Biomarkers in systemic sclerosis: Their potential to predict clinical courses

Journal of Dermatology

Volumn 43, Issue 1, 2016, Pages 29-38

  Hasegawa, Minoru ^a  

^a UNIVERSITY OF FUKUI   (Japan)

Author keywords

autoantibody; biomarker; fibrosis; systemic sclerosis; vascular injury

Indexed keywords

AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; AUTOANTIBODY; BIOLOGICAL MARKER; BRAIN NATRIURETIC PEPTIDE; CCL18 CHEMOKINE; CHEMOKINE; CONNECTIVE TISSUE GROWTH FACTOR; ENDOGLIN; ENDOSTATIN; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; ENDOTHELIN 1; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GLYCOPROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 6; INTERLEUKIN 8; KREBS VON DEN LUNGEN 6 ANTIGEN; MONOCYTE CHEMOTACTIC PROTEIN 1; PADGEM PROTEIN; SURFACTANT PROTEIN D; THROMBOCYTE FACTOR 4; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VASCULOTROPIN; VON WILLEBRAND FACTOR; ANGIOGENIC PROTEIN; ANGIOSTATIC PROTEIN; CELL ADHESION MOLECULE; CYTOKINE; GROWTH PROMOTOR;

ANTIBODY BLOOD LEVEL; CLINICAL FEATURE; DISEASE ACTIVITY; DISEASE CLASSIFICATION; DISEASE COURSE; DISEASE SEVERITY; HUMAN; JAPANESE (PEOPLE); NONHUMAN; PHYSICAL DISABILITY; PREDICTION; PROGNOSIS; PROSPECTIVE STUDY; PROTEIN BLOOD LEVEL; PULMONARY HYPERTENSION; RESPIRATORY FAILURE; REVIEW; SYSTEMIC SCLEROSIS; BLOOD; INTERSTITIAL LUNG DISEASE; SCLERODERMA, SYSTEMIC;

ANGIOGENIC PROTEINS; ANGIOSTATIC PROTEINS; AUTOANTIBODIES; BIOMARKERS; CELL ADHESION MOLECULES; CYTOKINES; GROWTH SUBSTANCES; HUMANS; HYPERTENSION, PULMONARY; LUNG DISEASES, INTERSTITIAL; PROGNOSIS; SCLERODERMA, SYSTEMIC;

EID: 84962381551     PISSN: 03852407     EISSN: 13468138     Source Type: Journal    
DOI: 10.1111/1346-8138.13156     Document Type: Review

References (95)

1. Bhattacharyya S, Wei J, Varga J,. Understanding fibrosis in systemic sclerosis: shifting paradigms, emerging opportunities. Nat Rev Rheumatol 2012 Jan; 8 (1): 42-54.
2. LeRoy EC, Krieg T, Black C, et al,. Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis. J Rheumatol 1988; 15: 202-205.
3. Medsger TA Jr,. Classification, prognosis. In:, Clements PJ, Furst DE, eds. Systemic Sclerosis, 2nd edn. Philadelphia: Lippincott Williams & Wilkins, 2004; 17-28.
4. Steen VD, Medsger TA,. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007 Jul; 66 (7): 940-944.
5. Castro SV, Jimenez SA,. Biomarkers in systemic sclerosis. Biomarkers Med 2010 Feb; 4 (1): 133-147.
6. Hummers LK,. The current state of biomarkers in systemic sclerosis. Curr Rheumatol Rep 2010 Feb; 12 (1): 34-39.
7. Moinzadeh P, Denton CP, Abraham D, et al,. Biomarkers for skin involvement and fibrotic activity in scleroderma. J Eur Acad Dermatol Venereol 2012; 26: 267-276.
8. Castelino FV, Varga J,. Current status of systemic sclerosis biomarkers: applications for diagnosis, management and drug development. Exp Rev Clin Immunol 2013; 9: 1077-1090.
9. Balanescu P, Ladaru A, Balanescu E, Baicus C, Dan GA,. Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review. Biomarkers 2014 Aug; 19 (5): 345-355.
10. Ingegnoli F, Boracchi P, Gualtierotti R, et al,. Improving outcome prediction of systemic sclerosis from isolated Raynaud's phenomenon: role of autoantibodies and nail-fold capillaroscopy. Rheumatology (Oxford) 2010 Apr; 49 (4): 797-805.
11. 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 2008 Dec; 58 (12): 3902-3912.
12. Assassi S, Sharif R, Lasky RE, et al,. Predictors of interstitial lung disease in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort. Arthritis Res Ther 2010; 12 (5): R166.
13. Nikpour M, Hissaria P, Byron J, et al,. Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort. Arthritis Res Ther 2011; 13 (6): R211.
14. Varga J, Abraham D,. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 2007 Mar; 117 (3): 557-567.
15. Lafyatis R,. Transforming growth factor beta-at the centre of systemic sclerosis. Nat Rev Rheumatol 2014 Dec; 10 (12): 706-719.
16. Moustakas A, Heldin CH,. Non-Smad TGF-beta signals. J Cell Sci 2005 Aug 15; 118 (Pt 16): 3573-3584.
17. Whitfield ML, Finlay DR, Murray JI, et al,. Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci USA 2003 Oct 14; 100 (21): 12319-12324.
18. Sargent JL, Milano A, Bhattacharyya S, et al,. A TGFbeta-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity. J Invest Dermatol 2010 Mar; 130 (3): 694-705.
19. Dziadzio M, Smith RE, Abraham DJ, Black CM, Denton CP,. Circulating levels of active transforming growth factor beta1 are reduced in diffuse cutaneous systemic sclerosis and correlate inversely with the modified Rodnan skin score. Rheumatology (Oxford) 2005 Dec; 44 (12): 1518-1524.
20. Denton CP, Merkel PA, Furst DE, et al,. Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum 2007 Jan; 56 (1): 323-333.
21. Rice LM, Padilla CM, McLaughlin SR, et al,. Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients. J Clin Invest 2015 Jul 1; 125 (7): 2795-2807.
22. Krieg T, Takehara K,. Skin disease: a cardinal feature of systemic sclerosis. Rheumatology (Oxford) 2009 Jun; 48 (Suppl 3): iii14-iii18.
23. Sonnylal S, Shi-Wen X, Leoni P, et al,. Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosis. Arthritis Rheum 2010 May; 62 (5): 1523-1532.
24. Takehara K,. Hypothesis: pathogenesis of systemic sclerosis. J Rheumatol 2003 Apr; 30 (4): 755-759.
25. Sato S, Nagaoka T, Hasegawa M, et al,. Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. J Rheumatol 2000 Jan; 27 (1): 149-154.
26. Dziadzio M, Usinger W, Leask A, et al,. N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma. QJM 2005 Jul; 98 (7): 485-492.
27. Khan K, Xu S, Nihtyanova S, et al,. Clinical and pathological significance of interleukin 6 overexpression in systemic sclerosis. Ann Rheum Dis 2012 Jul; 71 (7): 1235-1242.
28. Sato S, Hasegawa M, Takehara K,. Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis. J Dermatol Sci 2001; 27: 140-146.
29. De Lauretis A, Sestini P, Pantelidis P, et al,. Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol 2013 Apr; 40 (4): 435-446.
30. Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ,. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 2000 Mar 23; 404 (6776): 407-411.
31. Gharaee-Kermani M, Denholm EM, Phan SH,. Costimulation of fibroblast collagen and transforming growth factor beta1 gene expression by monocyte chemoattractant protein-1 via specific receptors. J Biol Chem 1996 Jul 26; 271 (30): 17779-17784.
32. Carulli MT, Ong VH, Ponticos M, et al,. Chemokine receptor CCR2 expression by systemic sclerosis fibroblasts: evidence for autocrine regulation of myofibroblast differentiation. Arthritis Rheum 2005 Dec; 52 (12): 3772-3782.
33. Hasegawa M, Sato S, Takehara K,. Augmented production of chemokines (MCP-1, MIP-1α, and MIP-1β) in patients with systemic sclerosis: MCP-1 and MIP-1α may be involved in the development of pulmonary fibrosis. Clin Exp Immunol 1999; 117: 159-165.
34. Antonelli A, Ferri C, Fallahi P, et al,. CXCL10 (alpha) and CCL2 (beta) chemokines in systemic sclerosis-a longitudinal study. Rheumatology (Oxford) 2008 Jan; 47 (1): 45-49.
35. Luzina IG, Atamas SP, Wise R, Wigley FM, Xiao HQ, White B,. Gene expression in bronchoalveolar lavage cells from scleroderma patients. Am J Respir Cell Mol Biol 2002 May; 26 (5): 549-557.
36. Schmidt K, Martinez-Gamboa L, Meier S, et al,. Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients. Arthritis Res Ther 2009; 11 (4): R111.
37. Hasegawa M, Fujimoto M, Matsushita T, Hamaguchi Y, Takehara K, Sato S,. Serum chemokine and cytokine levels as indicators of disease activity in patients with systemic sclerosis. Clin Rheumatol 2011 Feb; 30 (2): 231-237.
38. van Bon L, Affandi AJ, Broen J, et al,. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N Engl J Med 2014; 370: 433-443.
39. Liu X, Mayes MD, Tan FK, et al,. Correlation of interferon-inducible chemokine plasma levels with disease severity in systemic sclerosis. Arthritis Rheum 2013 Jan; 65 (1): 226-235.
40. Abraham D, Lupoli S, McWhirter A, et al,. Expression and function of surface antigens on scleroderma fibroblasts. Arthritis Rheum 1991; 34: 1164-1172.
41. Sfikakis PP, Tesar J, Baraf H, Lipnick R, Klipple G, Tsokos GC,. Circulating intercellular adhesion molecule-1 in patients with systemic sclerosis. Clin Immunol Immunopathol 1993; 68: 88-92.
42. Gruschwitz MS, Hornstein OP, von Den Driesch P,. Correlation of soluble adhesion molecules in the peripheral blood of scleroderma patients with their in situ expression and with disease activity. Arthritis Rheum 1995; 38: 184-189.
43. Ihn H, Sato S, Fujimoto M, et al,. Circulating intercellular adhesion molecule-1 in the sera of patients with systemic sclerosis: enhancement by inflammatory cytokines. Br J Rheumatol 1997; 36: 1270-1275.
44. Stratton RJ, Coghlan JG, Pearson JD, et al,. Different patterns of endothelial cell activation in renal and pulmonary vascular disease in scleroderma. QJM 1998 Aug; 91 (8): 561-566.
45. Mittag M, Beckheinrich P, Haustein UF,. Systemic sclerosis-related Raynaud's phenomenon: effects of iloprost infusion therapy on serum cytokine, growth factor and soluble adhesion molecule levels. Acta Derm Venereol 2001 Aug-Sep; 81 (4): 294-297.
46. Iannone F, Riccardi MT, Guiducci S, et al,. Bosentan regulates the expression of adhesion molecules on circulating T cells and serum soluble adhesion molecules in systemic sclerosis-associated pulmonary arterial hypertension. Ann Rheum Dis 2008 Aug; 67 (8): 1121-1126.
47. Liakouli V, Cipriani P, Marrelli A, Alvaro S, Ruscitti P, Giacomelli R,. Angiogenic cytokines and growth factors in systemic sclerosis. Autoimmun Rev 2011 Aug; 10 (10): 590-594.
48. Hummers LK, Hall A, Wigley FM, Simons M,. Abnormalities in the regulators of angiogenesis in patients with scleroderma. J Rheumatol 2009 Mar; 36 (3): 576-582.
49. Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S,. Soluble adhesion molecules (sVCAM-1, sE-selectin), vascular endothelial growth factor (VEGF) and endothelin-1 in patients with systemic sclerosis: relationship to organ systemic involvement. Clin Rheumatol 2005; 24: 111-116.
50. Distler O, Del Rosso A, Giacomelli R, et al,. Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers. Arthritis Res 2002; 4 (6): R11.
51. Papaioannou AI, Zakynthinos E, Kostikas K, et al,. Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis. BMC Pulm Med 2009; 9: 18.
52. Choi JJ, Min DJ, Cho ML, et al,. Elevated vascular endothelial growth factor in systemic sclerosis. J Rheumatol 2003 Jul; 30 (7): 1529-1533.
53. Viac J, Schmitt D, Claudy A,. Plasma vascular endothelial growth factor levels in scleroderma are not correlated with disease activity. Acta Derm Venereol 2000 Sep-Oct; 80 (5): 383.
54. Distler O, Distler JH, Scheid A, et al,. Uncontrolled expression of vascular endothelial growth factor and its receptors leads to insufficient skin angiogenesis in patients with systemic sclerosis. Circ Res 2004 Jul 9; 95 (1): 109-116.
55. Avouac J, Wipff J, Goldman O, et al,. Angiogenesis in systemic sclerosis: impaired expression of vascular endothelial growth factor receptor 1 in endothelial progenitor-derived cells under hypoxic conditions. Arthritis Rheum 2008 Nov; 58 (11): 3550-3561.
56. Silva I, Almeida J, Vasconcelos C,. A PRISMA-driven systematic review for predictive risk factors of digital ulcers in systemic sclerosis patients. Autoimmun Rev 2015; 14: 140-152.
57. Kahaleh MB, Osborn I, LeRoy EC,. Increased factor VIII/von Willebrand factor antigen and von Willebrand factor activity in scleroderma and in Raynaud's phenomenon. Ann Intern Med 1981 Apr; 94 (4 pt 1): 482-484.
58. Herrick AL, Illingworth K, Blann A, Hay CR, Hollis S, Jayson MI,. Von Willebrand factor, thrombomodulin, thromboxane, beta-thromboglobulin and markers of fibrinolysis in primary Raynaud's phenomenon and systemic sclerosis. Ann Rheum Dis 1996; 55: 122-127.
59. Scheja A, Akesson A, Geborek P, et al,. Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma). Arthritis Res 2001; 3 (3): 178-182.
60. Kumanovics G, Minier T, Radics J, Palinkas L, Berki T, Czirjak L,. Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis. Clin Exp Rheumatol 2008 May-Jun; 26 (3): 414-420.
61. Barnes T, Gliddon A, Dore CJ, Maddison P, Moots RJ, Group QUTS,. Baseline vWF factor predicts the development of elevated pulmonary artery pressure in systemic sclerosis. Rheumatology (Oxford) 2012 Sep; 51 (9): 1606-1609.
62. Mannucci PM, Vanoli M, Forza I, Canciani MT, Scorza R,. Von Willebrand factor cleaving protease (ADAMTS-13) in 123 patients with connective tissue diseases (systemic lupus erythematosus and systemic sclerosis). Haematologica 2003 Aug; 88 (8): 914-918.
63. Wipff J, Avouac J, Borderie D, et al,. Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin. Rheumatology (Oxford) 2008 Jul; 47 (7): 972-975.
64. Fujimoto M, Hasegawa M, Hamaguchi Y, et al,. A clue for telangiectasis in systemic sclerosis: elevated serum soluble endoglin levels in patients with the limited cutaneous form of the disease. Dermatology 2006; 213 (2): 88-92.
65. Shovlin CL, Guttmacher AE, Buscarini E, et al,. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 2000 Mar 6; 91 (1): 66-67.
66. Wipff J, Kahan A, Hachulla E, et al,. Association between an endoglin gene polymorphism and systemic sclerosis-related pulmonary arterial hypertension. Rheumatology (Oxford) 2007 Apr; 46 (4): 622-625.
67. Kohno N, Kyoizumi S, Awaya Y, Fukuhara H, Yamakido M, Akiyama M,. New serum indicator of interstitial pneumonitis activity: sialylated carbohydrate antigen KL-6. Chest 1989; 96: 68-73.
68. Hermans C, Bernard A,. Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med 1999 Feb; 159 (2): 646-678.
69. Kobayashi J, Kitamura S,. KL-6: a serum marker for interstitial pneumonia. Chest 1995; 108: 311-315.
70. Asano Y, Ihn H, Yamane K, et al,. Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. Arthritis Rheum 2001 Jun; 44 (6): 1363-1369.
71. Hant FN, Ludwicka-Bradley A, Wang HJ, et al,. Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J Rheumatol 2009 Apr; 36 (4): 773-780.
72. Yanaba K, Hasegawa M, Takehara K, Sato S,. Comparative study of serum surfactant protein-D and KL-6 concentrations in patients with systemic sclerosis as markers for monitoring the activity of pulmonary fibrosis. J Rheumatol 2004 Jun; 31 (6): 1112-1120.
73. Hieshima K, Imai T, Baba M, et al,. A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes. J Immunol 1997 Aug 1; 159 (3): 1140-1149.
74. Atamas SP, Luzina IG, Choi J, et al,. Pulmonary and activation-regulated chemokine stimulates collagen production in lung fibroblasts. Am J Respir Cell Mol Biol 2003 Dec; 29 (6): 743-749.
75. Kodera M, Hasegawa M, Komura K, Yanaba K, Takehara K, Sato S,. Serum pulmonary and activation-regulated chemokine/CCL18 levels in patients with systemic sclerosis: a sensitive indicator of active pulmonary fibrosis. Arthritis Rheum 2005 Sep; 52 (9): 2889-2896.
76. Tiev KP, Hua-Huy T, Kettaneh A, et al,. Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis. Eur Respir J 2011 Dec; 38 (6): 1355-1360.
77. Schupp J, Becker M, Gunther J, Muller-Quernheim J, Riemekasten G, Prasse A,. Serum CCL18 is predictive for lung disease progression and mortality in systemic sclerosis. Eur Respir J 2014 May; 43 (5): 1530-1532.
78. Prasse A, Pechkovsky DV, Toews GB, et al,. CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis. Arthritis Rheum 2007 May; 56 (5): 1685-1693.
79. Elhaj M, Charles J, Pedroza C, et al,. Can serum surfactant protein D or CC-chemokine ligand 18 predict outcome of interstitial lung disease in patients with early systemic sclerosis? J Rheumatol 2013 Jul; 40 (7): 1114-1120.
80. Steen V, Medsger TA Jr,. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum 2003 Feb; 48 (2): 516-522.
81. Cavagna L, Caporali R, Klersy C, et al,. Comparison of brain natriuretic peptide (BNP) and NT-proBNP in screening for pulmonary arterial hypertension in patients with systemic sclerosis. J Rheumatol 2010 Oct; 37 (10): 2064-2070.
82. Allanore Y, Borderie D, Meune C, et al,. N-terminal pro-brain natriuretic peptide as a diagnostic marker of early pulmonary artery hypertension in patients with systemic sclerosis and effects of calcium-channel blockers. Arthritis Rheum 2003 Dec; 48 (12): 3503-3508.
83. Williams MH, Handler CE, Akram R, et al,. Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. Eur Heart J 2006 Jun; 27 (12): 1485-1494.
84. Allanore Y, Borderie D, Avouac J, et al,. High N-terminal pro-brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis. Arthritis Rheum 2008 Jan; 58 (1): 284-291.
85. Galie N, Hoeper MM, Humbert M, et al,. Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009 Oct; 30 (20): 2493-2537.
86. Braun-Moscovici Y, Nahir AM, Balbir-Gurman A,. Endothelin and pulmonary arterial hypertension. Semin Arthritis Rheum 2004 Aug; 34 (1): 442-453.
87. Abraham DJ, Vancheeswaran R, Dashwood MR, et al,. Increased levels of endothelin-1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease. Am J Pathol 1997 Sep; 151 (3): 831-841.
88. Yamane K, Kashiwagi H, Suzuki N, et al,. Elevated plasma levels of endothelin-1 in systemic sclerosis. Arthritis Rheum 1991 Feb; 34 (2): 243-244.
89. Morelli S, Ferri C, Di Francesco L, et al,. Plasma endothelin-1 levels in patients with systemic sclerosis: influence of pulmonary or systemic arterial hypertension. Ann Rheum Dis 1995 Sep; 54 (9): 730-734.
90. Schmidt J, Launay D, Soudan B, et al,. Assessment of plasma endothelin level measurement in systemic sclerosis. Rev Med Interne 2007 Jun; 28 (6): 371-376.
91. Sulli A, Soldano S, Pizzorni C, et al,. Raynaud's phenomenon and plasma endothelin: correlations with capillaroscopic patterns in systemic sclerosis. J Rheumatol 2009 Jun; 36 (6): 1235-1239.
92. Kim HS, Park MK, Kim HY, Park SH,. Capillary dimension measured by computer-based digitalized image correlated with plasma endothelin-1 levels in patients with systemic sclerosis. Clin Rheumatol 2010; 29: 247-254.
93. Avouac J, Riemekasten G, Meune C, Ruiz B, Kahan A, Allanore Y,. Autoantibodies against Endothelin 1 Type A Receptor Are Strong Predictors of Digital Ulcers in Systemic Sclerosis. J Rheumatol 2015; doi: 10.3899/jrheum.150061.
94. Hasegawa M, Asano Y, Endo H, et al,. Serum chemokine levels as prognostic markers in patients with early systemic sclerosis: a multicenter, prospective, observational study. Mod Rheumatol 2013 Nov; 23 (6): 1076-1084.
95. Hasegawa M, Asano Y, Endo H, et al,. Serum adhesion molecule levels as prognostic markers in patients with early systemic sclerosis: a multicentre, prospective, observational study. PLoS ONE 2014; 9 (2): e88150.