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Published in: Arthritis Research & Therapy 3/2013

Open Access 01-06-2013 | Research article

Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers

Authors: Gabriele Valentini, Antonella Marcoccia, Giovanna Cuomo, Serena Vettori, Michele Iudici, Francesco Bondanini, Carlo Santoriello, Aldo Ciani, Domenico Cozzolino, Giovanni Maria De Matteis, Salvatore Cappabianca, Filiberto Vitelli, Alberto Spanò

Published in: Arthritis Research & Therapy | Issue 3/2013

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Abstract

Introduction

Early systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear.

Methods

Seventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation.

Results

Thirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies.

Conclusion

These results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.
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Literature
1.
go back to reference LeRoy EC, Medsger TA: Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001, 28: 1573-1576.PubMed LeRoy EC, Medsger TA: Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001, 28: 1573-1576.PubMed
2.
go back to reference Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, Goulet JR, Rich E, Grodzicky T, Raymond Y, Senécal JL: 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, 58: 3902-3912. 10.1002/art.24038.CrossRefPubMed Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, Goulet JR, Rich E, Grodzicky T, Raymond Y, Senécal JL: 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, 58: 3902-3912. 10.1002/art.24038.CrossRefPubMed
3.
go back to reference Valentini G, Cuomo G, Abignano G, Petrillo A, Vettori S, Capasso A, Cozzolino D, Del Genio G, Santoriello C: Early systemic sclerosis: assessment of clinical and pre-clinical organ involvement in patients with different disease features. Rheumatology (Oxford). 2011, 50: 317-323. 10.1093/rheumatology/keq176.CrossRef Valentini G, Cuomo G, Abignano G, Petrillo A, Vettori S, Capasso A, Cozzolino D, Del Genio G, Santoriello C: Early systemic sclerosis: assessment of clinical and pre-clinical organ involvement in patients with different disease features. Rheumatology (Oxford). 2011, 50: 317-323. 10.1093/rheumatology/keq176.CrossRef
4.
go back to reference Valentini G, Vettori S, Cuomo G, Iudici M, D'Abrosca V, Capocotta D, Del Genio G, Santoriello C, Cozzolino D: Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement. Arthritis Res Ther. 2012, 14: R188-10.1186/ar4019.PubMedCentralCrossRefPubMed Valentini G, Vettori S, Cuomo G, Iudici M, D'Abrosca V, Capocotta D, Del Genio G, Santoriello C, Cozzolino D: Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement. Arthritis Res Ther. 2012, 14: R188-10.1186/ar4019.PubMedCentralCrossRefPubMed
5.
go back to reference Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary criteria for classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980, 23: 581-590. 10.1002/art.1780230510.CrossRef Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary criteria for classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980, 23: 581-590. 10.1002/art.1780230510.CrossRef
6.
go back to reference LeRoy EC, Medsger TA: Raynaud's phenomenon: a proposal for classification. Clin Exp Rheumatol. 1992, 10: 485-488.PubMed LeRoy EC, Medsger TA: Raynaud's phenomenon: a proposal for classification. Clin Exp Rheumatol. 1992, 10: 485-488.PubMed
7.
go back to reference Sebastiani M, Manfredi A, Vukatana G, Moscatelli S, Riato L, Bocci M, Iudici M, Principato A, Mazzuca S, Del Medico P, De Angelis R, D'Amico R, Vicini R, Colaci M, Ferri C: Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study. Ann Rheum Dis. 2012, 71: 67-70. 10.1136/annrheumdis-2011-200022.CrossRefPubMed Sebastiani M, Manfredi A, Vukatana G, Moscatelli S, Riato L, Bocci M, Iudici M, Principato A, Mazzuca S, Del Medico P, De Angelis R, D'Amico R, Vicini R, Colaci M, Ferri C: Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study. Ann Rheum Dis. 2012, 71: 67-70. 10.1136/annrheumdis-2011-200022.CrossRefPubMed
8.
go back to reference Maricq HR: Widefield capillary microscopy: technique and rating scale for abnormalities seen in scleroderma and related disorders. Arthritis Rheum. 1981, 24: 1159-1165. 10.1002/art.1780240907.CrossRefPubMed Maricq HR: Widefield capillary microscopy: technique and rating scale for abnormalities seen in scleroderma and related disorders. Arthritis Rheum. 1981, 24: 1159-1165. 10.1002/art.1780240907.CrossRefPubMed
9.
go back to reference Scussel-Lonzetti L, Joyal F, Raynauld J-P, Roussin A, Rich E, Goulet JR, Raymond Y, Senécal JL: Predicting mortality in systemic sclerosis. Analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore). 2002, 81: 154-167. 10.1097/00005792-200203000-00005.CrossRef Scussel-Lonzetti L, Joyal F, Raynauld J-P, Roussin A, Rich E, Goulet JR, Raymond Y, Senécal JL: Predicting mortality in systemic sclerosis. Analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore). 2002, 81: 154-167. 10.1097/00005792-200203000-00005.CrossRef
10.
go back to reference Caramaschi P, Canestrini S, Martinelli N, Volpe A, Pieropan S, Ferrari M, Bambara LM, Carletto A, Biasi D: Scleroderma patients nailfold videocapillaroscopic patterns are associated with disease subset and disease severity. Rheumatology. 2007, 46: 1566-1569. 10.1093/rheumatology/kem190.CrossRefPubMed Caramaschi P, Canestrini S, Martinelli N, Volpe A, Pieropan S, Ferrari M, Bambara LM, Carletto A, Biasi D: Scleroderma patients nailfold videocapillaroscopic patterns are associated with disease subset and disease severity. Rheumatology. 2007, 46: 1566-1569. 10.1093/rheumatology/kem190.CrossRefPubMed
11.
go back to reference Nishimura RA, Miller FA, Callahan MJ, Benassi RC, Seward JB, Tajik AS: Doppler echocardiography: theory, instrumentation, technique and application. Mayo Clin Proc. 1985, 60: 321-343. 10.1016/S0025-6196(12)60540-0.CrossRefPubMed Nishimura RA, Miller FA, Callahan MJ, Benassi RC, Seward JB, Tajik AS: Doppler echocardiography: theory, instrumentation, technique and application. Mayo Clin Proc. 1985, 60: 321-343. 10.1016/S0025-6196(12)60540-0.CrossRefPubMed
12.
go back to reference Maione S, Cuomo G, Giunta A, Tanturri de Horatio L, La Montagna G, Manguso F, Alagia I, Valentini G: Echocardiographic alterations in systemic sclerosis. A longitudinal study. Semin Arthritis Rheum. 2005, 34: 721-727. 10.1016/j.semarthrit.2004.11.001.CrossRefPubMed Maione S, Cuomo G, Giunta A, Tanturri de Horatio L, La Montagna G, Manguso F, Alagia I, Valentini G: Echocardiographic alterations in systemic sclerosis. A longitudinal study. Semin Arthritis Rheum. 2005, 34: 721-727. 10.1016/j.semarthrit.2004.11.001.CrossRefPubMed
13.
go back to reference Ogilvie CM, Forster RE, Blakemore WS, Morton JW: A standardized breath holding technique for clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest. 1957, 36: 1-17. 10.1172/JCI103402.PubMedCentralCrossRefPubMed Ogilvie CM, Forster RE, Blakemore WS, Morton JW: A standardized breath holding technique for clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest. 1957, 36: 1-17. 10.1172/JCI103402.PubMedCentralCrossRefPubMed
14.
go back to reference Steen VD, Owens GR, Fino GJ, Rodnan GP, Medsger TA: Pulmonary involvement in systemic sclerosis (scleroderma). Arthritis Rheum. 1985, 28: 759-767. 10.1002/art.1780280706.CrossRefPubMed Steen VD, Owens GR, Fino GJ, Rodnan GP, Medsger TA: Pulmonary involvement in systemic sclerosis (scleroderma). Arthritis Rheum. 1985, 28: 759-767. 10.1002/art.1780280706.CrossRefPubMed
15.
go back to reference Kazerooni EA, Martinez FJ, Flint A, Jamadar DA, Gross BH, Spizarny DL, Cascade PN, Whyte RI, Lynch JP, Toews G: Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. Am J Roentgenol. 1997, 169: 977-983. 10.2214/ajr.169.4.9308447.CrossRef Kazerooni EA, Martinez FJ, Flint A, Jamadar DA, Gross BH, Spizarny DL, Cascade PN, Whyte RI, Lynch JP, Toews G: Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. Am J Roentgenol. 1997, 169: 977-983. 10.2214/ajr.169.4.9308447.CrossRef
16.
go back to reference Walker UA, Tyndall A, Czirják L, Denton CP, Farge-Bancel D, Kowal-Bielecka O, Müller-Ladner U, Matucci-Cerinic M, EUSTAR co-authors: Geographical variation of disease manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials and Research (EUSTAR) group database. Ann Rheum Dis. 2009, 68: 856-862. 10.1136/ard.2008.091348.CrossRefPubMed Walker UA, Tyndall A, Czirják L, Denton CP, Farge-Bancel D, Kowal-Bielecka O, Müller-Ladner U, Matucci-Cerinic M, EUSTAR co-authors: Geographical variation of disease manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials and Research (EUSTAR) group database. Ann Rheum Dis. 2009, 68: 856-862. 10.1136/ard.2008.091348.CrossRefPubMed
17.
go back to reference Wells AU, Steen V, Valentini G: Pulmonary complications: one of the most challenging complications of systemic sclerosis. Rheumatology (Oxford). 2009, 48 (Suppl 3): 40-44. Wells AU, Steen V, Valentini G: Pulmonary complications: one of the most challenging complications of systemic sclerosis. Rheumatology (Oxford). 2009, 48 (Suppl 3): 40-44.
18.
go back to reference Scheja A, Wildt M, Wollheim FA, Akesson A, Saxne T: Circulating collagen metabolities in systemic sclerosis. Differences between limited and diffuse form and relationship with pulmonary involvement. Rheumatology. 2000, 39: 1110-1113. 10.1093/rheumatology/39.10.1110.CrossRefPubMed Scheja A, Wildt M, Wollheim FA, Akesson A, Saxne T: Circulating collagen metabolities in systemic sclerosis. Differences between limited and diffuse form and relationship with pulmonary involvement. Rheumatology. 2000, 39: 1110-1113. 10.1093/rheumatology/39.10.1110.CrossRefPubMed
19.
go back to reference Allanore Y, Borderie D, Lemaréchal H, Cherrau B, Ekindjian OG, Kahan A: Correlation of serum collagen I carboxyterminal telopeptide concentrations with cutaneous and and pulmonary involvement in systemic sclerosis. J Rheumatol. 2003, 30: 68-73.PubMed Allanore Y, Borderie D, Lemaréchal H, Cherrau B, Ekindjian OG, Kahan A: Correlation of serum collagen I carboxyterminal telopeptide concentrations with cutaneous and and pulmonary involvement in systemic sclerosis. J Rheumatol. 2003, 30: 68-73.PubMed
20.
go back to reference LeRoy EC, Maricq HR, Kahaleh MB: Undifferentiated connective tissue syndromes. Arthritis Rheum. 1980, 23: 341-343. 10.1002/art.1780230312.CrossRefPubMed LeRoy EC, Maricq HR, Kahaleh MB: Undifferentiated connective tissue syndromes. Arthritis Rheum. 1980, 23: 341-343. 10.1002/art.1780230312.CrossRefPubMed
21.
go back to reference 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. 1998, 37: 1188-1192. 10.1093/rheumatology/37.11.1188.CrossRefPubMed 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. 1998, 37: 1188-1192. 10.1093/rheumatology/37.11.1188.CrossRefPubMed
22.
go back to reference Degiannis D, Seibold JR, Czarnecki M, Raskova J, Raska K: Soluble interleukin-2 receptors in patients with systemic sclerosis. Clinical and laboratory correlations. Arthritis Rheum. 1990, 33: 375-380. 10.1002/art.1780330310.CrossRefPubMed Degiannis D, Seibold JR, Czarnecki M, Raskova J, Raska K: Soluble interleukin-2 receptors in patients with systemic sclerosis. Clinical and laboratory correlations. Arthritis Rheum. 1990, 33: 375-380. 10.1002/art.1780330310.CrossRefPubMed
23.
go back to reference Englert H, Champion D, Wu JC, Giallussi J, McGrath M, Manolios N: Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of 'prescleroderma'. Intern Med J. 2011, 41: 197-199. 10.1111/j.1445-5994.2010.02381.x.CrossRefPubMed Englert H, Champion D, Wu JC, Giallussi J, McGrath M, Manolios N: Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of 'prescleroderma'. Intern Med J. 2011, 41: 197-199. 10.1111/j.1445-5994.2010.02381.x.CrossRefPubMed
24.
go back to reference Moinzadeh Pia, Nihtyanova SI, Howell K, Ong VH, Denton CP: Impact of hallmark autoantibody reactivity on early diagnosis of scleroderma. Clin Rev Allergy Immunol. 2012, Moinzadeh Pia, Nihtyanova SI, Howell K, Ong VH, Denton CP: Impact of hallmark autoantibody reactivity on early diagnosis of scleroderma. Clin Rev Allergy Immunol. 2012,
25.
go back to reference Matucci-Cerinic M, Allanore Y, Czirják L, Tyndall A, Müller-Ladner U, Denton C, Valentini G, Distler O, Fligelstone K, Tyrrel-Kennedy A, Farge D, Kowal-Bielecka O, van den Hoogen F, Cutolo M, Sampaio-Barros PD, Nash P, Takehara K, Furst DE: The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy. Ann Rheum Dis. 2009, 68: 1377-1380. 10.1136/ard.2008.106302.CrossRefPubMed Matucci-Cerinic M, Allanore Y, Czirják L, Tyndall A, Müller-Ladner U, Denton C, Valentini G, Distler O, Fligelstone K, Tyrrel-Kennedy A, Farge D, Kowal-Bielecka O, van den Hoogen F, Cutolo M, Sampaio-Barros PD, Nash P, Takehara K, Furst DE: The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy. Ann Rheum Dis. 2009, 68: 1377-1380. 10.1136/ard.2008.106302.CrossRefPubMed
26.
go back to reference Avouac J, Fransen J, Walker UA, Riccieri V, Smith V, Muller C, Miniati I, Tarner IH, Randone SB, Cutolo M, Allanore Y, Distler O, Valentini G, Czirjak L, Müller-Ladner U, Furst DE, Tyndall A, Matucci-Cerinic M, EUSTAR Group: Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group. Ann Rheum Dis. 2011, 70: 476-481. 10.1136/ard.2010.136929.CrossRefPubMed Avouac J, Fransen J, Walker UA, Riccieri V, Smith V, Muller C, Miniati I, Tarner IH, Randone SB, Cutolo M, Allanore Y, Distler O, Valentini G, Czirjak L, Müller-Ladner U, Furst DE, Tyndall A, Matucci-Cerinic M, EUSTAR Group: Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group. Ann Rheum Dis. 2011, 70: 476-481. 10.1136/ard.2010.136929.CrossRefPubMed
27.
go back to reference Fransen J, Johnson SR, van den Hoogen F, Baron M, Allanore Y, Carreira PE, Czirják L, Denton CP, Distler O, Furst DE, Gabrielli A, Herrick A, Inanc M, Kahaleh B, Kowal-Bielecka O, Medsger TA, Mueller-Ladner U, Riemekasten G, Sierakowski S, Valentini G, Veale D, Vonk MC, Walker U, Chung L, Clements PJ, Collier DH, Csuka ME, Jimenez S, Merkel PA, Seibold JR, et al: Items for developing revised classification criteria in systemic sclerosis: results of a consensus exercise. Arthritis Care Res. 2012, 64: 351-357. 10.1002/acr.20679.CrossRef Fransen J, Johnson SR, van den Hoogen F, Baron M, Allanore Y, Carreira PE, Czirják L, Denton CP, Distler O, Furst DE, Gabrielli A, Herrick A, Inanc M, Kahaleh B, Kowal-Bielecka O, Medsger TA, Mueller-Ladner U, Riemekasten G, Sierakowski S, Valentini G, Veale D, Vonk MC, Walker U, Chung L, Clements PJ, Collier DH, Csuka ME, Jimenez S, Merkel PA, Seibold JR, et al: Items for developing revised classification criteria in systemic sclerosis: results of a consensus exercise. Arthritis Care Res. 2012, 64: 351-357. 10.1002/acr.20679.CrossRef
28.
go back to reference Johnson SR, Fransen J, Khanna D, Baron M, van den Hoogen F, Medsger TA, Peschken CA, Carreira PE, Riemekasten G, Tyndall A, Matucci-Cerinic M, Pope JE: Validation of potential classification criteria for systemic sclerosis. Arthritis Care Res. 2012, 64: 358-367. 10.1002/acr.20684.CrossRef Johnson SR, Fransen J, Khanna D, Baron M, van den Hoogen F, Medsger TA, Peschken CA, Carreira PE, Riemekasten G, Tyndall A, Matucci-Cerinic M, Pope JE: Validation of potential classification criteria for systemic sclerosis. Arthritis Care Res. 2012, 64: 358-367. 10.1002/acr.20684.CrossRef
Metadata
Title
Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers
Authors
Gabriele Valentini
Antonella Marcoccia
Giovanna Cuomo
Serena Vettori
Michele Iudici
Francesco Bondanini
Carlo Santoriello
Aldo Ciani
Domenico Cozzolino
Giovanni Maria De Matteis
Salvatore Cappabianca
Filiberto Vitelli
Alberto Spanò
Publication date
01-06-2013
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2013
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4236

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