NK-b

Spondyloepimetaphyseal dysplasia (SEMD) is a group of genetic skeletal disorders characterized by disproportionate short stature, and varying degrees of vertebral, epiphyseal, and metaphyseal involvement of the skeleton. According to the Nosology and classification of genetic skeletal disorders 2019 revision, more than 20 types of SEMD have been identified, and SEMD with immune deficiency, EXTL3 type is one of the newcomers. Affected individuals display variable skeletal abnormalities and neurodevelopmental findings...

OBJECTIVE: The gut microbiome plays an important role in systemic inflammation and immune response. Microbes can translocate and reside in tumour niches. However, it is unclear how the intratumour microbiome affects immunity in human cancer. The purpose of this study was to investigate the association between intratumour bacteria, infiltrating CD8+ T cells and patient survival in cutaneous melanoma. METHODS: Using The Cancer Genome Altas's cutaneous melanoma RNA sequencing data, levels of intratumour bacteria and infiltrating CD8+ T cells were determined...

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients manifest with pulmonary symptoms reflected by diffuse alveolar damage (DAD), excessive inflammation, and thromboembolism. The mechanisms mediating these processes remain unclear. METHODS: We performed multicolor staining for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and lineage markers to define viral tropism and lung pathobiology in 5 autopsy cases. RESULTS: Lung parenchyma showed severe DAD with thromboemboli...

BACKGROUND: Inflammatory bowel disease (IBD) is a complex disease with variable presentation, progression, and response to therapies. Current disease classification is based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, and thus we measured 39 circulating immune cell types in a large cohort of IBD and control subjects and performed immunotype:phenotype associations. METHODS: We performed fluorescence-activated cell sorting or CyTOF analysis on blood from 728 Crohn's disease, 464 ulcerative colitis, and 334 non-IBD patients, with available demographics, endoscopic and clinical examinations and medication use...

COVID-19 is a life-threatening disease leading to bilateral pneumonia and respiratory failure. The underlying reasons why a smaller percentage of patients present with severe pulmonary symptoms whereas the majority is only mildly affected are to date not well understood. Comparing the immunological phenotype in healthy donors and patients with mild versus severe COVID-19 shows that in COVID-19 patients, NK/B cell activation and proliferation are enhanced independent of severity. As an important precondition for effective antibody responses, T follicular helper cells and antibody secreting cells are increased both in patients with mild and severe SARS-CoV-2 infection...

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) can in rare cases occur in natalizumab-treated patients with high serum anti-JCPyV antibodies, hypothetically due to excessive blockade of immune cell migration. OBJECTIVE: Immune cell recruitment to the central nervous system (CNS) was assessed in relapsing-remitting multiple sclerosis (RRMS) patients stratified by low versus high anti-JCPyV antibody titers as indicator for PML risk. METHODS: Cerebrospinal fluid (CSF) cell counts of 145 RRMS patients were quantified by flow cytometry...

Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild ( n = 22), moderate ( n = 25), and severe ( n = 8) according to the Guidelines released by the National Health Commission of China...

Near infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that employs a monoclonal antibody (mAb) conjugated to a photo-absorber dye, IRDye700DX, which is activated by 690 nm light. Cancer cell-targeted NIR-PIT induces rapid necrotic/immunogenic cell death (ICD) that induces antitumor host immunity including re-priming and proliferation of T cells. Interleukin-15 (IL-15) is a cytokine that activates natural killer (NK)-, B- and T-cells while having minimal effect on regulatory T cells (Tregs) that lack the IL-15 receptor...

A novel member of human coronavirus, named SARS-CoV-2, has been recently recognized in China and rapidly spread worldwide. Studies showed the decreasing of peripheral blood lymphocytes in a majority of patients. In this study, we have reported the clinical features, laboratory characteristics, the frequency of peripheral blood lymphocyte subpopulations and their apoptosis pattern in Iranian COVID-19 patients. Demographic and clinical data of 61 hospitalized confirmed cases with COVID-19 at Imam Khomeini Hospital were collected and analyzed...

MYC is implicated in the development and progression of pancreatic cancer, yet the precise level of MYC deregulation required to contribute to tumor development has been difficult to define. We used modestly elevated expression of human MYC, driven from the Rosa26 locus, to investigate the pancreatic phenotypes arising in mice from an approximation of MYC trisomy. We show that this level of MYC alone suffices to drive pancreatic neuroendocrine tumors, and to accelerate progression of KRAS-initiated precursor lesions to metastatic pancreatic ductal adenocarcinoma (PDAC)...

PURPOSE OF REVIEW: Hyperexpression of classical HLA class I (HLA-I) molecules in insulin-containing islets has become a widely accepted hallmark of type 1 diabetes pathology. In comparison, relatively little is known about the expression, function and role of non-classical subtypes of HLA-I. This review focuses on the current understanding of the non-classical HLA-I subtypes: HLA-E, HLA-F and HLA-G, within and outside the field of type 1 diabetes, and considers the possible impacts of these molecules on disease etiology...

BACKGROUND: Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency disorders that is characterized by impaired early T lymphocyte differentiation and is variably associated with abnormal development of other lymphocyte lineages. SCID can be caused by mutations in more than 20 different genes. Molecular diagnosis in SCID patients contributes to genetic counseling, prenatal diagnosis, treatment modalities, and overall prognosis. In this cohort, the clinical, laboratory and genetic data related to Iranian SCID patients were comprehensively evaluated and efficiency of stepwise sequencing methods approach based on immunophenotype grouping was investigated METHODS: Clinical and laboratory data from 242 patients with SCID phenotype were evaluated...

Prominent dermal infiltration by Langerhans cells (LC) is a rare finding in patients with Omenn syndrome (OS). Here, we report the case study of a 7-month-old boy with OS and with prominent dermal infiltration by LC, which is a rare histological manifestation of the skin. Striking erythroderma appeared in the patient 2 weeks after birth. We also noted alopecia, lymphadenopathy, hepatosplenomegaly, eosinophilia and an elevated serum immunoglobulin E level with hypogammaglobulinemia. Peripheral blood flow cytometry showed the Tlow NK+ B+ immunophenotype and genetic analysis, a novel mutation in the IL2RG gene (c...

We previously reported that deletion of Foxo1, via Ncr1 -iCre mice from the expression of NKp46 onward, led to enhanced natural killer (NK) cell maturation and effector function. In this model, however, the role of Foxo1 in regulating NK cell specification and early development remains exclusive. Herein, we utilized a murine model of hematopoietic-specific deletion of Foxo1 before lymphoid specification, by crossing mice carrying floxed Foxo1 alleles ( Foxo1 fl/fl ) with Vav1 -iCre mice, to revisit the role of Foxo1 on NK cell specification and early development...

A tumor consists of a group of cells with abnormal growth, capable of acquiring unique characteristics that provide them with the ability to display mercurial migration patterns, adapting to microenvironments and their chemical and physical factors. Interleukins are small proteins secreted mainly by CD3+ and CD4+ T lymphocytes that mediate the "essential for cancer progression" interactions between cells. Interleukins are implicated in both the development and differentiation of different cells (NK, B, and T leukocytes) and, in general, play a major role in many diseases, including breast cancer, due to their unique participation in systemic inflammation and immune system modulation...

Major histocompatibility complex (MHC) class II deficiency is a rare primary immunodeficiency disorder (PID) with less than 200 cases worldwide. Here, we report an 8 month-old girl with MHC class II deficiency with a novel homozygous mutation in RFXANK gene (NM_001278728: exon 5: c.495G>A: p.Trp165*) and normal CD4+ T cell counts, diagnosed by whole exome sequencing (WES) and negative HLA-DR proteins on peripheral blood mononuclear cell (PBMC) in flow cytometry. She was referred with pneumonia, prolonged fever, resistance to antibiotics (ceftriaxone, clindamycin, and vancomycin), and low serum immunoglobulin (IG) levels, while natural killer (NK), B, and T cells were normal...

We are studying the fully human, IgG1λ cytolytic monoclonal antibody TAK-079, which binds CD38. CD38 is expressed on plasma and natural killer (NK) cells constitutively and upregulated on subsets of B and T lymphocytes upon activation. TAK-079 cross-reacts with CD38 expressed by cynomolgus monkeys and depletes subsets of NK, B, and T cells. Therefore, safety and function of TAK-079 was evaluated in this species, prior to clinical development, using bioanalytical, and flow cytometry assays. We pooled the data from eight studies in healthy monkeys (dose range 0...

Targeting survival mechanisms of immune cells may provide an avenue for immune intervention to dampen unwanted responses (e.g. autoimmunity, immunopathology and transplant rejection) or enhance beneficial ones (e.g. immune deficiency, microbial defence and cancer immunotherapy). The selective survival mechanisms of the various immune cell types also avails the possibility of specific tailoring of such interventions. Here, we review the role of the BCL-2 anti-apoptotic family members (BCL-2, BCL-XL, BCL-W, MCL-1 and A1) on cell death/survival of the major immune cell types, for example, T, NK, B, dendritic cell (DC) lineages...

PURPOSE: To evaluate the levels of peripheral blood CD34+  cells in women who subsequently had a spontaneous miscarriage (SM). MATERIALS AND METHODS: We enrolled 11 women who had SM, matching them for age, BMI and gestational age with 33 healthy pregnancies (controls). From a blood sample at 9th-11th weeks of pregnancy, we evaluated PAPP-A, free β-hCG, T (suppressor and helper), NK, B, CD34+  cells. RESULTS: In peripheral blood of women who had SM, PAPP-A and CD34+  cells were significantly lower (p < 0...

The CD11d integrin is expressed on the cell surface of leukocytes that belong to the myeloid lineage, but its expression on lymphocytes remains unexplored. To test the hypothesis that CD11d is expressed on lymphocyte subsets, we employed a multicolor flow cytometry panel to identify CD11d expression on B, NK, CD4+ and CD8+ αβ T cells (αβTc), and γδ T cells (γδTc) in human PBMC samples. CD11d was highly expressed on NK cells, B cells, and γδTc, but not αβTc. CD11d expression was higher on freshly isolated γδTc compared with αβTc from healthy donors, yet both inter- and intradonor variability was evident...