Summary Multifactorial mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) might condition the ability of patients with ITP to respond to treatments. Examining their platelet and immune features, we aimed to detect singular characteristics of patients with ITP who do not respond to any treatment. We studied patients with chronic primary ITP who had been without treatment, or untreated (UT‐ITP), for at least six months; included were responders to agonists of thrombopoietin receptors (TPO‐RA), patients who showed no response to first‐ and second‐line treatments (NR‐ITP), and healthy controls. Platelets from NR‐ITP patients exposed a reduced amount of sialic acid residues. Increased loss of platelet surface sialic acid residues was associated with increased platelet apoptosis. NR‐ITP patients had an increased fraction of naive lymphocyte (L) B cells and a reduced LTreg (Lymphocyte T‐regulator) subset. They also presented an anomalous monocyte and NK (Natural Killer) cells distribution. TPO‐RA‐treated patients seemed to recover an immune homeostasis similar to healthy controls. In conclusion, our results indicate a severe deregulation of the immune system of NR‐ITP. The inverse correlation between loss of sialic acid and LTreg count suggests a potential relationship between glycan composition on the platelet surface and immune response, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP.

Our data demonstrates the presence of functional T(Reg) cytotoxic properties in biological systems and support the concept that E2 enhances the number and function of T(Reg) suggesting the potential interaction between E2 and immunoregulatory mechanisms.

Multiple sclerosis (MS) represents the leading cause of neurological deficit among young adults, affecting women more frequently than men. In MS, the extent of central nervous system lesions is determined by the net balance between self-reactive and regulatory T-cells at any given time, among other factors, as well as by the effect of inflammatory response. Here, we studied both CD4+ and CD8+ TReg in parallel in blood and CSF during MS relapse. A recruitment of both regulatory CD4+ and CD8+ T cells (TReg) within the cerebrospinal fluid (CSF) takes place during MS relapse. Not previously described, the presence of CD4+ TReg in CSF was higher in women than in men, which could account for the sexual dimorphism in the incidence of MS. A direct correlation between plasma oestradiol (E2) and IL-2 levels was observed, in line with a putative circuit of E2 and perforin expression by CD4+ TReg playing a role in MS. Also, serum IFN-alpha was higher in females, with direct correlation with serum E2 levels. This is the first study to analyze perforin expression by CD4+ TReg in MS, which was greatly enhanced in CSF, what points out a relevant role of this molecule in the suppressive effects of the CD4+ TReg in MS, and contributes to the understanding of MS pathophysiology.

Objective:The aims of this study were to describe the long-term retention rate of golimumab (GLM) treatment in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA) in real life, and to analyze determinants of discontinuation. Methods:We conducted a single-center, medical records review study of all patients with RA, PsA, and SpA on GLM treatment attending a large rheumatology department from 2010 to 2017. Times from start to end of GLM treatment were collected, as well as sociodemographic, clinical, and safety variables. Golimumab retention rate was estimated by the Kaplan-Meier method, and comparison across diseases was analyzed with the Mantel-Haenszel statistic (log-rank test). Cox proportional hazards regression models were used to identify factors associated with GLM discontinuation.Results: In the study period, a total of 212 patients (61 RA, 48 PsA, 103 SpA) were prescribed GLM. Retention rates were 72% in the first year, 61% in the second, 56% in the third, and 38% at 5 years. Differences were statistically significant across diseases (median times to GLM discontinuation were 50.2, 46.0, and 38.7 months for RA, SpA, and PsA, respectively) and according to the number of previous biologic therapies (55.2 months in biologic-naive patients vs 14.0 months in patients with ≥2 previous biologics; p < 0.001). The use of concomitant conventional synthetic disease-modifying antirheumatic drugs was associated with a lower probability of discontinuation (hazards ratio [HR], 0.57; 95% confidence interval [CI], 0.33-0.97). Female sex (HR, 1.84; 95% CI, 1.07-3.17) and having used 2 biologics before GLM (HR, 2.99; 95% CI, 1.76-5.06) were associated with increased discontinuation rates. Twenty-three patients (10.9%) had at least 1 serious adverse event.Conclusions: In a real-life setting, GLM shows appropriate long-term safety-effectiveness ratio.