Novel M. tuberculosis specific IL-2 ELISpot assay discriminates adult patients with active or latent tuberculosis

© 2018 Della Bella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Tuberculosis (TB) still is a major worldwide health problem, with 10.4 million new cases in 2016. Only 5–15% of people infected with M. tuberculosis develop TB disease while others remain latently infected (LTBI) during their lifetime. Thus, the absence of tests able to distinguish between latent infection and active tuberculosis is one of the major limits of currently available diagnostic tools. Methods A total of 215 patients were included in the study as active TB cases (n = 73), LTBI subjects (n = 88) and healthy persons (n = 54). Peripheral blood mononuclear cells (PBMCs) were isolated from each patient and the LIOSpot® TB anti-human IL-2 ELISpot assay was performed to test their proliferative response to M. tuberculosis antigens ESAT-6, CFP-10 and Ala-DH. Statistical analysis was performed to define the sensitivity and the specificity of the LIOSpot® TB kit for each antigen used and to set the best cut off value that enables discrimination between subjects with active TB or latent TB infection. Results Comparing the LIOSpot® TB results for each tested antigen between uninfected and infected subjects and between people with latent infection and active TB disease, the differences were significant for each antigen (p< 0.0001) but the ROC analysis demonstrated a high accuracy for the Ala-DH test only, with a cut off value of 12.5 SFC per million PBMCs and the Ala-DH ROC curve conferred a 96% sensitivity and 100% specificity to the test. For the ESAT-6 antigen, with a best cut off value of 71.25 SFC per million PBMCs, a sensitivity of 86% and specificity of 36% was obtained. Finally, the best cut off value for CFP-10 was 231.25 SFC per million PBMCs, with a sensitivity of 80% and a specificity of 54%. Thus, as for IGRA assays such as Quantiferon and T-Spot TB tests, ESAT-6 and CFP-10 are unable to distinguish LTBI from active TB when IL-2 is measured. On the contrary, the IL-2 production induced by Ala-DH, measured by LIOSpot® TB kit, shows high sensitivity and specificity for active TB disease. Conclusions This study demonstrates that the LIOSpot® TB test is a highly useful diagnostic tool to discriminate between latent TB infection and active tuberculosis in adults patients

Dietary Factors Modulate Helicobacter-associated Gastric Cancer in Rodent Models

Since its discovery in 1982, the global importance of Helicobacter pylori–induced disease, particularly in developing countries, remains high. The use of rodent models, particularly mice, and the unanticipated usefulness of the gerbil to study H. pylori pathogenesis have been used extensively to study the interactions of the host, the pathogen, and the environmental conditions influencing the outcome of persistent H. pylori infection. Dietary factors in humans are increasingly recognized as being important factors in modulating progression and severity of H. pylori–induced gastric cancer. Studies using rodent models to verify and help explain mechanisms whereby various dietary ingredients impact disease outcome should continue to be extremely productive.National Institutes of Health (U.S.) (P01CA028842)National Institutes of Health (U.S.) (P01CA026731)National Institutes of Health (U.S.) (P30ES002109

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients

Stromal Fibroblasts in Digestive Cancer

The normal gastrointestinal stroma consists of extra-cellular matrix and a community of stromal cells including fibroblasts, myofibroblasts, smooth muscle cells, pericytes, endothelium and inflammatory cells. α-smooth muscle actin (α-SMA) positive stromal fibroblasts, often referred to as myofibroblasts or activated fibroblasts, are critical in the development of digestive cancer and help to create an environment that is permissive of tumor growth, angiogenesis and invasion. This review focusses on the contribution of activated fibroblasts in carcinogenesis and where possible directly applies this to, and draws on examples from, gastrointestinal cancer. In particular, the review expands on the definition, types and origins of activated fibroblasts. It examines the molecular biology of stromal fibroblasts and their contribution to the peritumoral microenvironment and concludes by exploring some of the potential clinical applications of this exciting branch of cancer research. Understanding the origin and biology of activated fibroblasts will help in the development of an integrated epithelial-stromal sequence to cancer that will ultimately inform cancer pathogenesis, natural history and future therapeutics

Novel M. tuberculosis specific IL-2 ELISpot assay discriminates adult patients with active or latent tuberculosis

© 2018 Della Bella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Tuberculosis (TB) still is a major worldwide health problem, with 10.4 million new cases in 2016. Only 5–15% of people infected with M. tuberculosis develop TB disease while others remain latently infected (LTBI) during their lifetime. Thus, the absence of tests able to distinguish between latent infection and active tuberculosis is one of the major limits of currently available diagnostic tools. Methods A total of 215 patients were included in the study as active TB cases (n = 73), LTBI subjects (n = 88) and healthy persons (n = 54). Peripheral blood mononuclear cells (PBMCs) were isolated from each patient and the LIOSpot® TB anti-human IL-2 ELISpot assay was performed to test their proliferative response to M. tuberculosis antigens ESAT-6, CFP-10 and Ala-DH. Statistical analysis was performed to define the sensitivity and the specificity of the LIOSpot® TB kit for each antigen used and to set the best cut off value that enables discrimination between subjects with active TB or latent TB infection. Results Comparing the LIOSpot® TB results for each tested antigen between uninfected and infected subjects and between people with latent infection and active TB disease, the differences were significant for each antigen (p< 0.0001) but the ROC analysis demonstrated a high accuracy for the Ala-DH test only, with a cut off value of 12.5 SFC per million PBMCs and the Ala-DH ROC curve conferred a 96% sensitivity and 100% specificity to the test. For the ESAT-6 antigen, with a best cut off value of 71.25 SFC per million PBMCs, a sensitivity of 86% and specificity of 36% was obtained. Finally, the best cut off value for CFP-10 was 231.25 SFC per million PBMCs, with a sensitivity of 80% and a specificity of 54%. Thus, as for IGRA assays such as Quantiferon and T-Spot TB tests, ESAT-6 and CFP-10 are unable to distinguish LTBI from active TB when IL-2 is measured. On the contrary, the IL-2 production induced by Ala-DH, measured by LIOSpot® TB kit, shows high sensitivity and specificity for active TB disease. Conclusions This study demonstrates that the LIOSpot® TB test is a highly useful diagnostic tool to discriminate between latent TB infection and active tuberculosis in adults patients

Placental bed research: 2. Functional and immunological investigations of the placental bed

Research on the placenta as the interface between the mother and the fetus has been undertaken for some 150 years, and in 2 subsequent reviews, we attempted to summarize the situation. In the first part, we described the discovery of unique physiological modifications of the uteroplacental spiral arteries, enabling them to cope with a major increase in blood flow necessary to ensure proper growth of the fetus. These consist of an invasion of the arterial walls by trophoblast and a progressive disappearance of its normal structure. Researchers then turned to the pathophysiology of the placental bed and in particular to its maternal vascular tree. This yielded vital information for a better understanding of the so-called great obstetrical syndromes (preeclampsia, fetal growth restriction, premature labor and delivery, placenta accreta). Systematic morphological investigations of the uteroplacental vasculature showed that preeclampsia is associated with decreased or failed transformation of spiral arteries and the persistence of endothelial and smooth muscle cells in segments of their myometrial portion. Here we report on recent functional investigations of the placental bed, including in situ biophysical studies of uteroplacental blood flow and vascular resistance, and manipulation of uteroplacental perfusion. These new methodologies have provided a novel way of identifying pregnancies in which remodeling is impaired. In animals it is now possible to manipulate uteroplacental blood flow, leading to an enhancement of fetal growth; this opens the way to trials in abnormal human pregnancies. In this second part, we explored a new, extremely important area of research that deals with the role of specific subsets of leukocytes and macrophages in the placental bed. The human first-trimester decidua is rich in leukocytes called uterine natural killer cells. Both macrophages and uterine natural killer cells increase in number from the secretory endometrium to early pregnancy and play a critical role in mediating the process of spiral artery transformation by inducing initial structural changes. It seems therefore that vascular remodeling of spiral arteries is initiated independently of trophoblast invasion. Dysregulation of the immune system may lead to reproductive failure or pregnancy complications, and in this respect, recent studies have advanced our understanding of the mechanisms regulating immunological tolerance during pregnancy, with several mechanisms being proposed for the development of tolerance to the semiallogeneic fetus. In particular, these include several strategies by which the trophoblast avoids maternal recognition. Finally, an important new dimension is being explored: the likelihood that pregnancy syndromes and impaired uteroplacental vascular remodeling may be linked to future maternal and even the child's cardiovascular disease risk. The functional evidence underlying these observations will be discussed

The antigen CD300e drives T cell inflammation in adipose tissue and elicits an antibody response predictive of the insulin sensitivity recovery in obese patients

Obesity and insulin resistance (IR), the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation. Bariatric surgery leads to a considerable reduction in the adipose tissue mass and systemic inflammation along with a reduction of IR, with a whole-body metabolic improvement. However, a sizable portion of people experience an IR relapse within few years of remission. Numerous studies have attempted to explore the best clinical predictors of the improvement of insulin sensitivity and the maintenance of glucose homeostasis after bariatric surgery, but no simple fasting blood test has been found to be effective in predicting the short and long-term beneficial effects on glycaemia. With the present study, we investigated T-cell and antibody responses against CD300e, an antigen highly expressed in the adipose tissue of patients with obesity before the bariatric surgery-induced weight loss. We found both in fat tissue and in peripheral blood anti-CD300e-specific T helper 1 responses. Moreover, we evidenced in the sera of individuals with obesity an antibody response towards CD300e and revealed the existence of a significant correlation between the level of antibodies before surgery and the maintenance of glucose control after the intervention