American journal of clinical and experimental immunology最新文献

Introduction: Fingolimod is an immunomodulating oral treatment used for treating relapsing-remitting multiple sclerosis (RRMS). The exact mechanism for its action in preventing relapses is unknown. Also, its affect on immune cell populations remains unestablished.

Objectives: This study will measure the changes in cell populations of WBCs, lymphocytes, and neutrophils in MS patients after one month of treatment.

Methods: 66 MS patients from Isfahan Province with RRMS were chosen based on certain exclusion criteria and eligibility for fingolimod oral treatment. Initial cell counts for WBC, lymphocyte, and neutrophil cell populations were achieved. Fingolimod .5 mg daily treatment was then initiated under the supervision of a physician. After one month of treatment, cell counts were repeated. Statistical analysis was performed using SPSS.

Results: Both lymphocyte and WBC mean cell counts were significantly decreased in this patient cohort. Neutrophil average cell counts were significantly increased in this 66 patient cohort. Only the decrease of WBC populations was significant for both male and female cohorts individually. Only female sub-cohorts were significantly changed for neutrophils and lymphocytes, increased and decreased respectively. Male sub-cohorts maintained the same directionality but failed to produce statistical significance.

Conclusion: While fingolimod has been effectively proven as reducing lymphocyte cells in most patient populations, its effects on neutrophils have not been studied in abundance. Also, there may be sex-related differences in responses to fingolimod treatment with regards to lymphocytes and neutrophils, suggesting a possible difference in RRMS pathogenesis between males and females.

Seasonal allergic asthma prevalence has been increasing over the last decades and is one of global health concerns now. Pollen is one of the main reasons to cause seasonal allergic asthma and influenced by multiple risk factors. Thunderstorm-related asthma is a typical type of seasonal allergic asthma that thunderstorms occurring can induce severe asthma attacks during pollen season. The diagnosis of seasonal allergic asthma relies on precise medical history, skin prick tests (SPT) and specific IgE detection. Component resolved diagnosis is greatly significant in determining the complex situation. Allergen specific immunotherapy (AIT) is the only disease-modifying therapy that can change the natural course from seasonal allergic rhinitis to seasonal allergic asthma.

Background: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system, mostly affecting young adults. Diamine oxidase is an enzyme essential for histamine production. Histamine which is produced mostly by mast cells can have effects on different aspects of immune system via its different histamine receptors (H1R, H2R, H3R and H4R). The crucial role of diamine oxidase and histamine in immune balance has been documented in different studies and experiments both on MS patients and on experimental allergic encephalomyelitis (EAE). In this regard, we aimed to measure the level of histamine and diamine oxidase in the serum of MS patients.

Methods: A total number of 50 relapsing-remitting MS (RRMS) patients and 41 age and sex matched controls were enrolled in this study. Assessments of serum levels of histamine and diamine oxidase enzyme were performed using enzyme-linked immune sorbent assay (ELISA).

Results: The serum levels of histamine and diamine oxidase in RRMS patients were lower than healthy controls (P-value = 0.00, for both).

Conclusion: Our research team found significant low levels of histamine and diamine oxidase in RRMS patients; however the pathogenesis of this issue was unclear.

It was well-documented that epilepsy and pain arise from an excitation-inhibition imbalance within neuronal networks. A previous meta-analysis of data from clinical trials showed an association between anticonvulsants and specific pain types, e.g. multiple sclerosis pain. Multiple multicentre randomized controlled trials have shown that antiepileptic drugs have a prominent role in the treatment of several types of pain, e.g. neuropathic pain. Many anticonvulsants have been introduced to better manage acute postoperative pain, with improvements in analgesic efficacy and safety. These data suggested that there existed the similar mechanisms of certain forms of epilepsy and pain, and the therapeutic mechanism of spinal cord stimulation for certain forms of epilepsy and pain may be involved in the melanocortinergic signaling, and the change in cerebral glucose metabolism. We hypothesized that pressure pain assessment may predict the outcome of spinal cord stimulation in refractory epilepsy.

Multiple system atrophy is a sporadic progressive degenerative disease which is characterized by multiple central nervous systems involved. So far, there is no effective medicine to cure MSA. The main research direction of treatment includes immunization transplantation and cytotherapy. Human umbilical cord blood is the residue of blood in the placenta and umbilical cord after fetal delivery. It is the most abundant cell bank and its usage is not limited to treat hematological diseases. The researches about hUCB-MNC treatment on MSA are increasing gradually. The potential of other MSC is also discussed. Lateral atlanto-occipital space puncture is an ingenious way created by Professor Dianrong Gong. More than 30 cases of MSA have been treated by this method with fine clinical effect and without serious complications. It indicates that stem cells treatment is a valid method for refractory nerve system diseases.

Tumor cells evolve multiple sophisticated mechanisms to escape immune surveillance, one of which is to establish tolerogenic microenvironment by recruiting certain immune suppressive cells such as regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs). Tregs are subpopulation of CD4⁺ T cells, which specialize in suppressing immune responses and preventing autoimmune damage to collateral tissue. Emerging evidence suggests that Treg cell number increases in various types of cancer, which correlates with tumor grade and poor patient prognosis. This review will focus on discussion of the origins and features of tumor-infiltrating Treg cells. Ultimately, these features may provide insight into potential therapeutic intervention by targeting Treg cells to invigorate immune response against tumor.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) stimulation produces significant improvement of overall pain related to Parkinson disease; however, the mechanisms underlying analgesic effects of STN-DBS are still unknown. This report describes direct neuroanatomical evidence for the central melanocortinergic-opioidergic circuits in the STN. We investigated melanocortin-4 receptor (MC4R) and mu-opioid receptor (MOR)-positive expression of the STN in MC4R-GFP transgenic mice using fluorescence immunohistochemical detection. Immunohistochemistry showed a large number of MC4R-GFP- and MOR-positive neurons within the STN region, and approximately 50% of MC4R-GFP-positive neurons coexpressed MOR. The results of this study showed direct neuroanatomical evidence for the central melanocortinergic-opioidergic signaling in the STN region. These findings contribute to the view of melanocortinergic-opioidergic circuits in the subthalamic nucleus as a reliable source of modulating of nociception with therapeutic potential for alleviating pain.

Rationale: MicroRNAs (miRNAs) are emerging as important regulators of allergic inflammation and potential therapeutic targets. We sought to identify which miRNAs are expressed in CD4⁺ T-cells and determine whether allergic stimuli or glucocorticoids alter their expression.

Methods: After IRB approval, blood was collected from dust mite (DM) allergic rhinitis subjects (n=20), non-allergic controls (n=8), and asthmatics (n=16). Peripheral blood mononuclear cells were incubated with dust mite extract (DME), diluent control, or DME + dexamethasone (0.1 µM). CD4⁺ T-cells were collected by magnetic bead column, and RNA was isolated by guanidinium/phenol-chloroform extraction. MicroRNA expression was measured using Nanostring microarray and quantitative real time PCR (qPCR).

Results: We identified 196 miRNAs that were stably expressed in circulating CD4⁺ T-cells. Allergen stimulation of CD4⁺ T-cells with DME differentially induced miR-155 expression in cells of DM-allergic subjects as compared to non-allergic subjects. Induction of miR-155 expression was also observed with anti-CD3/anti-CD28 simulation and phorbol-12-Myristate-13-Acetate (PMA) treatment, and further augmented by calcium inophore and bromocyclic AMP in the latter treatment. The level of miR-155 expression was positively associated with expression of the T_H2 cytokines IL-5 and IL-13. Inhibition of miR-155 in Jurkat T-cells inhibited the production of these cytokines. Glucocorticoids attenuated the effects of dust mite allergen, raising the possibility that inhibition of this miRNA could be a mechanism through which glucocorticoids exhibit their anti-inflammatory effects. The CD4⁺ T-cells had a higher level of miR-155 expression in asthma compared to in allergic rhinitis and non-asthmatics. The inhibitory effects of glucocorticoids on CD4⁺ T-cell miR-155 expression were lost in severe asthmatics.

Conclusion: Mir-155 is differentially expressed in allergic T-cells exposed to DM extract compared to in non-allergic cells and it is inhibited by glucocorticoids. MiR-155 may play a role in mediating allergic inflammation in T-cells and could be an anti-inflammatory target of steroids. This pathway may be de-regulated in severe asthma.

To determine the potential changes of IL-6, IL-17A and IL-21 levels during induction therapy, and to assess their relationship with disease activity and immunologic features on patients with active lupus nephritis, twenty-eight patients treated with corticosteroid and immunosuppressants were included in this study. Demographic, clinical, serological data and disease activity were assessed. Blood samples were collected at week 0, 12 and 24, and serum concentrations of IL-17A, IL-6 and IL-21 were measured by cytometric bead array. The serum concentrations of IL-6, IL-17A and IL-21 (P<0.001, P<0.01, P=0.001, respectively) decreased progressively during induction therapy. Concentration of IL-6, IL-17A and IL-21 was higher in non-remission group than that in remission group. A positive correlation was established between the concentration of these cytokines and the severity of proteinuria (P<0.001, P=0.020, P=0.045, respectively), ESR (P<0.001), SLEDAI scores (P<0.05), and ANA titers (P=0.018, P=0.048, P<0.05, respectively). Additionally, ROC curve analysis for IL-6, IL-17A and IL-21 was performed to predict the disease activity. The optimal cutoff level was 5.78 pg/ml, 1.98 pg/ml and 8.59 pg/ml, with AUC=0.809, 0.735 and 0.786. The concentration of IL-6 and IL-21 may be regarded as an indicator for the remission of active lupus nephritis, with cutoff value of 9.12 pg/ml and 11.30 pg/ml, while AUC=0.930 and 0.896. The production of serum IL-6, IL-17A and IL-21 in active LN was dramatically declined during induction therapy, which may improve disease activity while delay disease progression of LN.

Icariin (ICA) is a major bioactive monomer belonging to flavonoid glycosides attracted from Epimedium, being a classic tonic agent in traditional Chinese medicine. ICA commonly presents multiple effects such as regulating sex hormones, relieving atherosclerosis and antioxidant activity, etc. Recently, more and more studies have demonstrated the application of ICA in autoimmune diseases such as rheumatoid arthritis, bronchial asthma, multiple sclerosis and systemic lupus erythematosus due to its anti-inflammatory. Additionally, ICA also has the anti-tumor activities. Multiple targets and mechanisms of ICA are reported which relates to regulate lymphocytes balance, anti-inflammatory/inflammatory cytokines, signal pathways like NF-kappaβ and Erk-p38-JNK, lymphocyte transcription factors and other targets such as TLRs, STAT and PTEN, etc. In this review, we have updated the advance in this field and these studies have suggested that ICA has a potential to treat immunological and inflammatory diseases.