Lower serum levels of transforming growth factor-β1 and disease activity in Takayasu arteritis

Takayasu arteritis (TAK) is a chronic inflammatory arteritis that affects large vessels (1). The inflammatory process in artery walls may persist despite the apparent control of systemic inflammation with therapy, since disease progression is observed in a significant proportion of TAK patients thought to be in remission (2). Cytokines are important players in the pathogenesis of TAK, and in vitro stimulation of peripheral blood mononuclear cells from TAK patients leads to increased Th1 and Th17 responses, whereas serum interleukin-6 (IL-6), IL-18, and B-cell activating factor (BAFF) levels best reflect disease status and disease activity in TAK (3). Increased production of Th17 response-related cytokines is ongoing in TAK patients in remission who present extensive arterial involvement or previous ischaemic events (4). Transforming growth factor-β (TGF-β) is a subfamily of cytokines with six different isoforms, but only three of them are found in mammals. TGF-β1 is the main cytokine of this subfamily and it is known by its regulatory activity and by the induction of peripheral tolerance, as it is necessary for the survival of naïve T cells and for the inhibition of the proliferation and differentiation of self-reactive T cells. The combination of TGF-β1 with IL-2 and retinoic acid promotes the differentiation of regulatory T cells (5). Conversely, TGF-β1 induces Th17 cell development in the presence of IL1β, IL-21, and IL-6 (6). The aim of this study is to evaluate TGF-β1 as a biomarker of disease status and disease activity in TAK. A cross-sectional study was performed including TAK patients who fulfilled the 1990 American College of Rheumatology classification criteria for TAK (7). Acute or chronic infectious illnesses, ongoing allergy, asthma, and a history of cancer were exclusion criteria. Sixteen consecutive TAK patients and 16 healthy controls with similar mean age (40.37 ± 13.26 years vs 38.12 ± 12.08 years, respectively, p = 0.620) and a similar frequency of females (93.8% vs 87.5%, p = 1.000) were included in the study. The study protocol was approved by the institutional ethics committee and all participants gave written informed consent. The assessment of disease activity in TAK was performed by Kerr’s criteria (8). Blood samples were collected from participants and sera were stored at −80oC with the Protease Inhibitor Cocktail Set I – Calbiochem (Merck Millipore, Burlington, MA, USA). The multiplex technique was used to determine serum levels of TGF-β1 (TGFBMAG-64k-01, Milliplex; Merck Millipore, Burlington, MA, USA) using the Luminex® 200TM System (Luminex Corporation, Austin, TX, USA), according to the manufacturer’s instructions. Statistical analysis was carried out with SPSS Statistics forWindows version 20.0 (IBMCorp., Armonk,NY,USA) and GraphPad Prism version 6.00 for Windows (GraphPad Software, La Jolla, CA, USA). Comparisons between groups were performed by the Student’s t-test or by oneway analysis of variance, with Dunnett’s tests for post-hoc analysis. Correlations were assessed by Spearman’s test. Table 1 describes the characteristics of the TAK patients. Six TAK patients (37.5%) presented active disease. Eight TAK patients (50.0%) were under therapy with an