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Earliest Phase of Systemic Sclerosis Typified by Increased Levels of Inflammatory Proteins in the Serum
Author(s) -
Cossu Marta,
Bon Lenny,
Preti Carlo,
Rossato Marzia,
Beretta Lorenzo,
Radstake Timothy R. D. J.
Publication year - 2017
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40243
Subject(s) - medicine , pathophysiology , fibrosis , rheumatism , rheumatology , lung fibrosis , inflammation , biomarker , gastroenterology , immunology , pulmonary fibrosis , biology , biochemistry
Objective Patients with definite systemic sclerosis ( SS c) who lack fibrotic features can be stratified into an intermediate stage of disease severity between preclinical/early SS c (Ea SS c) and fibrotic subsets (limited cutaneous SS c [lc SS c] and diffuse cutaneous SS c [dc SS c]). The aim of the present study was to molecularly characterize nonfibrotic SS c and Ea SS c on the basis of a broad panel of serum markers of inflammation and tissue damage, in order to increase the knowledge of the pathophysiologic mechanisms underlying SS c progression before the development of fibrosis. Methods An 88‐plex immunoassay was performed in serum samples from a discovery cohort composed of 21 patients with Ea SS c (meeting the LeRoy and Medsger criteria), 15 with nonfibrotic SS c (meeting the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria, without skin or lung fibrosis), and 11 healthy controls. Analyte concentrations that were consistently significantly different at the exploratory P value threshold of 0.1 were selected for replication analysis in a larger group composed of 47 patients with Ea SS c, 48 with nonfibrotic SS c, and 43 healthy controls, as well as 51 patients with lc SS c and 35 with dc SS c. The value of the replicated molecules in predicting SS c progression (at a family‐wise error rate of 0.05) was tested. Results Based on the results of the explorative analysis, 16 molecules were selected for testing in the replication set. The results showed that CXCL 10, CXCL 11, tumor necrosis factor receptor type II ( TNFRII ), and chitinase 3–like protein 1 levels were significantly increased in patients with Ea SS c and those with nonfibrotic SS c as compared to healthy controls. The disease in patients with high concentrations of CXCL 10 and TNFRII was also characterized by a faster rate of progression from Ea SS c and from nonfibrotic SS c to worse disease stages. Conclusion SS c patients with preclinical/early SS c and those with established, yet nonfibrotic, disease exhibit clear molecular alterations that are associated with faster rates of disease evolution. These data open novel avenues for disease interception in SS c.