American journal of clinical and experimental immunology最新文献

Macrophages play critical roles in inflammatory initiation, development, resolution and cardiac regeneration of myocarditis. However, Reg3β, as a member of regenerating family of proteins, contributes to dedifferentiation of injury cardiomyocytes as well as cardiac function remodeling. It remains unclear whether Reg3β was associated with macrophages reprogramming during autoimmune myocarditis. Our results showed that Reg3β could effectively recruit macrophages, promoted their proliferation and phagocytosis, and facilitated their polarized into M2 macrophages. Macrophage, especially M1 phenotype contributed to Reg3β production by cardiomyocytes. Our data also indicated that Reg3β was involved in self-protection mechanism following cardiac injury or stress. This suggests that Reg3β might be a critically protective factor of myocardium.

To investigate autonomic substrates of brainstem-gut circuitry identified using trans-synaptic tracing with pseudorabies virus (PRV)-152, a strain that expresses enhanced green fluorescent protein, and PRV-614, a strain that expresses enhanced red fluorescent protein, injecting into the rat rectum wall. 3-7 days after PRV-152 injection, spinal cord and brainstem were removed and sectioned, and processed for PRV-152 visualization using immunofluorescence labeling against PRV-152. 6 days after PRV-614 injection, brainstem was sectioned and the neurochemical phenotype of PRV-614-positive neurons was identified using double immunocytochemical labeling against PRV-614 and TPH. We observed that the largest number of PRV-152- or PRV-614-positive neurons was located in the gigantocellular reticular nucleus (Gi), lateral paragigantocellular (LPGi), rostral ventrolateral reticular nucleus (RVL), solitary tract nucleus (Sol), locus coeruleus (LC), raphe magnus nucleus (RMg), subcoeruleus nucleus (SubCD). Double-labeled PRV-614/tryptophan hydroxylase (TPH) neurons were concentrated in the RMg, LPGi and Sol. These brainstem neurons are candidates for relaying autonomic command signals to the gut. The autonomic substrate of brainstem-gut circuitry likely plays an important role in mediating different aspects of stress behaviors.

Objective: The aim of this study was to investigate the associations between HSP90B1 gene polymorphisms and the efficacy of glucocorticoids (GCs) and the improvement of health-related quality of life (HRQoL) in Anhui patients with systemic lupus erythematosus (SLE). Method: A total of 305 patients with SLE were recruited to the study. These patients were treated with GCs for 12 weeks and classified into two groups (sensitivity and insensitivity) according to the response to GCs measured by the scores on SLE disease activity index (SLEDAI). The HRQoL of SLE patients were evaluated by 36-item Short Form Health Survey (SF-36) at baseline and 12 weeks respectively. HapMap database and Haploview software were used to select HSP90B1 gene tag single nucleotide polymorphisms (SNPs). Benjamini & Hochberg (BH) method based on false discovery rate (FDR) was used for multiple testing correction. Results: A total of 291 patients were included in final data analysis with 14 patients excluded due to loss to follow-up. Among these patients, 160 patients were sensitive to GCs and 131 patients were insensitive to GCs. Twelve tag SNPs of HSP90B1 gene were selected. The rs12426382 polymorphism was associated with the efficacy of GCs (dominant model: crude OR=0.514, 95% CI=0.321-0.824, P=0.006; adjusted OR=0.513, 95% CI=0.317-0.831, P=0.007). After BH correction, there was no association between rs12426382 polymorphism and efficacy of GCs (P_BH =0.084). In haplotype analysis, the haplotype CCCGAACATCCC (OR=2.273, 95% CI=1.248-4.139, P=0.006) and CTGGGACGTTC (OR=0.436, 95% CI=0.208-0.916, P=0.025) showed significant associations with the efficacy of GCs. After corrected by BH method, CCCGAACATCCC was still associated with the efficacy of GCs (P_BH =0.048). The rs3794241, rs1165681, rs2722188, rs3794240 and rs10861147 polymorphisms were associated with the improvement of HRQoL among SLE patients (P < 0.05). But no association existed after the correction of BH method (P > 0.05). Conclusions: The results of this study demonstrated that HSP90B1 genetic polymorphisms might be associated with the efficacy of GCs, but not associated with the improvement of HRQoL in Anhui population with SLE.

Osteoporosis (OP) and osteoporotic fractures are becoming a serious health care issue in the world. Calcium and vitamin D are the basic treatment for osteoporosis. Nonetheless, they do not effectively reduce the incidences of fracture. Currently approved treatments for osteoporosis include selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab, teriparatide, calcitonin and others. However, the appearance of some adverse effects including atypical fracture and breast cancer has limited long-term treatments above mentioned. Therefore, treatment decision should be made on an individual basis, taking into account the relative benefits and risks in different patients. Bone metabolism test helps to assess the patient's condition, which may ultimately lead to therapeutic options and better clinical outcomes.

Posterior reversible encephalopathy syndrome (PRES) is a rare clinical entity associated with systemic lupus erythematosus which characterized by seizure, headache, and altered mental status. The pathophysiology involves subcortical vasogenic edema secondary to hypertension and endothelial damage. PRES is reversible with withdrawal of the offending agent, strict blood pressure control, and treating the underlying disease. We report present here a patient with lupus nephritis who developed PRES following mycophenolate administration.

The Background: Diacerein has been proposed as a treatment option for management of type 2 diabetes due to its anti-inflammatory properties.

Purpose: The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to examine the effect and safety of diacerein in patients with type 2 diabetes.

Data sources and study selection: We searched Pubmed, Embase, and Cochrane Library for RCTs published from database inception to September 2017.

Data extraction and data synthesis: Among 44 studies that were initially identified, four were eligible and were included in the following analysis. Diacerein significantly reduced fasting glycemia [weighted mean differences (WMD) -0.66, 95% confidence interval (95% CI) -1.16 to -0.16] and glycated hemoglobin A1c (HbA1c ) (WMD -0.85, 95% CI -1.44 to -0.26). And the patients with a diacerein supplementation duration of ≤12 weeks had a greater decrease of fasting glycemia and HbA1c than the supplementation duration of >12 weeks. Furthermore, compared with placebo, diacerein revealed a significant increase in the relative risk (RR) of gastrointestinal symptoms (RR=2.50, 95% CI: 1.10 to 5.65), especially in the study subgroup with supplementation duration of >12 weeks (RR=4.01, 95% CI: 2.32 to 6.95).

Limitations: The sample size was relatively small and the duration of included studies was short so that the treatment efficacy and safety for longer duration was unknown.

Conclusions: Although further studies are needed, our findings clearly provide support to the use of diacerein in the clinical management of subjects with type 2 diabetes.

A joint function of tissues, organs and cells for the protection of body develops immune system. The human immune response against various infections during sleep, its mechanism, neuroimmune interactions, immunoregulatory effect of sleep along with sleep deprivation and role of cytokines in sleep deprivation were addressed. It is revealed that human immune system and sleep both are associated and influenced by each other. Sleep deprivation makes a living body susceptible to many infectious agents. In the result, immune system of human body is altered by releasing immunomodulators in the response of infections as reported by various researchers. Basic reasons and mechanisms of most of the poor sleep networks and release of proinflammatory modulators are still uncertain. The current situation requires improved sleep habits to make immune system efficient for a healthy life.

Background: Giant cell arteritis (GCA) is a chronic vasculitis of large and medium vessels in which no targetable biomarkers exist to allow selective treatment, predict disease activity and monitor therapeutic responses. The accessibility of the temporal artery (TA) for biopsy allows morphologic studies to characterize macrophages and T cells in the microenvironment of the arterial wall. We evaluated the expression of folate receptor beta (FRB), a candidate diagnostic/therapeutic biomarker, compared its expression with key macrophage markers and correlated it with GCA severity.

Methods: Formalin-fixed paraffin-embedded tissue sections were examined from 6 patients with GCA and 2 controls. Immunohistochemistry was performed using FRB, ETB, CD68 and CD3 antibodies to evaluate for activated macrophages and T cells, assess FRB distribution along the intima, media and adventitial layers and composition of inflammatory infiltrates. We compared the expression of FRB, ETB and CD68 in GCA versus negative controls and in severe (with visual loss) versus mild (without visual loss) disease.

Results: In GCA, moderate to severe inflammation was accompanied by >90% destruction of the internal elastic lamina. Macrophages comprised 36.3 ± 4.1% while CD3+ lymphocytes accounted for 61.7 ± 4.1% of total leukocytes. FRB was selectively expressed in macrophages and localized to the adventitia. GCA patients had marginally increased median FRB (9.8 cells/hpf vs. 0; p=0.095), ETB (20.5 vs. 0; p=0.095) and CD68 (38.8 vs. 5; p=0.071) expression versus controls. ETB was found in endothelial cells, smooth muscle cells and macrophages in intima/media. FRB positively correlated with ETB (r=0.90; p-0.037) and CD68 levels (r=0.90; p=0.037). ETB expression positively correlated with CD68 (r=1.0; p<0.0001). There was no difference in FRB between severe and mild GCA.

Conclusion: FRB is a potential diagnostic and therapeutic biomarker with restricted expression in GCA macrophages. FRB+ macrophages localized to the adventitia and their expression correlated with ETB and CD68 macrophages, suggesting that they contribute to GCA pathogenesis.

Immunoglobulin replacement therapy (IRT) is standard treatment for patients with primary immunodeficiency (PID). Because most of the patients with PID will require long life-time immunoglobulin replacement therapy, the quality of the prescribed products is of utmost importance. The IRT is generally administered either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG). Both routes have been demonstrated to be effective. The preferred route may vary at different times during a given patient's life. Options are therefore not fixed and the choice of route for immunoglobulin therapy will depend on several factors, including patient characteristics, clinical indication, venous access, side effects, rural or remote location, treatment compliance and patient preference. Many years ago, immunoglobulin therapy was associated with side effects which may compromise patient's compliance and quality of life of the patients. Most of the side effects were related to impurities. Recently, major advances in the manufacturing process have been made and new processes, such as the Quality by design (QbD) approach were added into the manufacturing steps to ensure patients tolerability and safety. Due to the improved purity of the immunoglobulin products obtained by these processes, the incidence of side effects is lower, while the ways of administration of Ig therapy and the choice of the regimen has widened to suit patient's preference and needs.

Autoantibody (autoAb) response is an important arm of endogenously arising anti-tumor immune responses, and has received new attention as a cancer biomarker with the recent success of immune check-point inhibitor therapy. Our laboratory has been focusing on measuring autoAb against B-cell epitopes in order to bypass the necessity to purify a panel of recombinant proteins. In order to optimize peptide-based autoAb measurement and to increase sensitivities to cover more patients, we developed a new approach of using mixed peptides to conjugate on the same microsphere and compared its results with the use of a dominant peptide epitope using Luminex microbead-based multiplex assays. The peptide epitopes of two cancer/germline antigens, New York esophageal cancer antigen-1 (NY-ESO-1) and X antigen family member-1b (XAGE-1b), and cancer/stem cell antigen, sex determining region Y-box-2 (SOX2), were used as prototypes in this study. Our results indicate that using mixed peptides of B-cell epitopes improves the sensitivity of detecting more patients with autoAb responses. Thus, when the full-length protein is not available for conjugating onto microspheres, a mixture of B-cell epitopes is the method of choice for using Luminex multiplex assay to detect autoAb response in cancer patients.