Alterations of CD4+T Cell Subsets in Blood and Peritoneal Fluid in Different Stages of Endometriosis.

BACKGROUND: Endometriosis is a chronic inflammatory disorder with known immune disturbances. The aim of this study was to compare the frequency of different CD4+ T cells [T helper (Th)1, Th2, Th17 and regulatory T cells (Tregs)] in peripheral blood (PB) and peritoneal fluid (PF) of patients that have early and advanced stages of endometriosis with a control group. MATERIALS AND METHODS: In this case control study, PB and PF samples were collected from women aged 24-40 years who underwent laparoscopy procedures. The frequency of CD4+ T subsets were analysed by flow cytometry and compared between three study groups; early endometriosis (stage I, II), advanced endometriosis (stage III, IV) and control (no endometriosis). T cell numbers were compared between the PB and PF in each of the aforementioned groups. RESULTS: No statistically significant difference was found between the study groups regarding the numbers of Th1, Th2 and Th17 cells in PB. The PF of patients with advanced endometriosis had increased numbers of Th17 cells compared to the control group (P=0.003), with P values of 0.059 and 0.045 in both menstrual phases. Increased numbers of Th2 cells in PF from early compared to advanced stages of endometriosis were detected exclusively in the luteal phase (P=0.035). The control group had increased numbers of Treg and Th2 cells in the PF compared to PB (both, P value=0.046). However, in the early stages of endometriosis there were more Th2, Th17 and Treg cells in the PF compared to PB (P values: 0.005, 0.047 and 0.013, respectively), while the number of Th17 cells was higher in the PF compared with PB in the advanced stages of endometriosis (P= 0.013). CONCLUSION: There were increased numbers of Th17 cells in the PF of patients with advanced stages of endometriosis, which could be related to the severity of this disease.

Copy number variation of IL17RA gene and its association with the ankylosing spondylitis risk in Iranian patients: a case-control study.

BACKGROUND: Ankylosing spondylitis (AS) is considered as a subtype of spondyloarthritis (SpA) that mainly leads to fatigue, stiffness, spinal ankylosis, and impaired physical functions with reduced quality of life. Interleukin (IL)-17A provokes additional inflammatory mediators and recruits immune cells to the inflamed site. IL17 expression increased in various inflammatory disorders including psoriasis, rheumatoid arthritis, multiple sclerosis, crohn's disease, and ankylosing spondylitis. The current study aimed to evaluate the association of IL17RA copy number changes with the susceptibility to AS and their correlation to IL17RA expression in Iranian population. METHODS: IL17RA copy number genotyping assessments were carried out in 455 AS patients and 450 healthy controls, using custom TaqMan CNV assays. TaqMan primers and probe were located in Chr.22:17109553 based on pre-designed IL17RA Copy Number Assay ID, Hs02339506_cn. mRNA expression of IL17RA was also measured by SYBR Green real-time polymerase chain reaction (PCR). RESULTS: A IL17RA copy number loss (< 2) was associated with AS compared to 2 copies as reference (OR:2.18, 95% CI: (1.38-3.44), P-value < 0.001) and increased the risk of AS. IL17RA mRNA expression showed a significant increase in peripheral blood mononuclear cells (PBMCs) of all AS individuals than controls. The mRNA expression level of 2 copies was significantly higher in AS patients. CONCLUSIONS: Our findings revealed that a low copy number of IL17RA might confer a susceptibility risk to AS. However, it is probably not directly involved in the regulation of IL17RA mRNA expression. Epigenetic mechanisms like DNA methylation, post-transcriptional, and -translational modifications that regulate the expression of the genes may contribute in upregulation of IL17RA mRNA expression in the loss of gene copy number condition.

Association study between KIR polymorphisms and rheumatoid arthritis disease: an updated meta-analysis.

BACKGROUND: Currently published studies investigating association between the killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and rheumatoid arthritis (RA) reported inconsistent and contradictory results. Hence, we aim to carry out this comprehensive meta-analysis of all eligible studies meeting the inclusion criteria to achieve precise and comprehensive relationships between genetic variations in KIR gene cluster and risk of RA. METHODS: Databases of Medline/PubMed and Scopus were searched to investigate case-control studies prior to May 2018. The associations between KIR gene polymorphisms and RA susceptibility were analyzed by computing the odds ratio (OR) and 95% confidence interval (95% CI) for each study. RESULTS: A total of 11 comparative case-control studies involving 1847 RA patients and 2409 healthy individuals were included in this meta-analysis. Four significant associations of 2DL3 (OR = 0.591, 95% CI = 0.351-0.994; P = 0.047), 2DL5 (OR = 0.716, 95% CI = 0.601-0.853; P < 0.001), 2DS5 (OR = 0.623, 95% CI = 0.393-0.988; P = 0.045), and 3DL3 (OR = 0.324, 95% CI = 0.129-0.814; P = 0.016) genes with decreased RA risk were discovered in this meta-analysis. Although, other KIR receptors including 2DL1, 2DL2, 2DL4, 3DL1, 3DL2, 3DS1, 2DS1-2DS4, and two pseudo gens of 2DP1 and 3DP1 displayed no significant association with predisposition to RA. CONCLUSIONS: These findings provide reliable evidence that 2DL3, 2DL5, 3DL3, and 2DS5 might have a potential protective role for RA.

Ankylosing spondylitis and mesenchymal stromal/stem cell therapy: a new therapeutic approach.

Ankylosing spondylitis (AS) is an inflammatory rheumatoid disease categorized within spondyloarthropathies (SpA) and manifested by chronic spinal arthritis. Several innate and adaptive immune cells and secreted-mediators have been indicated to play a role in AS pathogenesis. Considering the limitations of current therapeutic approaches (NSAIDs, glucocorticoids, DMARDs and biologic drugs), finding new treatments with fewer side effects and high therapeutic potentials are required in AS. Mesenchymal stem cells (MSCs) with considerable immunomodulatory and regenerative properties could be able to attenuate the inflammatory responses and help tissue repair by cell-to-cell contact and secretion of soluble factors. Moreover, MSCs do not express HLA-DR, which renders them a favorable therapeutic choice for transplantation in immune-mediated disorders. In the present review, we describe immunopathogenesis and current treatments restrictions of AS. Afterwards, immunomodulatory properties and applications of MSCs in immune-mediated disorders, as well as recent findings of clinical trials involving mesenchymal stem cell therapy (MSCT) in ankylosing spondylitis, will be discussed in detail. Additional studies are required to investigate several features of MSCT such as cell origin, dosage, administration route and, specifically, the most suitable stage of disease for ideal intervention.

Immune cells involved in the pathogenesis of ankylosing spondylitis.

Ankylosing spondylitis (AS) is an inflammatory autoimmune disease. AS is a prototype form of spondyloarthropathies (SpA). The precise etiology of AS has not been fully understood. But Inflammation has a critical role in the pathogenesis of the disease. The immune system by various cells, secreted-mediators and markers manage and regulate the immune responses and inflammation. Every factor which disturbed this regulation and hemostasis can cause chronic inflammation. In this review, we discussed the role of several innate and adaptive immune cells involved in the triggering, initiation, development, and regulation of AS.

The relationship between infantile atopic dermatitis and urinary tract infection.

Atopic dermatitis (AD) is one of the most common infantile diseases. Immunological dysfunctions in AD patients may predispose them to infections. The aim of this study was to evaluate the relationship between infantile AD and urinary tract infection (UTI).In this cross sectional study, we enrolled 57 patients with AD aged 1 to 24 months that referred to dermatology clinic, and 57 healthy controls who were referred to pediatric clinic. The groups were matched according to age and gender. Urine samples were collected by clean-voided bag method. If a single organism was cultured at concentration of > or = 105 organisms per millimeter and the existence of white blood cells more than 10 per microscopic field was seen the patients underwent suprapubic aspiration. The presence of one organism in suprapubic aspiration sample was regarded as positive culture. Data were analyzed using SPSS version 15 software. P value <0.05 was considered as the level of significance. Twelve (21.1%) of AD patients and 1(1.8%) of normal controls had positive urine culture tests. The difference between two groups was statistically significant (p = 0.001). The most common bacteria was E-coli. Infants with AD showed a higher frequency of UTI in this study. So, we suggest screening all AD infants for urinary tract infection.