Advanced search
Publication Cover
Expert Review of Dermatology Volume 8, 2013 - Issue 3
Journal homepage
10
Views
1
CrossRef citations to date
0
Altmetric
Review

Developments into understanding the pathogenesis of systemic sclerosis

Nicolas Hunzelmann Department of Dermatology, University of Cologne, Kerpener Street 62, 50924 Köln, Germany. [email protected]
Pages 267-276 | Published online: 10 Jan 2014

References

  • Masi AT, Rodnan GP, Medsger TA et al. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum. 23, 581–590 (1980).
  • Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N. Engl. J. Med. 360(19), 1989–2003 (2009).
  • Galluccio F, Walker UA, Nihtyanova S et al. Registries in systemic sclerosis: a worldwide experience. Rheumatology (Oxford) 50(1), 60–68 (2011).
  • Zhou X, Lee JE, Arnett FC et al. HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans. Arthritis Rheum. 60(12), 3807–3814 (2009).
  • Radstake TR, Gorlova O, Rueda B et al.; Spanish Scleroderma Group. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat. Genet. 42(5), 426–429 (2010).
  • Allanore Y, Saad M, Dieudé P et al. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis. PLoS Genet. 7(7), e1002091 (2011).
  • Nashid M, Khanna PP, Furst DE et al.; investigators of the d-penicillamine, human recombinant relaxin and oral bovine type I collagen clinical trials. Gender and ethnicity differences in patients with diffuse systemic sclerosis – analysis from three large randomized clinical trials. Rheumatology (Oxford) 50(2), 335–342 (2011).
  • Arnett FC, Howard RF, Tan F et al. Increased prevalence of systemic sclerosis in a Native American tribe in Oklahoma. Association with an Amerindian HLA haplotype. Arthritis Rheum. 39(8), 1362–1370 (1996).
  • Agarwal SK, Reveille JD. The genetics of scleroderma (systemic sclerosis). Curr. Opin. Rheumatol. 22(2), 133–138 (2010).
  • Crilly A, Hamilton J, Clark CJ, Jardine A, Madhok R. Analysis of transforming growth factor β1 gene polymorphisms in patients with systemic sclerosis. Ann. Rheum. Dis. 61(8), 678–681 (2002).
  • Sato H, Lagan AL, Alexopoulou C et al. The TNF-863 A allele strongly associates with anticentromere antibody positivity in scleroderma. Arthritis Rheum. 50(2), 558–564 (2004).
  • Fonseca C, Renzoni E, Sestini P et al. Endothelin axis polymorphisms in patients with scleroderma. Arthritis Rheum. 54(9), 3034–3042 (2006).
  • Hata R, Akai J, Kimura A, Ishikawa O, Kuwana M, Shinkai H. Association of functional microsatellites in the human type I collagen α2 chain (COL1A2) gene with systemic sclerosis. Biochem. Biophys. Res. Commun. 272(1), 36–40 (2000).
  • Tan FK, Wang N, Kuwana M et al. Association of fibrillin 1 single-nucleotide polymorphism haplotypes with systemic sclerosis in Choctaw and Japanese populations. Arthritis Rheum. 44(4), 893–901 (2001).
  • Zhou X, Tan FK, Reveille JD et al. Association of novel polymorphisms with the expression of SPARC in normal fibroblasts and with susceptibility to scleroderma. Arthritis Rheum. 46(11), 2990–2999 (2002).
  • Manetti M, Allanore Y, Saad M et al. Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis. Ann. Rheum. Dis. 71(6), 1034–1041 (2012).
  • Arnett FC, Gourh P, Shete S et al. Major histocompatibility complex (MHC) class II alleles, haplotypes and epitopes which confer susceptibility or protection in systemic sclerosis: analyses in 1300 caucasian, African–American and Hispanic cases and 1000 controls. Ann. Rheum. Dis. 69(5), 822–827 (2010).
  • Kuwana M, Okano Y, Kaburaki J, Inoko H. HLA class II genes associated with anticentromere antibody in Japanese patients with systemic sclerosis (scleroderma). Ann. Rheum. Dis. 54(12), 983–987 (1995).
  • Dieudé P, Wipff J, Guedj M et al. BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4. Arthritis Rheum. 60(11), 3447–3454 (2009).
  • Rueda B, Gourh P, Broen J et al. BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in caucasians. Ann. Rheum. Dis. 69(4), 700–705 (2010).
  • Gourh P, Agarwal SK, Martin E et al. Association of the C8orf13-BLK region with systemic sclerosis in North-American and European populations. J. Autoimmun. 34(2), 155–162 (2010).
  • Gourh P, Arnett FC, Tan FK et al. Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis. Ann. Rheum. Dis. 69(3), 550–555 (2010).
  • Bossini-Castillo L, Broen JC, Simeon CP et al. A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort. Ann. Rheum. Dis. 70(4), 638–641 (2011).
  • Rueda B, Broen J, Simeon C et al. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Hum. Mol. Genet. 18(11), 2071–2077 (2009).
  • Dieudé P, Guedj M, Wipff J et al. STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis. Arthritis Rheum. 60(8), 2472–2479 (2009).
  • Gorman CL, Russell AI, Zhang Z, Cunninghame Graham D, Cope AP, Vyse TJ. Polymorphisms in the CD3Z gene influence TCRzeta expression in systemic lupus erythematosus patients and healthy controls. J. Immunol. 180(2), 1060–1070 (2008).
  • Bossini-Castillo L, Martin JE, Broen J et al.; Spanish Scleroderma Group. A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in caucasian populations. Hum. Mol. Genet. 21(4), 926–933 (2012).
  • Mattuzzi S, Barbi S, Carletto A et al. Association of polymorphisms in the IL1B and IL2 genes with susceptibility and severity of systemic sclerosis. J. Rheumatol. 34(5), 997–1004 (2007).
  • Cénit MC, Simeón CP, Vonk MC et al.; Spanish Scleroderma Group. Influence of the IL6 gene in susceptibility to systemic sclerosis. J. Rheumatol. 39(12), 2294–2302 (2012).
  • Dieudé P, Bouaziz M, Guedj M et al. Evidence of the contribution of the X chromosome to systemic sclerosis susceptibility: association with the functional IRAK1 196Phe/532Ser haplotype. Arthritis Rheum. 63(12), 3979–3987 (2011).
  • Dieudé P, Guedj M, Wipff J et al. The PTPN22 620 W allele confers susceptibility to systemic sclerosis: findings of a large case–control study of European caucasians and a meta-analysis. Arthritis Rheum. 58(7), 2183–2188 (2008).
  • Momot T, Koch S, Hunzelmann N et al. Association of killer cell immunoglobulin-like receptors with scleroderma. Arthritis Rheum. 50(5), 1561–1565 (2004).
  • Schwinzer R, Witte T, Hundrieser J et al. Enhanced frequency of a PTPRC (CD45) exon A mutation (77C– > G) in systemic sclerosis. Genes Immun. 4(2), 168–169 (2003).
  • Bossini-Castillo L, Martin JE, Broen J et al.; Spanish Scleroderma Group*. Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study. Ann. Rheum. Dis. 72(4), 602–607 (2013).
  • Koumakis E, Giraud M, Dieudé P et al. Brief report: candidate gene study in systemic sclerosis identifies a rare and functional variant of the TNFAIP3 locus as a risk factor for polyautoimmunity. Arthritis Rheum. 64(8), 2746–2752 (2012).
  • Sharif R, Mayes MD, Tan FK et al. IRF5 polymorphism predicts prognosis in patients with systemic sclerosis. Ann. Rheum. Dis. 71(7), 1197–1202 (2012).
  • Martín JE, Bossini-Castillo L, Martín J. Unraveling the genetic component of systemic sclerosis. Hum. Genet. 131(7), 1023–1037 (2012).
  • Tan FK, Zhou X, Mayes MD et al. Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients. Rheumatology (Oxford) 45(6), 694–702 (2006).
  • Duan H, Fleming J, Pritchard DK et al. Combined analysis of monocyte and lymphocyte messenger RNA expression with serum protein profiles in patients with scleroderma. Arthritis Rheum. 58(5), 1465–1474 (2008).
  • Hunzelmann N, Genth E, Krieg T et al.; Registry of the German Network for Systemic Scleroderma. The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford) 47(8), 1185–1192 (2008).
  • Pakozdi A, Nihtyanova S, Moinzadeh P, Ong VH, Black CM, Denton CP. Clinical and serological hallmarks of systemic sclerosis overlap syndromes. J. Rheumatol. 38(11), 2406–2409 (2011).
  • Assassi S, Mayes MD, Arnett FC et al. Systemic sclerosis and lupus: points in an interferon-mediated continuum. Arthritis Rheum. 62(2), 589–598 (2010).
  • Gardner H, Shearstone JR, Bandaru R et al. Gene profiling of scleroderma skin reveals robust signatures of disease that are imperfectly reflected in the transcript profiles of explanted fibroblasts. Arthritis Rheum. 54(6), 1961–1973 (2006).
  • Pendergrass SA, Lemaire R, Francis IP, Mahoney JM, Lafyatis R, Whitfield ML. Intrinsic gene expression subsets of diffuse cutaneous systemic sclerosis are stable in serial skin biopsies. J. Invest. Dermatol. 132(5), 1363–1373 (2012).
  • Steen VD. Autoantibodies in systemic sclerosis. Semin. Arthritis Rheum. 35(1), 35–42 (2005).
  • Koenig M, Joyal F, Fritzler MJ et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud’s phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum. 58(12), 3902–3912 (2008).
  • Mierau R, Moinzadeh P, Riemekasten G et al. Frequency of disease-associated and other nuclear autoantibodies in patients of the German Network for Systemic Scleroderma: correlation with characteristic clinical features. Arthritis Res. Ther. 13(5), R172 (2011).
  • Dragun D, Müller DN, Bräsen JH et al. Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N. Engl. J. Med. 352(6), 558–569 (2005).
  • Cihakova D, Rose NR. Pathogenesis of myocarditis and dilated cardiomyopathy. Adv. Immunol. 99, 95–114 (2008).
  • Baroni SS, Santillo M, Bevilacqua F et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N. Engl. J. Med. 354(25), 2667–2676 (2006).
  • Classen JF, Henrohn D, Rorsman F et al. Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis. Arthritis Rheum. 60(4), 1137–1144 (2009).
  • Loizos N, Lariccia L, Weiner J et al. Lack of detection of agonist activity by antibodies to platelet-derived growth factor receptor α in a subset of normal and systemic sclerosis patient sera. Arthritis Rheum. 60(4), 1145–1151 (2009).
  • Riemekasten G, Philippe A, Näther M et al. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann. Rheum. Dis. 70(3), 530–536 (2011).
  • Avouac J, Meune C, Ruiz B et al. Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis. Ann. Rheum. Dis. 71(3), 394–399 (2012).
  • Asano Y, Stawski L, Hant F et al. Endothelial Fli1 deficiency impairs vascular homeostasis: a role in scleroderma vasculopathy. Am. J. Pathol. 176(4), 1983–1998 (2010).
  • Maurer B, Busch N, Jüngel A et al. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis. Circulation 120(23), 2367–2376 (2009).
  • Manetti M, Guiducci S, Romano E et al. Overexpression of VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, leads to insufficient angiogenesis in patients with systemic sclerosis. Circ. Res. 109(3), e14–e26 (2011).
  • Kuwana M, Okazaki Y. Quantification of circulating endothelial progenitor cells in systemic sclerosis: a direct comparison of protocols. Ann. Rheum. Dis. 71(4), 617–620 (2012).
  • Manetti M, Guiducci S, Matucci-Cerinic M. The origin of the myofibroblast in fibroproliferative vasculopathy: does the endothelial cell steer the pathophysiology of systemic sclerosis? Arthritis Rheum. 63(8), 2164–2167 (2011).
  • Maurer B, Reich N, Juengel A et al. Fra-2 transgenic mice as a novel model of pulmonary hypertension associated with systemic sclerosis. Ann. Rheum. Dis. 71(8), 1382–1387 (2012).
  • Au K, Singh MK, Bodukam V et al. Atherosclerosis in systemic sclerosis: a systematic review and meta-analysis. Arthritis Rheum. 63(7), 2078–2090 (2011).
  • Kasturi KN, Hatakeyama A, Spiera H, Bona CA. Antifibrillarin autoantibodies present in systemic sclerosis and other connective tissue diseases interact with similar epitopes. J. Exp. Med. 181(3), 1027–1036 (1995).
  • Brinckmann J, Hunzelmann N, El-Hallous E et al. Absence of autoantibodies against correctly folded recombinant fibrillin-1 protein in systemic sclerosis patients. Arthritis Res. Ther. 7(6), R1221–R1226 (2005).
  • Bühling F, Röcken C, Brasch F et al. Pivotal role of cathepsin K in lung fibrosis. Am. J. Pathol. 164(6), 2203–2216 (2004).
  • Königshoff M, Balsara N, Pfaff EM et al. Functional Wnt signaling is increased in idiopathic pulmonary fibrosis. PLoS One 3(5), e2142 (2008).
  • Moinzadeh P, Krieg T, Hellmich M et al. Elevated MMP-7 levels in patients with systemic sclerosis: correlation with pulmonary involvement. Exp. Dermatol. 20(9), 770–773 (2011).
  • Yamashita CM, Dolgonos L, Zemans RL et al. Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis. Am. J. Pathol. 179(4), 1733–1745 (2011).
  • Manetti M, Guiducci S, Romano E et al. Increased serum levels and tissue expression of matrix metalloproteinase-12 in patients with systemic sclerosis: correlation with severity of skin and pulmonary fibrosis and vascular damage. Ann. Rheum. Dis. 71(6), 1064–1072 (2012).
  • Bayle J, Fitch J, Jacobsen K, Kumar R, Lafyatis R, Lemaire R. Increased expression of Wnt2 and SFRP4 in Tsk mouse skin: role of Wnt signaling in altered dermal fibrillin deposition and systemic sclerosis. J. Invest. Dermatol. 128(4), 871–881 (2008).
  • Brinckmann J, Hunzelmann N, Kahle B et al. Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: potential alteration of cell attachment and storage of TGF-β. Lab. Invest. 90(5), 739–752 (2010).
  • Königshoff M, Kramer M, Balsara N et al. WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis. J. Clin. Invest. 119(4), 772–787 (2009).
  • Wei J, Melichian D, Komura K et al. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: a novel mouse model for scleroderma? Arthritis Rheum. 63(6), 1707–1717 (2011).
  • Horn A, Palumbo K, Cordazzo C et al. Hedgehog signaling controls fibroblast activation and tissue fibrosis in systemic sclerosis. Arthritis Rheum. 64(8), 2724–2733 (2012).
  • Dees C, Zerr P, Tomcik M et al. Inhibition of Notch signaling prevents experimental fibrosis and induces regression of established fibrosis. Arthritis Rheum. 63(5), 1396–1404 (2011).
  • Milano A, Pendergrass SA, Sargent JL et al. Molecular subsets in the gene expression signatures of scleroderma skin. PLoS One 3(7), e2696 (2008).
  • Hesselstrand R, Kassner A, Heinegård D, Saxne T. COMP: a candidate molecule in the pathogenesis of systemic sclerosis with a potential as a disease marker. Ann. Rheum. Dis. 67(9), 1242–1248 (2008).
  • Farina G, Lemaire R, Korn JH, Widom RL. Cartilage oligomeric matrix protein is overexpressed by scleroderma dermal fibroblasts. Matrix Biol. 25(4), 213–222 (2006).
  • Steen VD, Medsger TA Jr. Case–control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum. 41(9), 1613–1619 (1998).
  • Whitfield ML, Finlay DR, Murray JI et al. Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc. Natl Acad. Sci. USA 100(21), 12319–12324 (2003).
  • Hsu E, Shi H, Jordan RM, Lyons-Weiler J, Pilewski JM, Feghali-Bostwick CA. Lung tissues in patients with systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension. Arthritis Rheum. 63(3), 783–794 (2011).
  • Pendergrass SA, Hayes E, Farina G et al. Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury. PLoS One 5(8), e12106 (2010).
  • Henes JC, Schmalzing M, Vogel W et al. Optimization of autologous stem cell transplantation for systemic sclerosis – a single-center longterm experience in 26 patients with severe organ manifestations. J. Rheumatol. 39(2), 269–275 (2012).
  • Friedman SL. Evolving challenges in hepatic fibrosis. Nat. Rev. Gastroenterol. Hepatol. 7(8), 425–436 (2010).
  • ten Freyhaus H, Dumitrescu D, Berghausen E, Vantler M, Caglayan E, Rosenkranz S. Imatinib mesylate for the treatment of pulmonary arterial hypertension. Expert Opin. Investig. Drugs 21(1), 119–134 (2012).
  • Montani D, Bergot E, Günther S et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation 125(17), 2128–2137 (2012).
  • Distler JH, Jüngel A, Huber LC et al. Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis. Arthritis Rheum. 56, 9–12 (2007).
  • Pope J, McBain D, Petrlich L et al. Imatinib in active diffuse cutaneous systemic sclerosis: results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center. Arthritis Rheum. 63(11), 3547–3551 (2011).
  • Khanna D, Saggar R, Mayes MD et al. A one-year, Phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosis-associated active interstitial lung disease. Arthritis Rheum. 63(11), 3540–3546 (2011).
  • Richeldi L, Costabel U, Selman M et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N. Engl. J. Med. 365(12), 1079–1087 (2011).
  • Dai R, Ahmed SA. MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl. Res. 157(4), 163–179 (2011).
  • Tomkanova T, Petrek M, Gallo J et al. MicroRNAs: emerging regulators of immune-mediated diseases. Scand. J. Immunol. 75, 129–141 (2011).
  • Maurer B, Stanczyk J, Jüngel A et al. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum. 62(6), 1733–1743 (2010).

Website

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.