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关键词： HLA   HLA-A*31:239   NGS  

摘要： HLA-A*31:239 has a single nucleotide substitution at position 329C>G when compared to the A*31:01:02:01 allele.

关键词： HLA-DQA1*05:05:13:02   next generation sequencing (NGS)   novel allele  

摘要： The novel HLA-DQA1*05:05:13:02 allele differs from its most closely related allele DQA1*05:05:01:01 in exon 4.

关键词： cytomegalovirus   HLA-E   HLA-G   NK cell   T lymphocyte  

摘要： HLA-E and -G class Ib molecules were considered unrelated to viral antigen presentation. HLA-E binds nonamers from the leader sequences of other HLA-I molecules and the human cytomegalovirus (HCMV) UL40 protein, interacting with CD94/NKG2 NK cell receptors. Yet, evidence that HLA-E may present some pathogen-derived peptides to CD8+ T lymphocytes has been reported. By contrast, HLA-G binds a broad spectrum of endogenous sequences but its role in antigen presentation is unknown. An experimental approach was set up to search for HCMV antigens displayed by HLA-G in infected cells. Among the analysed peptidome, 22 sequences corresponding to 16 HCMV molecules were identified;17 peptides were confirmed to interact in vitro with HLA-G of which 10 displayed characteristic anchor residues. As compared to the response in short-term (6 h) assays to immunodominant IE-1 and pp65 antigens, none of the HLA-G-binding peptides stimulated cytokine production by CD8+ T cells from HCMV-seropositive blood donors (n = 15). Following a 14-day peptide stimulation of PBMC and expansion with IL-2, CD8+ T cells specifically responding to a subset of these viral antigens were detected in some individuals, yet were not restricted by HLA-G in functional assays. A subset of viral peptides did bind to both HLA-G and -E but were not recognised by CD94/NKG2 NK cell receptors. Our results provide the first evidence that HLA-G may display potentially immunogenic viral peptides in HCMV-infected cells, yet do not support their ability to promote HLA-G-restricted CD8+ T cell responses nor to modulate NK cell functions.

关键词： Rheumatoid arthritis   Autoimmune disease   Monocyte subsets   Classical monocytes   Intermediate monocytes   FIL1Z(IL-37)   FCGR1A(CD64)   In silico analysis  

摘要： Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases. Chronic joint inflammation and bone destruction were shown to be caused by expanded monocytes in RA affected individuals. Interleukin-37 which known as FIL1Z(IL-37) is a well-known anti-inflammatory cytokine that plays a negative regulatory role of inflammation in RA. A total of 48 RA patients were divided equally into active RA group and stable RA group using the Disease Activity score (DAS)-28 score. Twenty-four age-and sex-matched healthy subjects were enrolled as controls. The expression level of Fc gamma receptor IA (FCGR1A(CD64)) on monocytes and their subsets in peripheral blood were assessed by flow cytometry (FC) and serum levels of FIL1Z(IL-37) were measured by ELISA. The mean fluorescence intensity (MFI) of FCGR1A(CD64) expressing classical and intermediate monocyte subsets and serum levels of FIL1Z(IL-37) were significantly elevated in RA patients compared to the control and positively correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and DAS-28 scores. The MFI of FCGR1A(CD64) expressing classical monocyte and serum levels of FIL1Z(IL-37) were significantly elevated in the active RA group compared to the stable RA group. The serum concentration of FIL1Z(IL-37) revealed very high specificity but limited sensitivity in discriminating between active and stable RA patients. Our results demonstrate a strong correlation between serum levels of FIL1Z (IL-37) and FCGR1A(CD64) expression on activated monocytes and their subsets in peripheral blood of RA patients. The results also depict that activated monocytes and their subsets may contribute to the elevated levels of FIL1Z(IL37) during an active disease status to counter-act the inflammatory process.

关键词： cardiac adaptations   exercise   interleukin-6   rheumatoid arthritis  

摘要： Interleukin-6 inhibitors (IL-6i) are commonly used in patients with rheumatoid arthritis to reduce inflammation from chronically increased IL-6. IL-6 levels increase transiently following exercise, exerting numerous positive effects. This study examined if beneficial exercise-induced cardiac adaptations were attenuated in patients with rheumatoid arthritis in concomitant IL-6i treatment compared with tumor necrosis factor inhibitors. Compared with control, we found that the tumor necrosis factor inhibitor-treated group, but not the IL-6i group, had a significant increase in left ventricular mass following 12 weeks of supervised exercise. However, the interaction effect of treatment modalities on exercise-induced cardiac adaptations was insignificant. (Exercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During IL-6 vs TNF Antibody Therapy;NCT05215509) (JACC Basic TranslSci. 2025;10:551-563) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： binding orientation   cross-linking   epitope mapping   mass spectrometry   reverse binding   sulfo-SDA  

摘要： T cell receptors (TCRs) recognize specific peptides presented by human leukocyte antigens (HLAs) on the surface of antigenpresenting cells and are involved in fighting pathogens and cancer surveillance. Canonical docking orientation of TCRs to their target peptide-HLAs (pHLAs) is essential for T cell activation, with reverse binding TCRs lacking functionality. TCR binding geometry and molecular interaction footprint with pHLAs are typically obtained by determining the crystal structure. Here, we describe the use of a cross-linking tandem mass spectrometry (XL-MS/MS) method to decipher the binding orientation of several TCRs to their target pHLAs. Cross-linking sites were localized to specific residues and their molecular interactions showed differentiation between TCRs binding in canonical or reverse orientations. Structural prediction and crystal structure determination of two TCR-pHLA complexes validated these findings. The XL-MS/MS method described herein offers a faster and simpler approach for elucidating TCR-pHLA binding orientation and interactions.

关键词： ulcerative colitis   transcriptomics   mitochondria   anti-TNF  

摘要： Background Recent studies hint at mitochondrial genes influencing UC patient response to anti-TNF treatment. We evaluated this hypothesis by following a targeted strategy to identify gene expression that captures the relationship between mitochondrial dysregulation and response to treatment. Our objective was to initially examine this relationship in colon samples and subsequently assess whether the resulting signal persists in the *** We analyzed the transcriptome of colon samples from an anti-TNF-treated murine model characterized by impaired mitochondrial activity and treatment resistance. We then transferred the findings that linked mitochondrial dysfunction and compromised treatment response to an anti-TNF-treated UC human cohort. We next matched differential expression in the blood using monocytes from the peripheral blood of controls and IBD patients, and we evaluated a classification process at baseline with whole blood samples from UC *** In human colon samples, the derived gene set from the murine model showed differential expression, primarily enriched metabolic pathways, and exhibited similar classification capacity as genes enriching inflammatory pathways. Moreover, the evaluation of the classification signal using blood samples from UC patients at baseline highlighted the involvement of mitochondrial homeostasis in treatment *** Our results highlight the involvement of metabolic pathways and mitochondrial homeostasis in determining treatment response and their ability to provide promising classification signals with detection levels in both the colon and the bloodstream. Research suggests mitochondrial dysfunction may compromise response to anti-TNF treatment in UC patients. Testing this, we induced mitochondrial dysregulation in a mouse model treated with anti-TNF and linked gene expression to non-response. The findings were then corroborated on human cohorts.

关键词： HLA   HLA-DPB1*104:01:08   novel allele   sequencing-based typing  

摘要： HLA-DPB1*104:01:08 differs from HLA-DPB1*104:01:01:04 by one nucleotide substitution in codon 199 in exon 4.

关键词： blood-brain barrier   cognitive impairment   Creutzfeldt-jakob disease   epileptic encephalopathy   IL-1 beta   IL-8  

摘要： Inflammatory cytokines play a crucial role in Creutzfeldt-jakob disease (CJD). We examined inflammatory cytokine levels in both blood and CSF in a CJD patient and an epileptic encephalopathy as a control case. Results showed that IL-6, IL-8, IL-1 beta, and TNF-alpha levels were elevated in blood, but only IL-8 and IL-1 beta levels, especially IL-8, were significantly elevated in Cerebrospinal fluid (CSF). This suggests that IL-8 and IL-1 beta are closely related to cognitive impairment and blood-brain barrier (BBB) damage in CJD, and IL-8 might be a key target in early cognitive impairment in CJD.

关键词： allele variant   next-generation sequencing   novel allele  

摘要： Allele variants HLA-A*02:11:01:08 and HLA-A*11:01:01:91 differ from HLA-A*02:11:01:01 and HLA-A*11:01:01:01 by a single nucleotide respectively.