The investigation of killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands in Iranian patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a disabling disease with the underlying pathophysiology of auto-antibodies attacking the postsynaptic acetylcholine receptors of neuromuscular junctions causing muscle weakness. Natural killer (NK) cells are innate immune cells that play an important regulative role in immune responses. The human killer-cell immunoglobulin-like receptors (KIRs) family is one of the receptors on NK cells that can either activate or inhibit NK cells. This study aimed to assess the possible role of KIR and their human leukocyte antigen (HLA) ligand genes susceptibility to MG in Iranian patients. METHOD: One hundred and sixty-three patients with MG diagnosis based on the presence of clinical symptoms and laboratory tests and 400 healthy volunteers were studied. We used the polymerase chain reaction (PCR) technique for genotyping 15 KIRs and 5 HLA genes. RESULTS: The results demonstrated that there was no significant difference in the frequency of KIR genes and inhibitory KIR genotypes between controls and patients. In MG patients, HLA-C1Asn80 was significantly less frequent than in matched controls. The frequency of HLA genotype number 7 was significantly lower in MG cases, compared to the controls. Analysis of activating KIR genotypes showed that genotype number 10 was significantly less frequent in MG cases than in matched controls. CONCLUSION: Our results suggest that the presence HLA-C1Asn80 might play a protective role against the pathogenesis of MG. The significantly decreased prevalence of one activating KIR genotype and one of the HLA genotypes in MG cases suggest that these genotypes can reduce the risk of MG development. To specifically reveal the impact of KIR and HLA in MG, more studies are required.

Blood regulatory T cells in inflammatory bowel disease, a systematic review, and meta-analysis.

INTRODUCTION: Inflammatory bowel disease (IBD) is an autoimmune disease involving various parts of the gastrointestinal (GI) tract, which includes Crohn's disease (CD) and ulcerative colitis (UC). Due to the contradictory results regarding the percentage of peripheral blood (PB) regulatory T cells (Tregs) in IBD patients, this meta-analysis aimed to determine the Tregs frequency in IBD patients. METHOD: We searched PubMed, Web of Science, SCOPUS, and Google Scholar databases for relevant observational articles that analyzed and reported the frequency of PB Tregs in IBD patients and healthy control groups. After choosing the related articles by two reviewers, the data regarding the definition of Tregs and their frequencies in different groups were recorded. RESULT: In 22 studies, the results showed a nonsignificant difference in the frequency of PB Tregs between IBD cases and control subjects (SMD: -0.27, 95 % CI: -0.78, 0.23). However, the frequency of CD4+CD25+CD127- (SMD: -0.89, 95 % CI: -1.52, -0.26) and CD4+CD25+FoxP3+ (SMD: -1.32, 95 % CI: -2.37, -0.26) Tregs were significantly lower in IBD cases, compared to healthy subjects. Also, UC cases and active IBD cases showed a significantly lower frequency of Treg cells, compared to controls and remission IBD cases, respectively (SMD: -0.68, 95 % CI: -1.24, -0.11 and SMD: -0.60, 95 % CI: -0.93, -0.27). CONCLUSION: Our study highlighted a probable decrease of Tregs in IBD patients, especially the patients with active states of the disease. The decrease of Treg cells might cause an imbalance in the immune system and the over-activation of auto-immune responses against the digestive tract.

Immune checkpoint inhibitors: review of the existing evidence and challenges in breast cancer.

Cancer initiation and progression are associated with immune system responses. Tumor cells use various tricks to scape of immune system, such as activating immune checkpoint pathways that induce immunosuppressive functions. Among the different immune checkpoint receptors, CTLA-4 and PD-1/PD-L1 are prominent therapeutic targets in different cancers. Although the US FDA has approved some immune checkpoint inhibitors for several cancers, concerning breast cancer still different clinical trials are looking for optimizing efficacy and decreasing immune-related adverse events. This review will discuss the existing body of knowledge with regard to cross-talk between immune system and tumor cells and then explore immune checkpoint-related signaling pathways in the context of breast tumors. Finally, we highlight the application of different immune checkpoint blockers in breast cancer patients.

Lay abstract Breast cancer is the most commonly diagnosed female cancer around the world. Cancer initiation and progression are associated with immune system responses. Tumor cells use various tricks to scape of immune system, such as activating immune checkpoint pathways that induce immunosuppressive functions. Immune checkpoint inhibitors are drugs that help the patients' immune system with effective antitumor response. Although the US FDA has approved some immune checkpoint inhibitors for several cancers, concerning breast cancer still different examinations are looking for optimizing efficacy and decreasing immune-related adverse events. The goal of this review article is to discuss the interactions between immune system and tumor cells as well as the current state, safety and efficacy of immune checkpoint-based therapies in breast cancer treatment.