Behçet's disease (BD) is a chronic multisystemic inflammatory disorder of unknown origin consisting of oral aphthous ulcers, ocular symptoms, skin lesions, and genital ulcerations. It has many features in common with systemic vasculitides and is more prevalent in countries along the ancient Silk route. Immune-mediated mechanisms play a major role in the pathogenesis of the disease, and inflammatory mediators are also involved. BD is not considered to be an autoimmune disorder, and the character of the disease needs to be clarified. Immunological aberrations in BD have been extensively studied by many investigators; genetic factors have been related to disease susceptibility, but their exact role in the development of disease is uncertain. Environmental factors such as infectious agents have also been implicated in the etiology of BD. However, the etiopathogenesis of the disease remains to be elucidated. Factors involved in the immunopathogenesis of BD with emphasis on the role of immunological aberrations are analyzed in this review.

A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity. What is Known: • The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated. • Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis. What is New: • ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis. • ROTEM could be a useful tool in the early detection of sepsis in neonates.

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Background: The circulating levels of plasminogen activator inhibitor type 1 (PAI-1) are increased in individuals carrying the 4G allele at position -675 of the PAI-1 gene. In turn, overexpression of PAI-1 has been found to affect both atheroma and thrombosis. However, the association between PAI-1 levels and the incidence of myocardial infarction (MI) is complicated by the potentially confounding effects of well-known cardiovascular risk factors. The current study tried to investigate in parallel the association of PAI-1 activity with the PAI-1 4G/5G polymorphism, with MI, and some components of metabolic syndrome (MetS). Methods: Using meta-analytical Mendelian randomization approaches, genotype-disease and genotype-phenotype associations were modeled simultaneously. Results: According to an additive model of inheritance and the Mendelian randomization approach, the MI-related odd ratio for individuals carrying the 4G allele was 1.088 with 95% confidence interval (CI) 1.007, 1.175. Moreover, the 4G carriers had, on average, higher PAI-1 activity than 5G carriers by 1.136 units (95% CI 0.738, 1.533). The metaregression analyses showed that the levels of triglycerides (p = 0.005), cholesterol (p = 0.037) and PAI-1 (p = 0.021) in controls were associated with the MI risk conferred by the 4G carriers. Conclusions: The Mendelian randomization meta-analysis confirmed previous knowledge that the PAI-1 4G allele slightly increases the risk for MI. In addition, it supports the notion that PAI-1 activity and established cardiovascular determinants, such as cholesterol and triglyceride levels, could lie in the etiological pathway from PAI-1 4G allele to the occurrence of MI. Further research is warranted to elucidate these interactions.

Flow-cytometric analysis of peripheral blood lymphocytes was performed in 96 patients with chronic idiopathic neutropenia of adults (CINA) and in 36 age- and sex-matched healthy volunteers (controls) using a panel of monoclonal antibodies. Patients were classified arbitrarily into group A (68 patients with 2500-1500 neutrophils/microliter) and group B (28 patients with neutrophil counts below 1500/microliter). We found that CINA patients displayed low numbers of peripheral blood lymphocytes compared with the controls, which correlated with the numbers of circulating neutrophils. This decrease was due mainly to the reduction of T lymphocytes and, to lesser degree, to the decline of NK cells. Both CD4+ and CD8+ T cells decreased, so that the CD4+/CD8+ cell ratio remained within normal range. Moreover, decrease of T lymphocytes was due essentially to the diminution of CD45RO+ T-cell subsets (CD4+/CD45RO+ and CD8+/CD45RO+), while CD45RA+ T cells did not change. A highly significant positive correlation was found between the numbers of CD45RO+ T cells and the numbers of circulating neutrophils. All these alterations were more pronounced in the patients of group B than in those of group A. NK cells were found to be significantly reduced in the patients of group B, but not in those of group A. The numbers of both CD16+ and CD56+ cells correlated with the numbers of circulating neutrophils. Patients of group B had also low numbers of CD57+ cells, probably due to the reduction of T cells and NK cells. B cells did not change significantly. No significant changes were found also in the numbers of lymphocytes carrying activation-related cell surface markers. We concluded that lymphocyte reduction in CINA patients is due mainly to the diminution of CD45RO+ cells, and we postulated that the most probable explanation for this abnormality is an increased extravasation of these cells, which pass into the tissues following an accelerated adhesion to endothelial cells. This hypothesis and its relationship with the underlying neutropenia in CINA patients remain to be clarified.