischemia and gastrointestinal dysmotility, respectively. In addition, antibodies to an inhibitory B-lymphocyte surface molecule, CD 22, may allow increased production of other autoantibodies. Each of these types of antibodies have been reported in some SSc patients, and laboratory studies suggest signaling pathways and mechanisms by which they may contribute to disease activity. However, we are far from a consensus on their importance. Additional epidemiologic, mechanistic and physiologic studies are needed. Confirmation of the roles of anti-receptor antibodies and identification of the signaling pathways by which they alter cellular functions would have major implications for treatment of SSc, both in terms of targeting autoantibodies and the cells that produce them, and in the use of small molecules which inhibit their pernicious effects.

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    Vascular receptor autoantibodies in pulmonary arterial hypertension associated with systemic sclerosis.
    Am J Respir Crit Care Med 2014 Oct;190(7):808-17
    1 Department of Rheumatology and Clinical Immunology.
    Rationale: Systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) portends worse outcome than other forms of PAH. Vasoconstrictive and vascular remodeling actions of endothelin (ET) 1 and angiotensin (Ang) II via endothelin receptor type A (ETAR) and Ang receptor type-1 (AT1R) activation are implicated in PAH pathogenesis.

    Objectives: We hypothesized that stimulating autoantibodies (Abs) targeting and activating AT1R and ETAR may contribute to SSc-PAH pathogenesis, and tested their functional and biomarker relevance. Read More
    Vascular hypothesis revisited: Role of stimulating antibodies against angiotensin and endothelin receptors in the pathogenesis of systemic sclerosis.
    Autoimmun Rev 2016 Jul 10;15(7):690-4. Epub 2016 Mar 10.
    Department of Rheumatology, University of Lübeck, Lübeck, Germany. Electronic address:
    Systemic sclerosis (SSc) is a connective tissue disorder of unknown etiology characterized by the presence of multiple autoantibodies, including those against angiotensin and endothelin receptors. Patients with SSc can develop heterogeneous clinical manifestations including microvascular damage, the dysregulation of innate and adaptive immunity, and generalized fibrosis of multiple organs. Autoantibodies against angiotensin II type I receptor (AT1R) and endothelin-1 type A receptor (ETAR) play important roles in the pathogenesis of SSc. Read More
    Functional autoantibodies in systemic sclerosis pathogenesis.
    Curr Rheumatol Rep 2015 May;17(5):34
    Department of Rheumatology and Clinical Immunology, University Hospital Charité, Luisenstraße 13, 10117, Berlin, Germany,
    Circulating antinuclear autoantibodies contribute to the diagnosis of systemic sclerosis (SSc) and correlate with disease-specific organ manifestations. Recent findings show the induction of interstitial lung disease and obliterative vasculopathy by transfer of IgG from SSc patients in healthy mice indicating a contribution of antibodies to SSc pathogenesis. Several functional or agonistic autoantibodies have been described in SSc, thus putting autoimmunity into a new spotlight. Read More
    Autoantibodies to angiotensin and endothelin receptors in systemic sclerosis induce cellular and systemic events associated with disease pathogenesis.
    Arthritis Res Ther 2014 Jan 28;16(1):R29. Epub 2014 Jan 28.
    Introduction: Vasculopathy, inflammatory fibrosis and functional autoantibodies (Abs) are major manifestations of systemic sclerosis (SSc). Abs directed against the angiotensin II type 1 receptor (AT₁R) and endothelin-1 type A receptor (ETAR) are associated with characteristic disease features including vascular, inflammatory, and fibrotic complications indicating their role in SSc pathogenesis. Therefore, the impact of anti-AT₁R and anti-ETAR Abs on initiation of inflammation and fibrosis was analyzed. Read More