Serum calprotectin correlated significantly with CRP and ASDAS-CRP but not with the frequency of circulating CD19+CD24hiCD38hi B cells (Fig 2C)

Serum calprotectin correlated significantly with CRP and ASDAS-CRP but not with the frequency of circulating CD19+CD24hiCD38hi B cells (Fig 2C). Open in a separate window Fig 2 The frequency of circulating CD19+CD24hiCD38hi B cells in AS/nb patients is not related with disease activity scores and/or inflammatory serological markers.A. Breg-depleted CD19+ B cells were established in culture and stimulated through their BCR. Secretion of IFN was determined by ELISA in culture supernatants. When compared with HC, AS/nb patients demonstrated a significantly increased frequency of Breg cells, which was independent of disease activity. Anti-TNF drugs induced a significant reduction of ABT 492 meglumine (Delafloxacin meglumine) circulating Breg numbers, which were no longer elevated after six months of treatment. Functional in vitro studies showed that the secretion of IFN was significantly higher in Breg-depleted as compared with total CD19+ B cells, DIAPH2 indicating that Breg can downmodulate B cell pro-inflammatory cytokine secretion. In summary, an increased frequency of circulating CD19+CD24hiCD38hi B cells is observed in AS/nb patients, that is not related with disease activity; anti-TNF drugs are able to downmodulate circulating Breg numbers in AS. Introduction The pathogenesis of Ankylosing spondylitis (AS), the prototype form of Spondyloarthritis (SpA), is not well understood, and evidence indicating a role for either autoinflammatory or autoimmune mechanisms has been described [1]. An interesting report by Cantaert et al [2] has shown an increased number of IL-10 producing CD19+CD5+ B lymphocytes in SpA. B cells are not merely a source of antibodies [3]; they also act as very efficient antigen presenting cells and as cytokine producers [3]. In addition regulatory B cells, a subspecialized B cell subset, contribute to the maintenance of peripheral tolerance by downmodulating T and B cell function [4,5]. Phenotypical characterization of Bregs in mice or humans is not straightforward, and different definitions of Bregs have been proposed based on distinct cell surface markers [6]; however, Bregs have not been demonstrated to constitute a unique cell lineage [6]. Therefore, IL-10 production together with functional inhibition of T or B cell responses remain the gold standard for Breg definition [6]. In human peripheral blood, immature CD19+CD24hiCD38hi B cells contain a high proportion of IL-10 producing cells [7,8] and functionally behave as suppressors of Th1 responses and Th17 differentiation [9]. In addition, CD19+CD24hiCD38hi B cells are able to induce Treg and Tr1 phenotype from CD4+ T cells [9]. Patients with autoimmune conditions such as systemic lupus erythematosus (SLE) [7], RA [9], primary Sj?grens syndrome [10], ANCA-associated vasculitis [11], and Systemic Sclerosis [12,13], have been shown to demonstrate altered numbers and/or function of circulating CD19+CD24hiCD38hi B cells. In addition, whereas Cantaert et al described an increased number of circulating CD19+CD5+ B cells with a regulatory phenotype in SpA [2], Chen et al reported normal numbers of CD19+CD24+CD38+ B cells with decreased IL-10 production in AS patients [14]. To our knowledge, these are the two only published reports on the numbers of circulating B cells with regulatory properties in SpA. Therefore, our objective was to investigate on the frequency of ABT 492 meglumine (Delafloxacin meglumine) circulating CD19+CD24hiCD38hi B cells in AS and test the regulatory capacity of this B cell subset. Patients and methods Ethics statement The study was approved by the Hospital La PazIdiPAZ Ethics Committee (protocol number ABT 492 meglumine (Delafloxacin meglumine) HULP PI-883), and all subjects provided written informed consent according to the Declaration of Helsinki. Patients Peripheral blood was obtained from 42 AS patients who had never received TNF blockers (AS/nb) (Table 1 and S1 Table) and from 42 age and gender-matched healthy controls (HC) (S2 Table). All subjects were studied between the years 2014 and 2016. Patients were recruited among those attending the outpatient Rheumatology Clinic at Hospital Universitario La Paz (Madrid, Spain). Inclusion criteria for patients were age greater than 18 years and AS diagnosis according to the 1984 modified New York criteria [15], exclusion criteria were a history of previous treatment with biological agents and infection with HBV, HCV or HIV. Healthy controls were recruited among hospital and laboratory workers. Inclusion criteria for controls were age greater than 18 years; exclusion criteria for controls were current or chronic medication intake, the current presence of any known disease an infection or condition with HBV, HCV or HIV. Forty-seven sufferers were contacted and 42 recognized to take part; fifty controls had been contacted and 42 recognized to participate. There have been no dropouts. Among sufferers, 28 were acquiring nonsteroidal anti-inflammatory medications (NSAIDs), 7 had been getting sulfasalazine (SSZ); 3 methotrexate (MTX) and 7 of these did not consider any medication frequently. 31 sufferers had a 100 % pure axial disease (13 feminine, 18 male) and 11 sufferers (4 feminine, 7 male) acquired a combined mix of axial and peripheral manifestations (Desk 1 and S1 Desk). All topics were of EUROPEAN descent. Desk.