Skip to main content
Erschienen in: Journal of Clinical Immunology 6/2014

01.08.2014 | Original Research

Early Systemic Sclerosis: Serum Profiling of Factors Involved in Endothelial, T-cell, and Fibroblast Interplay is Marked by Elevated Interleukin-33 Levels

verfasst von: Serena Vettori, Giovanna Cuomo, Michele Iudici, Virginia D’Abrosca, Veronica Giacco, Giusi Barra, Raffaele De Palma, Gabriele Valentini

Erschienen in: Journal of Clinical Immunology | Ausgabe 6/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud’s phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients.

Methods

Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities.

Results

Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p < 0.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p < 0.01) and definite SSc patients (p < 0.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed.

Conclusions

Our study suggests that an endothelial, T-cell and fibroblast activation can be present in patients with early SSc and it is associated with a distinct profile of circulating factors involved in the cross-talk of these cells. The marked increase of IL-33 in early SSc patients suggests new routes of investigation of cell-cell dynamics in target tissues predating overt disease manifestations, thus opening to new therapeutic approaches.
Literatur
1.
Zurück zum Zitat Gu YS, Kong J, Cheema GS, Keen CL, Wick G, Gershwin ME. The immunobiology of systemic sclerosis. Semin Arthritis Rheum. 2008;38:132–60.PubMedCrossRef Gu YS, Kong J, Cheema GS, Keen CL, Wick G, Gershwin ME. The immunobiology of systemic sclerosis. Semin Arthritis Rheum. 2008;38:132–60.PubMedCrossRef
2.
Zurück zum Zitat Fleischmajer R, Perlish JS. The pathophysiology of the fibrosis in scleroderma skin. Prog Clin Biol Res. 1984;154:381–404.PubMed Fleischmajer R, Perlish JS. The pathophysiology of the fibrosis in scleroderma skin. Prog Clin Biol Res. 1984;154:381–404.PubMed
4.
Zurück zum Zitat De Palma R, D’Aiuto E, Vettori S, Cuoppolo PP, Abbate G, Valentini G. Peripheral T cells from early systemic sclerosis patients kill autologous fibroblasts in co-culture: is T-cell response aimed to play a protective role? Rheumatology (Oxford). 2010;49:1257–66.CrossRef De Palma R, D’Aiuto E, Vettori S, Cuoppolo PP, Abbate G, Valentini G. Peripheral T cells from early systemic sclerosis patients kill autologous fibroblasts in co-culture: is T-cell response aimed to play a protective role? Rheumatology (Oxford). 2010;49:1257–66.CrossRef
5.
Zurück zum Zitat Valentini G, Cuomo G, Abignano G, Petrillo A, Vettori S, Capasso A, et al. Early systemic sclerosis: assessment of clinical and pre-clinical organ ivolvement in patients with different disease features. Rheumatology (Oxford). 2011;50:317–23.CrossRef Valentini G, Cuomo G, Abignano G, Petrillo A, Vettori S, Capasso A, et al. Early systemic sclerosis: assessment of clinical and pre-clinical organ ivolvement in patients with different disease features. Rheumatology (Oxford). 2011;50:317–23.CrossRef
6.
Zurück zum Zitat Valentini G, Marcoccia A, Cuomo G, Vettori S, Iudici M, Bondanini F, et al. Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers. Arthritis Res Ther. 2013;15:R63.PubMedCentralPubMedCrossRef Valentini G, Marcoccia A, Cuomo G, Vettori S, Iudici M, Bondanini F, et al. Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers. Arthritis Res Ther. 2013;15:R63.PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat 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; 23:581–90 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; 23:581–90
8.
Zurück zum Zitat Van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arthritis Rheum. 2013;65:2737–47.PubMedCrossRef Van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arthritis Rheum. 2013;65:2737–47.PubMedCrossRef
9.
Zurück zum Zitat LeRoy EC, Black CM, Fleichmajer R, Jablonksa S, Krieg T, Medsger Jr TA, et al. Scleroderma (systemic sclerosis). Classification, subset and pathogenesis. J Rheumatol. 1988;15:202–5.PubMed LeRoy EC, Black CM, Fleichmajer R, Jablonksa S, Krieg T, Medsger Jr TA, et al. Scleroderma (systemic sclerosis). Classification, subset and pathogenesis. J Rheumatol. 1988;15:202–5.PubMed
10.
Zurück zum Zitat Cappelli S, Bellando Randone S, Martinovic D, Tamas MM, Pasalic K, Allanore Y, et al. “To be or not to be,” ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum. 2012;41:589–98.PubMedCrossRef Cappelli S, Bellando Randone S, Martinovic D, Tamas MM, Pasalic K, Allanore Y, et al. “To be or not to be,” ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum. 2012;41:589–98.PubMedCrossRef
11.
Zurück zum Zitat Yoshizaki A, Yanaba K, Iwata Y, Komura K, Ogawa A, Akiyama Y, et al. Cell adhesion molecole regulate fibrotic process via Th1/Th2/Th17 cell balance in a bleomycin-induced scleroderma model. J Immunol. 2010;185:2502–15.PubMedCentralPubMedCrossRef Yoshizaki A, Yanaba K, Iwata Y, Komura K, Ogawa A, Akiyama Y, et al. Cell adhesion molecole regulate fibrotic process via Th1/Th2/Th17 cell balance in a bleomycin-induced scleroderma model. J Immunol. 2010;185:2502–15.PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Codullo V, Baldwin HM, Singh MD, Fraser AR, Wilson C, Gilmour A, et al. An investigation of the inflammatory cytokine and chemokine network in systemic sclerosis. Ann Rheum Dis. 2011;70:1115–21.PubMedCrossRef Codullo V, Baldwin HM, Singh MD, Fraser AR, Wilson C, Gilmour A, et al. An investigation of the inflammatory cytokine and chemokine network in systemic sclerosis. Ann Rheum Dis. 2011;70:1115–21.PubMedCrossRef
14.
Zurück zum Zitat Rankin AL, Mumm JB, Murphy E, Turner S, Yu N, McClanahan TK, et al. IL-33 induces IL-13-dependent cutaneous fibrosis. J Immunol. 2010;184:1526–35.PubMedCrossRef Rankin AL, Mumm JB, Murphy E, Turner S, Yu N, McClanahan TK, et al. IL-33 induces IL-13-dependent cutaneous fibrosis. J Immunol. 2010;184:1526–35.PubMedCrossRef
15.
Zurück zum Zitat Varga J, Whitfield ML. Transforming growth factor-beta in systemic sclerosis (scleroderma). Front Biosci (Schol Ed). 2009;1:226–35.CrossRef Varga J, Whitfield ML. Transforming growth factor-beta in systemic sclerosis (scleroderma). Front Biosci (Schol Ed). 2009;1:226–35.CrossRef
16.
Zurück zum Zitat 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;24:111–6.PubMedCrossRef 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;24:111–6.PubMedCrossRef
17.
Zurück zum Zitat Denton CP, Bickerstaff MC, Shiwen X, Carulli MT, Haskard DO, Dubois RM, et al. Serial circulating adhesion molecule levels reflect disease severity in systemic sclerosis. Br J Rheumatol. 1995;34:1048–54.PubMedCrossRef Denton CP, Bickerstaff MC, Shiwen X, Carulli MT, Haskard DO, Dubois RM, et al. Serial circulating adhesion molecule levels reflect disease severity in systemic sclerosis. Br J Rheumatol. 1995;34:1048–54.PubMedCrossRef
18.
Zurück zum Zitat Snowden N, Coupes B, Herrick A, Illingworth K, Jayson MI, Brenchley PE. Plasma TGF-beta in systemic sclerosis: a cross sectional study. Ann Rheum Dis. 1994;53:763–7.PubMedCentralPubMedCrossRef Snowden N, Coupes B, Herrick A, Illingworth K, Jayson MI, Brenchley PE. Plasma TGF-beta in systemic sclerosis: a cross sectional study. Ann Rheum Dis. 1994;53:763–7.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat 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;44:1518–24.CrossRef 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;44:1518–24.CrossRef
20.
Zurück zum Zitat Wolf SI, Howat S, Abraham DJ, Pearson JD, Lawson C. Agonistic anti-ICAM-1 antibodies in scleroderma: activation of endothelial pro-inflammatory cascade. Vasc Pharmacol. 2013;59:19–26.CrossRef Wolf SI, Howat S, Abraham DJ, Pearson JD, Lawson C. Agonistic anti-ICAM-1 antibodies in scleroderma: activation of endothelial pro-inflammatory cascade. Vasc Pharmacol. 2013;59:19–26.CrossRef
21.
22.
Zurück zum Zitat Wynn T. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;241:199–210.CrossRef Wynn T. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;241:199–210.CrossRef
23.
Zurück zum Zitat Van de Veerdonk FL, Netea MG. New insights in the immunobiology of IL-1 family members. Front Immunol. 2013;4:167.PubMedCentralPubMed Van de Veerdonk FL, Netea MG. New insights in the immunobiology of IL-1 family members. Front Immunol. 2013;4:167.PubMedCentralPubMed
24.
Zurück zum Zitat Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23:479–90.PubMedCrossRef Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23:479–90.PubMedCrossRef
25.
Zurück zum Zitat Chackarian AA, Oldham ER, Murphy EE, Schimtz J, Pflanz S, Kastelein RA, et al. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J Immunol. 2007;179:2551–5. Chackarian AA, Oldham ER, Murphy EE, Schimtz J, Pflanz S, Kastelein RA, et al. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J Immunol. 2007;179:2551–5.
26.
Zurück zum Zitat Manetti M, Guiducci S, Ceccarelli C, Romano E, Bellando-Randone S, Conforti ML, et al. Increased circulating levels of interleukin 33 in sistemic sclerosis correlate with early disease stage and microvascular involvement. Ann Rheum Dis. 2011;70:1876–8.PubMedCrossRef Manetti M, Guiducci S, Ceccarelli C, Romano E, Bellando-Randone S, Conforti ML, et al. Increased circulating levels of interleukin 33 in sistemic sclerosis correlate with early disease stage and microvascular involvement. Ann Rheum Dis. 2011;70:1876–8.PubMedCrossRef
27.
Zurück zum Zitat Terras S, Opitz E, Moritz RKC, Höxtermann S, Gambichler T, Kreuter A. Increased serum IL-33 levels may indicate vascular involvement in systemic sclerosis. Ann Rheum Dis. 2013;72:144–5.PubMedCrossRef Terras S, Opitz E, Moritz RKC, Höxtermann S, Gambichler T, Kreuter A. Increased serum IL-33 levels may indicate vascular involvement in systemic sclerosis. Ann Rheum Dis. 2013;72:144–5.PubMedCrossRef
28.
Zurück zum Zitat Manetti M, Ibba-Manneschi L, Liakouli V, Guiducci S, Milia AF, Benelli G, et al. The IL1-like cytokine IL-33 and its receptor ST2 are abnormally espresse in the affected skin and visceral organs of patients with systemic sclerosis. Ann Rheum Dis. 2010;69:598–605.PubMedCrossRef Manetti M, Ibba-Manneschi L, Liakouli V, Guiducci S, Milia AF, Benelli G, et al. The IL1-like cytokine IL-33 and its receptor ST2 are abnormally espresse in the affected skin and visceral organs of patients with systemic sclerosis. Ann Rheum Dis. 2010;69:598–605.PubMedCrossRef
Metadaten
Titel
Early Systemic Sclerosis: Serum Profiling of Factors Involved in Endothelial, T-cell, and Fibroblast Interplay is Marked by Elevated Interleukin-33 Levels
verfasst von
Serena Vettori
Giovanna Cuomo
Michele Iudici
Virginia D’Abrosca
Veronica Giacco
Giusi Barra
Raffaele De Palma
Gabriele Valentini
Publikationsdatum
01.08.2014
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 6/2014
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-014-0037-0

Weitere Artikel der Ausgabe 6/2014

Journal of Clinical Immunology 6/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.