Human Immunology

BACKGROUND: Immigrants represented 21.8% of cases in a Spanish cohort of hospitalised patients with COVID-19, a proportion exceeding the percentage of immigrants in that area's total population. Among the ethnic-related genetic risk factors for COVID-19, human leukocyte antigen (HLA) genotypes in diverse populations might bias the response to SARS-CoV-2 infection and/or progression. Similarly, genetic differences in natural killer-activating and inhibitory receptors could play a role in the immune system's response to the viral infection...

Tumor necrosis factor alpha (TNFa) is an inflammatory cytokine that is involved in the pathogenesis of various inflammatory disorders including rheumatoid arthritis. TNF-alpha receptor I (TNFR1a) is one of the receptors TNFa binds with for its activation. Any variation in this receptor might affect the role of TNFa in successive events. Amino acid residue substitutions might happen in TNFR1a through non-synonymous single nucleotide polymorphisms (nsSNPs) which may alter the functioning of TNFa, hence, identifying any such substitutions is of paramount significance...

The aim of this study was to investigate the role of ubiquitin-specific peptidase 8 (USP8) in human trophoblast cells and its molecular mechanism. Based on the GSE30186 dataset, USP8 was identified as a downregulated gene in pre-eclampsia (PE). Analysis of clinical samples also revealed that USP8 expression at both the mRNA and protein levels in placental tissue from patients with PE was significantly lower than that from healthy pregnant women. Plate clone formation, scratch-wound healing, Transwell, tubule formation, and western blot assays collectively revealed that USP8 overexpression promoted the proliferation, migration, invasion, and pro-angiogenesis function of trophoblast cells, while USP8 knockdown induced the opposite effects...

BACKGROUND: The Cancer Epitope Database and Analysis Resource (CEDAR) is a newly developed repository of cancer epitope data from peer-reviewed publications, which includes epitope-specific T cell, antibody, and MHC ligand assays. Here we focus on prostate cancer as our first cancer category to demonstrate the capabilities of CEDAR, and to shed light on the advances of epitope-related prostate cancer research. RESULTS: The meta-analysis focused on a subset of data describing epitopes from 8 prostate-specific (PS) antigens...

Sepsis is a dysregulated immune response to infections that frequently precipitates multiple organ dysfunction and death despite intensive supportive therapy. The aim of the present study was to identify sepsis-induced alterations in the signaling transcriptome of peripheral blood leukocytes that might shed light on the elusive transition from proinflammatory to anti-inflammatory responses and underlie long-term post-sepsis immunosuppression. Peripheral blood leukocytes were collected from subjects (i) with systemic inflammation, (ii) with sepsis in the acute phase and (iii) 6 months after recovery from sepsis, corresponding to progressive stages of the disease...

Previously, we established that as a function of its mode of interaction with its ligand or cellular conditions such as membrane lipids, preexisting signaling intermediates activation status, a transmembrane receptor, as represented here with CD40, can induce counteractive cellular responses. Using CD40-binding peptides, recombinant mutated CD40-ligands, and an agonistic antibody, we have established the functional duality of CD40. CD40 builds up two constitutionally different signalosomes on lipid raft and non-raft membrane domains initiating two different signaling pathways...

Immunopathology in human tuberculosis affects T-cell phenotype and functions. Previous studies identified impaired T-cell sensitivity to Interleukin (IL)-7 accompanied by lower IL-7 receptor α-chain (IL-7Rα) expression in patients with acute tuberculosis. In the present study, we characterized affected T-cell subsets and determined the influence of tuberculosis disease severity and treatment response. Tuberculosis patients (n = 89) as well as age- and gender-matched asymptomatic contacts (controls, n = 47) were recruited in Ghana...

Autoimmune thyroid disease (AITD) is a T lymphocytes-mediated autoimmune disorder affecting pregnant women. The current study sought to determine the correlations between T helper-1 (Th1)/T helper-2 (Th2) cytokines and regulatory T cells (Tregs) and T cell subsets and pregnancy outcomes in AITD patients during early pregnancy (T1), middle pregnancy (T2), late pregnancy (T3), and postpartum period (PP). A total of 60 patients with Graves' disease, 60 patients with Hashimoto's thyroiditis, and 30 healthy pregnant women were initially enrolled in the study...

BACKGROUND: Immune response to several kidney self-antigens (KSAg) such as Collagen IV (Col-IV), Perlecan (PL), and Fibronectin (FN) have been associated with antibody-mediated damage and poor allograft survival. Thus, the aim of this study was to determine if humoral immune responses to KSAg correlates with progression of chronic immune injury (CII) changes at 1 year or 2 years. METHODS: Kidney transplant recipients who underwent 1- or 2-year biopsies, with chronic interstitial inflammation (ci > 1) and/or glomerular membrane double contouring (cg > 0) were analyzed with matched controls...

Initially discovered in chronic viral infection and then extended to tumor, 'T-cell exhaustion' is a broad term describing the response of T cells to chronic antigen stimulation. By definition, whether T-cell exhaustion occurs in diffuse large B-cell lymphoma (DLBCL) remains largely unknown because little has been described. Here, the immune-suppressing checkpoint molecules involved in T-cell exhaustion, including PD-1, PD-L1, TIM-3 and TIGIT, whose expression levels were analyzed in DLBCL, were retrieved from the GEPIA database...

Endometriosis presents a pro-inflammatory microenvironment influenced by cytokines, such as interleukin (IL)-8, which expression may be influenced by genetic polymorphisms. Therefore, we aimed to investigate the role of interleukin (IL)-8 rs4073 polymorphism in endometriosis' development and its related symptoms. A case-control study was conducted with 207 women with endometriosis and 193 healthy controls. Polymorphism was genotyped using a TaqMan validated assay. Associations were evaluated by binary logistic regression, using odds ratios (OR) and 95 % confidence intervals (CI), and P ≤ 0...

BACKGROUND: Immune checkpoint blockade (ICB) is considered as a promising approach for cancer treatment. However, the potency of ICB therapy in yolk sac tumors (YSTs) has not been confirmed, and the comprehensive analysis of tumor immune microenvironment and the expression of PD-1/PD-L1 and CTLA4 were also not thoroughly evaluated. METHODS: Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tumor specimens from 23 YSTs patients to detect the density and distribution of tumor-infiltrating T cells, tertiary lymphoid structures (TLSs), as well as the expression of PD-1/PD-L1 and CTLA4...

Kawasaki disease (KD) is an acute pediatric vasculitis that predominantly affects children under the age of 5 years. To date, genome-wide association studies (GWAS) have identified several KD susceptibility genes (e.g., BLK, CD40, FCGR2A, BCL2L11, and IGHV), which are mainly involved in B cell immunity. In this study, we aimed to identify additional KD susceptibility genes mainly involved in B cell development and functions by analyzing our previous GWAS data and conducting a replication study using new sample...

BACKGROUND: T helper 17 (Th17) cells produce IL-17A cytokine and can exacerbate autoimmune diseases and asthma. The β2 adrenergic receptor is a g protein-coupled receptor that induces cAMP second messenger pathways. We tested the hypothesis that terbutaline, a β2-adrenergic receptor-specific agonist, promotes IL-17 secretion by memory Th17 cells in a cAMP and PKA-dependent manner. METHODS: Venous peripheral blood mononuclear cells (PBMC) from healthy human participants were activated with anti-CD3 and anti-CD28 antibodies...

The aim of this study was to establish the role of thymic stromal lymphopoietin (TSLP) in the intra-amniotic host response of women with spontaneous preterm labor (sPTL) and birth. Amniotic fluid and chorioamniotic membranes (CAM) were collected from women with sPTL who delivered at term (n = 30) or preterm without intra-amniotic inflammation (n = 34), with sterile intra-amniotic inflammation (SIAI, n = 27), or with intra-amniotic infection (IAI, n = 17). Amnion epithelial cells (AEC), Ureaplasma parvum, and Sneathia spp...

The question of which protein antigens, such as HLA class I or class II molecules, will bind, and how well, to a given antibody is often assumed to depend exclusively on the details of protein surface structure. These structures are usually based on static models resulting from X-ray crystallography. While these notions are useful, the ultimate causal factors determining how well a given antigen binds a given antibody are based in thermodynamics and can include atomic mobility and the time-varying conformations of proteins...

BACKGROUND: CKD is a major cause of morbidity and mortality worldwide. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Recent investigations have demonstrated that IFNλ plays an important role in the pathogenesis of autoimmune and inflammatory diseases. However, the association of IFNλ with CKD is still poorly understood. OBJECTIVE: To analyze the correlation between IFNλ levels and pro-inflammatory cytokines, and to investigate the effect of IFNλ on PBMCs in patients with CKD...

NRAMP1 and VDR gene polymorphisms have been variably associated with susceptibility to tuberculosis (TB) amongst populations having different genetic background. NRAMP1 and VDR gene variants' association with susceptibility to active infection by Mycobacterium tuberculosis (Mtb) was analyzed in the Warao Amerindian population, an ethnic population from Venezuela's Orinoco delta region. Genomic DNA was extracted from individuals with and without TB to evaluate genetic polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)...

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Cardiovascular diseases (CVDs) have emerged as the leading cause of mortality globally, with atherosclerosis being a prominent focus of investigation among medical researchers worldwide. Atherosclerosis is characterized as a disease of the large and medium-sized arteries that is multifocal, accumulative, and immunoinflammatory in nature, resulting from the deposition of lipids. Accumulating evidence suggests that inflammatory responses and immunoregulation play a vital role in the occurrence and development of atherosclerosis...