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关键词： HLA   next-generation sequencing   novel allele  

摘要： HLA-A*29:01:15 differs from HLA-A*29:01:01:01 by a single nucleotide change in exon 1, 39 C -> G (codon -12.3 CTC -> CTG).

关键词： Interleukin-26   Monoclonal antibodies   T cells   Macrophages   Bacterial infection  

摘要： Interleukin-26 (IL-26) belongs to the IL-10 cytokine family and exerts diverse biological functions in regulating immune responses in vertebrates. Although IL-26 has been extensively studied in mammals, the functions of IL- 26 remain largely unexplored in lower vertebrates. In this study, we determined the tissue and cell sources of IL- 26 using a monoclonal antibody (mAb) generated against grass carp (Ctenopharyngodon idella, Ci) IL-26, and investigated the responses of IL-26 producing cells to bacterial infection. We showed that the CiIL-26 mAb specifically recognized the recombinant CiIL-26 proteins expressed in the Escherichia coli and HEK293 cells. Flow cytometry analysis revealed that the CiIL-26 mAb could detect the intracellular CiIL-26 expressed in the HEK293 cells and CIK cells stimulated with inactivated Aeromonas hydrophila (A. hydrophila). Using confocal microscopy, we analyzed IL-26+ cells in various tissues of grass carp following infection with A. hydrophila. It was shown that the IL-26+ cells were significantly increased in the gills, head kidney, posterior intestine and spleen. Remarkably, for the first time, we observed that most IL-26+ cells were CD3 gamma/delta+ T cells and MCSFR+ monocytes/macrophages, which could be induced by A. hydrophila. Our findings highlight the essential roles of CD3 gamma/delta+/IL-26+ T cells and MCSFR+/IL-26+ macrophages in the immune defense against bacterial infections in fish.

关键词： Tuberculosis   Class I & II MHC epitopes   Cell mediated immunity   Vaccine candidate  

摘要： Tuberculosis (TB) remains a global health challenge as annual mortality rate due to drug resistant TB is increasing exponentially. This is mostly associated with the delayed diagnosis of Multidrug-resistant (MDR) or latent TB. Effective management of TB demands development of novel immunological strategies, such as peptidebased/subunit vaccines that can stimulate specific immune responses. In this context, we evaluated the immunogenic potential of two Major Histocompatibility Complex (MHC) Class I/II-restricted peptides from Mycobacterium tuberculosis (M. tuberculosis): Rv2588c and Rv0148. The peptides were tested on T and monocyte populations from healthy donors and pulmonary TB (PTB) patients. Flow cytometry analysis revealed significant T cell activation in peripheral blood mononuclear cells (PBMC) from both groups. Enzyme-linked immunosorbent assay (ELISA) demonstrated a strong IFN-gamma response, confirming effective T cell activation. Additionally, these peptides induced increased nitric oxide (NO) production in macrophages, indicating their role in activating the innate immune system. Overall, Rv2588c and Rv0148 peptides exhibited robust immunogenicity, stimulating both adaptive and innate immune responses in PBMCs from healthy and PTB individuals. These findings highlight their potential as promising TB vaccine candidates, paving the way for improved TB treatment and prevention strategies.

关键词： ovarian cancer   lncRNA   ZNF667-AS1   tumor necrosis factor  

摘要： Ovarian cancer (OC) is the most lethal gynecological malignancy and poses a significant public health burden. The present study explored the function and mechanism of long noncoding RNA (lncRNA) ZNF667-AS1 in OC progression. The present study conducted a multifaceted evaluation, including transcriptomic analyses, to examine the expression and prognostic value of lncRNA ZNF667-AS1 in OC via the Cancer Genome Atlas and Genotype-Tissue Expression data. In vitro experiments on OC cell lines were used to investigate the functional effect of ZNF667-AS1 via cell proliferation, migration and invasion assays and RNA sequencing and western blotting were used to explore the implicated molecular pathways. ZNF667-AS1 was significantly underexpressed in OC tissues and cell lines. Its expression levels were positively associated with improved patient prognosis and affected both tumor behavior and tumor microenvironment interactions. Functional analysis confirmed the tumor-suppressive role of ZNF667-AS1 and revealed a marked decrease in proliferation, migration and invasion in ZNF667-AS1-overexpressing cells. Additionally, ZNF667-AS1 was identified as a key regulator in the tumor necrosis factor signaling pathway, which suggests a strong link between ZNF667-AS1 expression and OC progression. The present study identified ZNF667-AS1 as a potential biomarker for OC prognosis and treatment and illustrated its significant regulatory effects on the TNF pathway and its broader implications in cancer pathobiology.

关键词： HLA-C   new allele   NGS   silent mutation  

摘要： Sequences of the novel HLA-C*02:31:02, -C*12:03:95, -C*12:03:96 and -C*17:03:06 alleles identified in Russian individuals.

关键词： dapsone hypersensitivity syndrome   severe cutaneous adverse reactions   TNFR   TNF-alpha   VISTA  

摘要： BackgroundSevere cutaneous adverse reactions (SCARs) mediated by cytotoxic T lymphocytes are a series of life-threatening conditions with a mortality of 4%-20%. The clinical application of tumor necrosis factor-alpha (TNF-alpha) antagonist improves the outcome of some SCARs patients;however, this is complicated by the elusive and varied *** investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to *** clarify the precise process and optimize the therapy regimen of SCARs, we performed single-cell sequencing, in vitro functional and clinical analysis of patients with *** observed that TNF-alpha breaks drug-specific T-cell tolerance by inhibiting the expression of V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA). Furthermore, TNF-alpha generated a positive feedback loop in the early phase of drug-specific T-cell activation, whereby B cells acted reciprocally on the corresponding T cells to reinforce TNF-alpha cytokine expression. In contrast, this pathway of TNF-alpha-VISTA signaling did not operate in memory effector T cells. Drug-specific memory effector T-cell responses were inhibited by increasing Treg cell expression in a negative feedback loop, with TNF-alpha antagonists preventing the inhibitory effect. These observations align with the clinical analysis that early but not late intervention with TNF-alpha antagonists significantly improved outcomes in SCARs *** findings defining feedback regulation of VISTA and Treg cells by TNF-alpha in different stages of the drug-specific T-cell response and, indicate that a Treg agonists, instead of TNF-alpha antagonists, could be used for treatment of patients with progressive SCARs.

摘要： Background: Several studies report that ashwagandha, a traditional Ayurvedic supplement, has anti-inflammatory properties. Type 2 (T2) asthma is characterized by eosinophilic airway inflammation. Objective: We hypothesized that allergen-induced eosinophilic airway inflammation in mice would be reduced following administration of Withaferin A (WFA), the primary active phytochemical in Ashwagandha. Materials and Methods: C57BL/6J mice were given 10 total intra-peritoneal injections of 2 mg/kg WFA or vehicle control, concurrent with 6 total intranasal administrations of 50 mu g house dust mite extract (HDM) or saline control over 2 weeks. Results: We observed that treatment with WFA reduced allergen-induced peribronchial inflammation and airway eosinophil counts compared to mice treated with controls. In addition, we observed that treatment with WFA reduced lung levels of interleukin-25 (IL-25) but increased lung gene expression levels of its co-receptor, Il17ra, in HDM-challenged mice compared to HDM-challenged mice that received the vehicle control. Conclusion: This study pinpoints a potential mechanism by which WFA modulates allergen-induced airway eosinophilia via the IL-25 signaling pathway. Future studies will investigate the effects of WFA administration on lung eosinophilia and IL-25 signaling in the context of chronic allergen-challenge.

摘要： The novel allele A*68:02:26 differs from A*68:02:01:01 by one nucleotide substitution in exon 8.

关键词： inflammatory bowel disease   IBD   Crohn's disease   TNF  

摘要： Background: As the use of anti-tumor necrosis factor-alpha (TNF alpha) therapies in Crohn disease (CD) is spread, the loss-of-response (LOR) to it is increasingly encountered. Discovering a pathological pathway and biomarkers that can predict LOR would assist in the management of patients with CD. In this article, we provide a comprehensive systematic review of studies assessing predictors of immunogenicity and loss-of-response to anti-TNF alpha drugs in patients with CD. Data sources: We performed a systematic review of PubMed to identify citations pertaining to predictors of immunogenicity and loss-of-response to anti-TNF alpha drugs in patients with CD through April 27, 2024, using a predefined string of keywords. Data extraction and quality assessment were performed independently by 2 reviewers. Results: A total of 18 eligible studies were included in the review. Four major groups of studies were identified: genetic factors, factors linked with colonic inflammation, serum and anthropological markers, and prevention of LOR. Promising predictors of LOR to infliximab or adalimumab include the carriage of HLA-DQA1*05, visceral adiposity, intestinal abundant presence of CD96, IL-17, and IL-23. Substantial heterogeneity was observed, and none of the markers had undergone formal validation. Specific limitations to acceptance of these factors included failure to use a standardized definition of LOR to anti-TNF alpha treatment, lack of specificity, and insufficient relevance to the pathogenesis of LOR. Conclusions: This review underlines the lack of well-defined studies and controlled trials investigating predictors of LOR to anti-TNF alpha therapies in CD. A research priority is the development of reliable and accurate biomarkers that can shed light on the pathogenesis of the implied LOR. These biomarkers, along with genetic factors, have the potential to enhance clinical management by aiding in patient stratification and monitoring.