Biomarkers in systemic sclerosis

Biomarkers in Medicine

Volumn 4, Issue 1, 2010, Pages 133-147

  Castro, Susan V ^a   Jimenez, Sergio A ^a  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

Biomarker; Endothelial cells; Fibrosis; Pulmonary artery hypertension; Pulmonary fibrosis; Scleroderma; Systemic sclerosis; TGF b

Indexed keywords

AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; AUTOANTIBODY; BIOLOGICAL MARKER; CENTROMERE ANTIBODY; CHEMOKINE; COLLAGEN TYPE 1; COLLAGEN TYPE 3; DNA DIRECTED RNA POLYMERASE ANTIBODY; DNA DIRECTED RNA POLYMERASE III ANTIBODY; ENDOTHELIN 1; FIBRILLARIN ANTIBODY; KREBS VON DEN LUNGEN 6 ANTIGEN; SCL 70 ANTIBODY; SURFACTANT PROTEIN A; SURFACTANT PROTEIN D; UNCLASSIFIED DRUG;

CELLULAR IMMUNITY; DISEASE CLASSIFICATION; DISEASE COURSE; DISEASE MARKER; ENDOTHELIUM CELL; FIBROSIS; GENE EXPRESSION; HUMORAL IMMUNITY; LUNG FIBROSIS; MICROARRAY ANALYSIS; PATHOGENESIS; PULMONARY HYPERTENSION; REVIEW; SYSTEMIC SCLEROSIS; TREATMENT RESPONSE; VALIDATION STUDY;

AUTOANTIBODIES; BIOLOGICAL MARKERS; CYTOKINES; ENDOTHELIAL CELLS; HUMANS; HYPERTENSION, PULMONARY; IMMUNITY, CELLULAR; MODELS, BIOLOGICAL; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROTEOMICS; PULMONARY FIBROSIS; SCLERODERMA, SYSTEMIC;

EID: 77951685582     PISSN: 17520363     EISSN: None     Source Type: Journal    
DOI: 10.2217/bmm.09.79     Document Type: Review

References (124)

1. Gabrielli A, Avvedimento EV, Krieg T: Scleroderma. N. Engl. J. Med. 360, 1989-2003 (2009).
2. Bolster MB, Silver RM: Clinical features of systemic sclerosis. In: Rheumatology. Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH (Eds). Mosby Elsevier, Philadelphia, PA, USA 1375-1385 (2008).
3. Jimenez SA, Derk CT: Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann. Int. Med. 140, 37-50 (2004).
4. Varga J, Abraham D: Systemic sclerosis: a prototypic multisystem fbrotic disorder. J. Clin. Invest. 117, 557-567 (2007).
5. Medsger TA Jr: Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being. Rheum. Dis. Clin. North Am. 29, 255-273 (2003).
6. Meyer OC, Fertig N, Lucas M, Somogyi N, Medsger TA Jr: Disease subsets, antinuclear antibody profle, and clinical features in 127 French and 247 US adult patients with systemic sclerosis. J. Rheumatol. 34, 104-109 (2007).
7. Perera A, Fertig N, Lucas M et al.: Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with antitopoisomerase I antibody. Arthritis Rheum. 56, 2740-2746 (2007).
8. Abraham DJ, Varga J: Scleroderma: from cell and molecular mechanisms to disease models. Trends Immunol. 26, 587-595 (2005).
9. Fleming JN, Schwartz SM: The pathology of scleroderma vascular disease. Rheum. Dis. Clin. North Am. 34, 41-55 (2008).
10. Kahaleh B: Vascular disease in scleroderma: mechanisms of vascular injury. Rheum. Dis. Clin. North Am. 34, 57-71 (2008).
11. Mulligan-Kehoe MJ, Simons M: Vascular disease in scleroderma: angiogenesis and vascular repair. Rheum. Dis. Clin. North Am. 34, 73-79 vi (2008).
12. Merkel PA, Clements PJ, Reveille JD et al.: Current status of outcome measure development for clinical trials in systemic sclerosis: report from OMERACT 6. J. Rheumatol. 30, 1630-1647 (2003).
13. Furst DE, Khanna D, Mattucci-Cerinic M et al.: Scleroderma-developing measures of response. J. Rheumatol. 32, 2477-2480 (2005).
14. Gazi H, Pope JE, Clements P et al.: Outcome measurements in scleroderma: results from a delphi exercise. J. Rheumatol. 34, 501-509 (2007).
15. Hudson M, Steele R, Baron M, Canadian Scleroderma Research Group (CSRG): Update on indices of disease activity in systemic sclerosis. Semin. Arthritis Rheum. 37, 93-98 (2007).
16. Khanna D, Merkel PA: Outcome measures in systemic sclerosis: an update on instruments and current research. Curr. Rheumatol. Rep. 9, 151-157 (2007).
17. Feng Q, Yu M, Kiviat NB: Molecular biomarkers for cancer detection in blood and bodily fuids. Crit. Rev. Clin. Lab. Sci. 43, 497-560 (2006).
18. Jain KK: Cancer biomarkers: current issues and future directions. Curr. Opin. Mol. Ther. 9, 563-571 (2007).
19. Vittorini S, Clerico A: Cardiovascular biomarkers: increasing impact of laboratory medicine in cardiology practice. Clin. Chem. Lab. Med. 46, 748-763 (2008).
20. May A, Wang TJ: Biomarkers for cardiovascular disease: challenges and future directions. Trends Mol. Med. 14, 261-267 (2008).
21. McHugh NJ, Distler O, Giacomelli R, Riemekasten G: Non organ based laboratory markers in systemic sclerosis. Clin. Exp. Rheumatol. 21, S32-S38 (2003).
22. Pollard KM, Reimer G, Tan EM: Autoantibodies in scleroderma. Clin. Exp. Rheumatol. 7, x57-x62 (1989).
23. Steen VD: Autoantibodies in systemic sclerosis. Semin. Arthritis Rheum. 35, 35-42 (2005).
24. Ho K T, Reveille JD: The clinical relevance of autoantibodies in scleroderma. Arthritis Res. Ther. 5, 80-93 (2003).
25. Koenig M, Dieudé M, Senécal JL: Predictive value of antinuclear autoantibodies: the lessons of the systemic sclerosis autoantibodies. Autoimmun. Rev. 7, 588-593 (2008).
26. Basu D, Reveille JD: Anti-scl-70. Autoimmunity 38, 65-72 (2005).
27. Czömpöly T, Simon D, Czirják L, Németh P: Antitopoisomerase I autoantibodies in systemic sclerosis. Autoimmun. Rev. 8, 692-696 (2009).
28. Kallenberg CG: Anti-centromere antibodies (ACA). Clin. Rheumatol. 9, S136-S139 (1990).
29. Derk C T, Jimenez SA: Systemic sclerosis: current views of its pathogenesis. Autoimmun. Rev. 2, 181-191 (2003).
30. Meyer O: Prognostic markers for systemic sclerosis. Joint Bone Spine 73, 490-494 (2006).
31. Grassegger A, Pohla-Gubo G, Frauscher M, Hintner H: Autoantibodies in systemic sclerosis (scleroderma): clues for clinical evaluation. Wien. Med. Wochenschr. 158, 19-28 (2008).
32. Ferri C, Bernini L, Cecchetti R et al.: Cutaneous and serologic subsets of systemic sclerosis. J. Rheumatol. 18, 1826-1832 (1991).
33. Jacobsen S, Ullman S, Shen GQ, Wiik A, Halberg P: Infuence of clinical features, serum antinuclear antibodies, and lung function on survival of patients with systemic sclerosis. J. Rheumatol. 28, 2454-2459 (2001).
34. Shand L, Lunt M, Nihtyanova S et al.: Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis. Arthritis Rheum. 56, 2422-2431 (2007).
35. LeRoy EC: Systemic sclerosis. A vascular perspective. Rheum. Dis. Clin. North Am. 22, 695-708 (1996).
36. 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. 94, 482-484 (1981).
37. Wigley M: Vascular disease in scleroderma. Clin. Rev. Allergy Immunol. 36, 150-175 (2009).
38. Koch AE, Distler O: Vasculopathy and disordered angiogenesis in selected rheumatic diseases: rheumatoid arthritis and systemic sclerosis. Arthritis Res. Ther. 9(Suppl. 2), S3 (2007).
39. Herrick AL, Illingworth K, Blann A, Hay CR, Hollis S, Jayson MI: von Willebrand factor, thrombomodulin and markers of fbrinolysis in primary Raynaud's phenomenon and systemic sclerosis. Ann. Rheum. Dis. 55, 122-127 (1996).
40. Cerinic MM, Valentini G, Sorano GG et al.: Blood coagulation, fbrinolysis, and markers of endothelial dysfunction in systemic sclerosis. Semin. Arthritis Rheum. 32, 285-295 (2003).
41. 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. 24, 111-116 (2005).
42. Davies CA, Jeziorska M, Freemont AJ, Herrick A: The differential expression of VEGF, VEGFR-2, and GLUT-1 proteins in disease subtypes of systemic sclerosis. Hum. Pathol. 37, 190-197 (2006).
43. Hummers K: Microvascular damage in systemic sclerosis: detection and monitoring with biomarkers. Curr. Rheumatol. Rep. 8, 131-137 (2006).
44. Scheja A, Akesson A, Geborek P et al.: Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma). Arthritis Res. 3, 178-182 (2001).
45. Kumánovics G, Minier T, Radics J, Pálinkás L, Berki T, Czirják L: Comprehensive investigation of novel serum markers of pulmonary fbrosis associated with systemic sclerosis and dermato/polymyositis. Clin. Exp. Rheumatol. 26, 414-420 (2008).
46. 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 88, 914-918 (2003).
47. Braun-Moscovici Y, Nahir AM, Balbir-Gurman A: Endothelin and pulmonary arterial hypertension. Semin. Arthritis Rheum. 34, 442-453 (2004).
48. Sticherling M: The role of endothelin in connective tissue disease. Rheumatology (Oxford) 45(Suppl. 3), iii8-10 (2006).
49. Abraham D, Distler O: How does endothelial cell injury start? The role of endothelin in systemic sclerosis. Arthritis Res. Ther. 9, S2 (2007).
50. Yamane K, Kashiwagi H, Suzuki N et al.: Elevated plasma levels of endothelin-1 in systemic sclerosis. Arthritis Rheum. 34, 243-244 (1991).
51. 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 fbrotic lung disease. Am. J. Pathol. 151, 831-841 (1997).
52. Blann ED, Herrick A, Jayson MI: Altered levels of soluble adhesion molecules in rheumatoid arthritis, vasculitis and systemic sclerosis. Br. J. Rheumatol. 34, 814-819 (1995).
53. 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. 38, 184-189 (1995).
54. Ihn H, Sato S, Fujimoto M, Takehara K, Tamaki K: Increased serum levels of soluble vascular cell adhesion molecule-1 and E-selectin in patients with systemic sclerosis. Br. J. Rheumatol. 37, 1188-1192 (1998).
55. Denton CP, Bickerstaff MC, Shiwen X et al.: Serial circulating adhesion molecule levels refect disease severity in systemic sclerosis. Br. J. Rheumatol. 34, 1048-1054 (1995).
56. 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 fngertip ulcers. Arthritis Res. 4, R11 (2002).
57. Choi JJ, Min DJ, Cho ML et al.: Elevated vascular endothelial growth factor in systemic sclerosis. J. Rheumatol. 30, 1529-1533 (2003).
58. Chitale S, Al-Mowallad AF, Wang Q, Kumar S, Herrick A: High circulating levels of VEGF-C suggest abnormal lymphangiogenesis in systemic sclerosis. Rheumatology (Oxford) 47, 1727-1728 (2008).
59. Viac J, Schmitt D, Claudy A: Plasma vascular endothelial growth factor levels in scleroderma are not correlated with disease activity. Acta Derm. Venereol. 80, 383 (2000).
60. McLaughlin V, Humbert M, Coghlan G, Nash P, Steen V: Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology 48, iii25-31 (2009).
61. Ramirez A, Varga J: Pulmonary arterial hypertension in systemic sclerosis: clinical manifestations, pathophysiology, evaluation, and management. Treat. Respir. Med. 3, 339-352 (2004).
62. Steen VD, Medsger TA: Changes in causes of death in systemic sclerosis, 1972-2002. Ann. Rheum. Dis. 66, 940-944 (2007).
63. Schmidt J, Launay D, Soudan B et al.: Assessment of plasma endothelin level measurement in systemic sclerosis. Rev. Med. Interne 28, 371-376 (2007).
64. 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. 27, 1485-1494 (2006).
65. 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. 58, 284-291 (2008).
66. Dimitroulas T, Giannakoulas G, Karvounis H et al.: N-terminal probrain natriuretic peptide as a biochemical marker in the evaluation of bosentan treatment in systemic-sclerosis-related pulmonary arterial hypertension. Clin. Rheumatol. 27, 655-658 (2008).
67. Simeoni S, Lippi G, Pucetti A et al.: N-terminal pro-BNP in sclerodermic patients on bosentan therapy for PAH. Rheumatol. Int. 28, 657-660 (2008).
68. Mathai SC, Bueso M, Hummers K et al.: Disproportionate elevation of NT-proBNP in scleroderma-related pulmonary hypertension. Eur. Respir. J. 35(1), 95-104 (2009).
69. Wells AU, Steen V, Valentini G: Pulmonary complications: one of the most challenging complications of systemic sclerosis. Rheumatology (Oxford) 48, iii40-4 (2009).
70. Prasse A, Müller-Ouernheim J: Non-invasive biomarkers in pulmonary fbrosis. Respirology 14, 788-795 (2009).
71. Kumánovics G, Minier T, Radics J, Pálinkás L, Berki T, Czirják L: Comprehensive investigation of novel serum markers of pulmonary fbrosis associated with systemic sclerosis and dermato/polymyositis. Clin. Exp. Rheumatol. 26, 414-420 (2008).
72. Yamane K, Ihn H, Kubo M et al.: Serum levels of KL-6 as a useful marker for evaluating pulmonary fbrosis in patients with systemic sclerosis. J. Rheumatol. 27, 930-934 (2000).
73. Sato S, Nagaoka T, Hasegawa M, Nishijima C, Takehara K: Elevated serum KL-6 levels in patients with systemic sclerosis: association with the severity of pulmonary fbrosis. Dermatology 200, 196-201 (2000).
74. Veselý R, Vargová V, Ravelli A et al.: Serum level of KL-6 as a marker of interstitial lung disease in patients with juvenile systemic sclerosis. J. Rheumatol. 31, 795-800 (2004).
75. Yanaba K, Hasegawa M, Hamaguchi Y, Fujimoto M, Takehara K, Sato S: Longitudinal ana lysis of serum KL-6 levels in patients with systemic sclerosis: association with the activity of pulmonary fbrosis. Clin. Exp. Rheumatol. 21, 429-436 (2003).
76. Takahashi H, Kuroki Y, Tanaka H et al.: Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis. Am. J. Respir. Crit. Care Med. 162, 258-263 (2000).
77. Asano Y, Ihn H, Yamane K et al.: Clinical signifcance of surfactant protein D as a serum marker for evaluating pulmonary fbrosis in patients with systemic sclerosis. Arthritis Rheum. 44, 1363-1369 (2001).
78. Hant FN, Ludwicka-Bradley A, Wang HJ et al.; Scleroderma Lung Study Research Group: Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J. Rheumatol. 36, 773-780 (2009).
79. 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 fbrosis. Arthritis Rheum. 52, 2889-2896 (2005).
80. Prasse A, Pechkovsky DV, Toews GB et al.: CCL18 as an indicator of pulmonary fbrotic activity in idiopathic interstitial pneumonias and systemic sclerosis. Arthritis Rheum. 56, 1685-1693 (2007).
81. La Montagna G, D'Angelo S, Valentini G: Cross-sectional evaluation of YKL-40 serum concentrations in patients with systemic sclerosis. Relationship with clinical and serological aspects of disease. J. Rheumatol. 30, 2147-2151 (2003).
82. Nordenbaek C, Johansen JS, Hallberg P et al.: High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Scand. J. Rheumatol. 34, 293-297 (2005).
83. Kraling BM, Maul GG, Jimenez SA: Mononuclear cellular infltrates in clinically involved skin from patients with systemic sclerosis of recent onset predominantly consists of monocytes/macrophages. Pathobiology 63, 48-56 (1995).
84. Sakkas LI, Xu B, Artlett CM, Lu S, Jimenez SA, Platsoucas CD: Oligoclonal. T cell expansion in the skin of patients with systemic sclerosis. J. Immunol. 168, 3649-3659 (2002).
85. Degiannis D, Seibold JR, Czarnecki M, Raskova J, Raska K Jr: Soluble interleukin-2 receptors in patients with systemic sclerosis. Clinical and laboratory correlations. Arthritis Rheum. 33, 375-380 (1990).
86. Steen VD, Engel EE, Charley MR, Medsger TA Jr: Soluble serum interleukin 2 receptors in patients with systemic sclerosis. J. Rheumatol. 23, 646-649 (1996).
87. Becvár R, Stork J, Pesáková V et al.: Clinical correlations of potential activity markers in systemic sclerosis. Ann. NY Acad. Sci. 1051, 404-412 (2005).
88. Majewski S, Wojas-Pelc A, Malejczyk M, Szymanska E, Jablonska S: Serum levels of soluble TNF a receptor type I and the severity of systemic sclerosis. Acta Derm. Venereol. 79, 207-210 (1999).
89. Gruschwitz MS, Albrecht M, Vieth G, Haustein UF: In situ expression and serum levels of tumor necrosis factor-a receptors in patients with early stages of systemic sclerosis. J. Rheumatol. 24, 1936-1943 (1997).
90. Carulli MT, Handler C, Coghlan JG, Black CM, Denton CP: Can CCL2 serum levels be used in risk stratifcation or to monitor treatment response in systemic sclerosis? Ann. Rheum. Dis. 67, 105-109 (2008).
91. Antonelli A, Ferri C, Fallahi P et al.: CXCL10a and CCL2b chemokines in systemic sclerosis-a longitudinal study. Rheumatology (Oxford) 47, 45-49 (2008).
92. Komura K, Fujimoto M, Matsushita T et al.: Increased serum soluble CD40 levels in patients with systemic sclerosis. J. Rheumatol. 34, 353-358 (2007).
93. Allanore Y, Borderie D, Meune C et al.: Increased plasma soluble CD40 ligand concentrations in systemic sclerosis and association with pulmonary arterial hypertension and digital ulcers. Ann. Rheum. Dis. 64, 481-483 (2005).
94. Wuttge DM, Wildt M, Geborek P, Wollheim FA, Scheja A, Akesson A: Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease. Arthritis Res. Ther. 9, R85 (2007).
95. Komura K, Fujimoto M, Hasegawa M et al.: Increased serum interleukin 23 in patients with systemic sclerosis. J. Rheumatol. 35, 120-125 (2008).
96. Matsushita T, Hasegawa M, Yamaba K, Kodera M, Takehara K, Sato S: Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes Arthritis Rheum. 54, 192-201 (2006). (Pubitemid 43122202)
97. Matsushita T, Fujimoto M, Hasegawa M et al.: Elevated serum APRIL levels in patients with systemic sclerosis: distinct profles of systemic sclerosis categorized by APRIL and BAFF. J. Rheumatol. 34, 2056-2062 (2007).
98. Prud'homme GJ: Pathobiology of transforming growth factor b in cancer, fbrosis and immunologic disease, and therapeutic considerations. Lab. Invest. 8 7, 1077-1091 (2007).
99. Varga J, Whitfeld ML: Transforming growth factor-b in systemic sclerosis (scleroderma). Front. Biosci. 81, 226-235 (2009).
100. Varga J, Pasche B: Transforming growth factor b as a therapeutic target in systemic sclerosis. Nat. Rev. Rheumatol. 5, 200-206 (2009).
101. Leask A, Holmes A, Abraham DJ: Connective tissue growth factor: a new and important player in the pathogenesis of fbrosis. Curr. Rheumatol. Rep. 4, 136-142 (2002).
102. Dziadzio M, Smith RE, Abraham DJ, Black CM, Denton CP: Circulating levels of active transforming growth factor b1 are reduced in diffuse cutaneous systemic sclerosis and correlate with the modifed Rodnan skin score. Rheumatology (Oxford) 44, 1518-1524 (2005).
103. Dziadzio M, Usinger W, Leask A et al.: N-terminal connective tissue growth factor is a marker of the fbrotic phenotype in scleroderma. Q. J. Med. 98, 485-492 (2005).
104. Hunzelmann N, Risteli J, Risteli L et al.: Circulating type I collagen degradation products: a new serum marker for clinical severity in patients with scleroderma? Br. J. Dermatol. 139, 1020-1025 (1998).
105. Allanore Y, Borderie D, Lemaréchal H, Cherruau B, Ekindjian OG, Kahan A: Correlation of serum collagen I carboxyterminal telopeptide concentrations with cutaneous and pulmonary involvement in systemic sclerosis. J. Rheumatol. 30, 68-73 (2003).
106. Black CM, McWhirter A, Harrison NK, Kirk JM, Laurent GJ: Serum type III procollagen peptide concentrations in systemic sclerosis and Raynaud's phenomenon: relationship to disease activity and duration. Br. J. Rheumatol. 28, 98-103 (1989).
107. Becvár R, Stork J, Pesáková V et al.: Clinical correlations of potential activity markers in systemic sclerosis. Ann. NY Acad. Sci. 1051, 404-412 (2005).
108. Becvár R, Hulejová H, Braun M, Stork J: Collagen degradation products and proinfammatory cytokines in systemic and localized scleroderma. Folia Biol. (Praha) 53, 66-68 (2007).
109. Nagy Z, Czirják L: Increased levels of amino terminal propeptide of type III procollagen are an unfavorable predictor of survival in systemic sclerosis. Clin. Exp. Rheumatol. 23, 165-172 (2005).
110. 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, 1242-1248 (2008).
111. Farina G, Lemaire R, Korn JH, Widom RL: Cartilage oligomeric matrix protein is overexpressed by scleroderma dermal fbroblasts. Matrix Biol. 25, 213-222 (2006).
112. Farina G, Lemaire R, Pancari P, Bayle J, Widom RL, Lafyatis R: Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fbroblast responses to transforming growth factor b. Ann. Rheum. Dis. 68, 435-441 (2009).
113. Whitfeld ML, Finlay DR, Murray JI et al.: Systemic and cell type-specifc gene expression patterns in scleroderma skin. Proc. Natl Acad. Sci. USA 100, 12319-12324 (2003).
114. Tan FK, Hildebrand BA, Lester MS et al.: Classifcation ana lysis of the transcriptosome of nonlesional cultured dermal fbroblasts from systemic sclerosis patients with early disease. Arthritis Rheum. 52, 865-876 (2005).
115. Gardner H, Shearstone JR, Bandaru R et al.: Gene profling of scleroderma skin reveals robust signatures of disease that are imperfectly refected in the transcript profles of explanted fbroblasts. Arthritis Rheum. 54, 1961-1973 (2006).
116. Pendergrass SA, Whitfeld ML, Gardner H: Understanding systemic sclerosis through gene expression profling. Curr. Opin. Rheumatol. 19, 561-567 (2007).
117. Milano A, Pendergrass SA, Sargent JL et al.: Molecular subsets in the gene expression signatures of scleroderma skin. PLoS ONE 3, e2696 (2008).
118. Bos CL, van Baarsen LG, Timmer TC et al.: Molecular subtypes of systemic sclerosis in association with anticentromere antibodies and digital ulcers. Genes Immun. 10, 210-218 (2009).
119. Renzoni EA, Abraham DJ, Howat S et al.: Gene expression profling reveals novel TGFb targets in adult lung fbroblasts. Respir. Res. 5, 24 (2004).
120. Grigoryev DN, Mathai SC, Fisher MR et al.: Identifcation of candidate genes in scleroderma-related pulmonary arterial hypertension. Transl. Res. 151, 197-207 (2008).
121. Sargent JL, Milano A, Bhattacharyya S et al.: A TGFb-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity. J. Invest. Dermatol. doi: 10.1038/jid.2009.318 (2009) (Epub ahead of print).
122. Chung L, Fiorentino DF, Benbarak MJ et al.: Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheum. 60, 584-591 (2009).
123. Aden N, Shiwen X, Aden D et al.: Proteomic ana lysis of scleroderma lesional skin reveals activated wound healing phenotype of epidermal cell layer. Rheumatology 47, 1754-1760 (2008).
124. Bogatkevish GS, Ludwicka-Bradley A, Singleton CB, Bethard JR, Silver RM: Proteomic ana lysis of CTGF-activated lung fbroblasts: identifcation of IQGAP1 as a key player in lung fbroblast migration. Am. J. Physiol. Lung Cell Mol. Physiol. 295, L603-L611 (2008).