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关键词： HLA   HLA-C*16:01:01:42Q   novel allele   sequencing-based typing  

摘要： HLA-C*16:01:01:42Q differs from HLA-C*16:01:01:01 by one nucleotide substitution in the splicing site between intron 2 and exon 3.

关键词： Incident atrial fibrillation   NKT-like cell   T cell  

摘要： Aims:T cells are present in atrial tissue from atrial fibrillation (AF) patients. However, prospective studies of T cells and AF development are few. The current aim was to investigate if T-cell subsets are associated with the risk of developing AF. Methods and results:T-cell subsets, measured by flow cytometry of cryopreserved mononuclear leucocytes isolated from blood at baseline, were analysed for associations of incident AF in 669 subjects from a population-based cohort. Subjects were followed for incidence of AF for 18.6 (11.5-21.7) years during which 145 subjects were diagnosed with AF. Incident AF cases had higher levels of CD3CD56 NKT-like cells. No differences in CD3, CD3CD4, CD3CD8, Th1, Th2, or regulatory T cells between incident AF cases and non-cases were observed. Women had higher levels of NKT-like cells than men. High numbers of NKT-like cells were associated with an increased risk of developing AF in women [HR (95% CI) 1.88 (1.10-3.23) above vs. below median], but not in men or in the total cohort. The majority of NKT-like cells were IFNγ after stimulation. High numbers of IFNγ NKT-like cells were associated with increased risk for developing AF in women. Median fluorescence intensity of IFNγ for NKT-like cells was higher in cases of incident AF in women, but not in the total cohort or in men. Conclusion:High levels of IFNγ NKT-like cells in blood are associated with increased risk of incident AF in women, supporting a role for T cells in development of AF and emphasizing sex differences in this context.

关键词： Acute severe ulcerative colitis   Anti-TNF   Colectomy   Infliximab  

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.