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Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients. [ABSTRACT FROM AUTHOR]

Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon-gamma (IFN-γ)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months'(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-β1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively. In Fingolimod treated MS patients, we observed a significant decrease in the percentage of IFN-γ+/IL17+ CD4+ and CD8+ T cell subsets. In contrast, Fingolimod increased IL10+ CD4+ T cells. We also showed that IFN-γ+IL17+ co-producing CD8+ T cells were reduced in patients under fingolimod therapy. furthermore, Fingolimod could reduce the expression level of IRF4 in patients while IL6 was increased in the supernatant of cultured peripheral blood mononuclear cells. Our data showed that Fingolimod treatment alters CD4+ and CD8+ T cell subsets and reduces expression of IRF-4, which affects the proportion of pathogenic memory T cells in peripheral blood. [ABSTRACT FROM AUTHOR]

Background: Chronic Rhinosinusitis (CRS) is a persistent inflammatory disease affecting paranasal sinuses. CRS is categorized into two distinct subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Although several immune cells are involved in the CRS pathogenesis, the role of T cells is not fully understood. The objective of the present study was to evaluate the frequency of CD4+ and CD8+ T cells and macrophages in the sinonasal mucosa of CRS patients, as well as to investigate the specific transcription factors for Th1, Th2, Th17, and Treg cells. Methods: In this study, 15 healthy controls, 12 CRSsNP, and 23 CRSwNP patients participated. CD4+, CD8+, and CD68+ cells were investigated in the sinonasal tissues using immunohistochemistry. The expression of transcription factors related to Th subsets (T-bet, GATA3, Ror-γt, and FoxP3) was evaluated using real-time PCR. Furthermore, CRSwNP patients were defined as eosinophilic when eosinophils consisted of more than 10% of total inflammatory cells. The Kruskal–Wallis, Mann–Whitney, and Spearman tests were used in statistical analyses. Results: The median (range) age of the studied groups was: 32 (14–67) for CRSwNP, 28 (10–43) for CRSsNP, and 27 (17–44) for controls. The number of eosinophils in CRSwNP patients was higher than two other groups, whereas neutrophils were elevated in both CRSwNP and CRSsNP groups in comparison to controls. The frequency of CD4+ and CD8+ T cells, macrophages, and total inflammatory cells were significantly increased in CRSwNP and CRSsNP patients compared with controls. The mRNA expression of GATA3 was increased in CRSwNP patients while mRNA expression of Ror-γt was elevated in CRSsNP patients. No significant difference was observed in T-bet mRNA expression among three groups. Both CRSwNP and CRSsNP patients showed decreased FoxP3 mRNA expression in comparison to controls. Conclusion: The frequency of CD4+ and CD8+ T cells was elevated in CRS patients. In addition, we demonstrated Th2 dominance in CRSwNP patients and Th17 dominance in CRSsNP patients, implicating different mechanisms may underlie the disease. Better CRS classification and targeted therapeutic strategies may be achievable by determining the pattern of infiltrating inflammatory cells. Therefore, further experimental investigations on T cells are needed. [ABSTRACT FROM AUTHOR]

• Increased naïve T-cells in the CD4 T-lymphocyte population. • Increased TEMRA (effector memory T-cells that re-express CD45RA) cells in the CD8 T-cell population. • Treg:Tcons and Treg:CD8 ratios in patients with chronic G v HD. • Impaired reconstitution of distinct CD4 and CD8 T-cell subsets and their imbalance with Tregs may be involved in developing acute and chronic G v HD. The reconstitution of different T-cell subsets following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is critical for efficient pathogen protection and the prevention of graft-versus-host disease (G v HD). In particular, studies have highlighted the importance of balanced ratios of regulatory T-cells (Tregs) and distinct functionally T-cells in preventing acute and chronic G v HD. We evaluated the regeneration of CD4 and CD8 T-cell subpopulations in nine pediatric patients with non-malignant disorders following allo-HSCT from a fully HLA-identical donor. CD4 and CD8 T-cells were higher 12 months after the transplant but still lower than in healthy controls and pre-transplant. However, we found after allo-HSCT, central memory and effector memory cell subsets were the predominant phenotypes in the CD4 and CD8 T-cell populations, respectively. In patients who had developed acute G v HD, there was an increase in the frequency of TEMRA (effector memory T cells that re-express CD45RA) cells within the CD4 T-cell population. Meanwhile, in patients with chronic G v HD, we observed a decrease in Th1 cells in CD4 T-cells and effector memory cells within the CD8 T-cell population. In addition, we found decreased TEMRA cell subsets in CD4 and CD8 T-cell populations in chronic G v HD. Our findings suggest a possible relationship between the influence of acute G v HD and its prevention on delayed CD4 T-cell reconstitution and, reciprocally, unbalanced regeneration of CD4 and CD8 T-cell subsets in the development of chronic G v HD. [ABSTRACT FROM AUTHOR]

Autophagy is considered as an important intracellular mechanism that degrades cytoplasmic components to furnish additional energy. It has cytoprotective effects through the degradation of intracellular pathogens, damaged organelles, and protein aggregates. On the other hand, there are reports of an association between autophagy and autoimmune diseases. Indeed, it has been evident that autophagy is dysregulated in various autoimmune diseases including rheumatoid arthritis (RA). Autophagy is implicated in the maturation survival and proliferation of various immune and non-immune cells, which play pivotal roles in RA pathogenesis. Additionally, autophagy seems to be involved in citrullination and presentation of citrullinated peptides to T lymphocyte cells. Presentation of citrullinated peptides through MHC compartments to the T cells leads to immune response and chronic inflammation. Evidence suggests that autophagy could be implicated in apoptosis resistance of RA fibroblast-like synoviocyte (RA FLS), osteoclastogenesis, and finally severe bone and cartilage destruction. Since autophagy could be an important phenomenon in RA pathogenesis, we summarized the roles of autophagy in citrullination, osteoclastogenesis, RA FLS cells survival, apoptosis resistance of cells, lymphocyte homeostasis and its clinical outcomes in RA disease. Unlabelled Image [ABSTRACT FROM AUTHOR]