Early systemic sclerosis: serum profiling of factors involved in endothelial, T-cell, and fibroblast interplay is marked by elevated interleukin-33 levels.
OBJECTIVE
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.
Rheumatology Unit, Second University of Naples, Via S. Pansini 5, 80131, Naples, Italy, serenavettori@libero.it.
Serena
S
Vettori
Giovanna
G
Cuomo
Michele
M
Iudici
Virginia
V
D'Abrosca
Veronica
V
Giacco
Giusi
G
Barra
Raffaele
R
De Palma
Gabriele
G
Valentini
D000328:Adult; D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002196:Capillaries / Q000473:pathology; D002450:Cell Communication; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D000067596:Interleukin-33; D016209:Interleukin-8 / Q000097:blood; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D020678:Microscopic Angioscopy; D008875:Middle Aged; D011928:Raynaud Disease / Q000175:diagnosis* / Q000276:immunology; D012595:Scleroderma, Systemic / Q000175:diagnosis* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000974:Antibodies, Antinuclear; D015415:Biomarkers; D018932:Chemokine CCL2; C506536:IL33 protein, human; D018793:Interleukin-13; D000067596:Interleukin-33; D016209:Interleukin-8; D007378:Interleukins; D018799:Intercellular Adhesion Molecule-1