课程文献中心 更多>>

关键词： Tumor necrosis factor alpha   eczema   mast cells   thymic stromal lymphopoietin  

摘要： Background: TNF-a is an important proinflammatory cytokine, but its neutralization in the management of inflammatory skin disorders like psoriasis may trigger eczematous skin lesions as an adverse reaction. Objectives: This study aimed to elucidate whether TNF-a may protect from skin inflammation and to identify in detail the underlying mechanisms. Methods: Wild-type, TNF-a-deficient, thymic stromal lymphopoietin (TSLP) receptor-deficient, mast cell (MC)-deficient, TNF-a-TSLP receptor double-deficient, and TNF-a-MC double-deficient mice were subjected to a skin inflammation model and inspected by physical, clinical, histologic, immunohistochemical, and bioanalytic techniques. Results: TNF-a deficiency promoted skin inflammation. This was accompanied by MC hyperplasia and potent TSLP production in lesional skin and serum of TNF-a-deficient mice. Specifically, MCs were found to be responsible for inducing high levels of TSLP in the epidermis, compromising barrier function and initiating inflammation. In contrast, the production of immunoglobulins, including IgE, was reduced in mice lacking TNF-a. Conclusions: TNF-a restrains MC-dependent TSLP production and the onset of eczema. (J Allergy Clin Immunol 2025;156:150-8.)

关键词： HLA-DQB1*03:01:01:76   HLA-genotyping   Illumina   next generation sequencing   novel allele  

摘要： The HLA-DQB1*03:01:01:76 allele differs from HLA-DQB1*03:01:01:03 by a single nucleotide substitution in intron 5.

关键词： Coccidiosis   Major histocompatibility complex   Alloantigen system   Disease resistance   Chicken  

摘要： Coccidiosis, a major poultry protozoal disease caused by several Eimeria species, compromises gut health causing significant losses. This study assessed the association of haplotypes of the major histocompatibility complex (MHC) and other blood alloantigens found in commercial egg production chickens with resistance to coccidiosis. Pedigreed White Leghorn offspring segregating for the MHC-B region, plus four additional alloantigen systems A (C4BPM), D (CD99), E (FCAMR), and I (RHCE) were tested for differential resistance to coccidiosis in five 26-day (d) trials (n= 235 birds in total). On d 19, all birds were inoculated with a cocktail of E. acervulina, E. maxima, and E. tenella oocysts and allocated to individual cages. Phenotypes evaluated included body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR), gross and microscopic lesion scores (GLS and MLS), and oocyst shedding (oocysts per gram, OPG). Haplotypes of the five blood systems were determined by SNP genotyping. A positive and negative association means an increase and decrease in a phenotypic trait, respectively, with each additional copy (0, 1 or 2) of a given haplotype. Results were considered statistically significant at P <= 0.05. The CD99-H01 haplotype association was positive with BWG but negative with FCR. Genotype B21B21 had the highest GLS in the jejunum establishing a positive association between MHC B21 and jejunal GLS. Further, the B12B15 genotype had a lower E. maxima OPG compared with the B12B21 genotype. The I system I-H01 haplotype had a negative association with jejunal and cecal GLS. Duodenal GLS was lower in E-H02/H02 compared to the E-H07/H07 genotype of the E system. Haplotypes B21, blood systems D-H01, E-H02, and I-H01 were associated with improved resistance to coccidiosis. The association of specific haplotypes of the MHC-B and other alloantigen systems D, E, and I with resistance and susceptibility traits during mixed Eimeria infection underscores the need for furthe

关键词： HLA   HLA-DQA1*06:06   new allele   next-generation sequencing  

摘要： The HLA-DQA1*06:06 allele differs from the HLA-DQA1*06:01:01:02 allele by a single nucleotide at codon 24 in exon 2.

关键词： antibody   HLA polymorphism   HPV16   IgG   IgM  

摘要： Little is known about the factors associated with the natural humoral immune response against human papillomavirus (HPV) infection. The association between HLA-DRB1 and -DQB1 polymorphism and (1) HPV16 DNA detection, (2) naturally developed humoral immune response (IgG and IgM) against HPV16 L1 and L2 capsid proteins, and (3) type of HPV16 infection (transient or persistent) was investigated. Data from 943 women participating in the Ludwig-McGill cohort study was analyzed. HLA-DRB1 and HLA-DQB1 genotyping was done by PCR-based methods. HPV DNA was assessed every 4 months during the first year of follow-up, and HPV16 IgG and IgM antibody measurements were performed by ELISA in serum samples from the first and/or second visits. Associations were estimated by adjusted logistic regression models. HLA-DRB1*03:02 was associated with HPV16 DNA positivity (OR = 2.49, 95% CI: 1.11-5.60). HLA-DRB1*13:01 and HLA-DQB1*04:02 were associated with low levels of HPV16 IgG antibodies (OR = 0.44, 95% CI:0.23-0.87;OR = 0.10, 95% CI: 0.02-0.55, respectively). Neither IgM HPV16 antibodies nor the type of HPV16 infection (transient or persistent) were associated with HLA-DRB1 or -DQB1 variants. HLA-DRB1 and -DQB1 polymorphism might be associated with different levels of IgG against HPV16 infection, but IgM production and the type of infection seem to occur independently of these variants.

关键词： alleles   haplotypes   histocompatibility testing   HLA polymorphism   HLA-DQB1 gene  

摘要： The new HLA-DQB1*03:575 differs from HLA-DQB1* 03:03:02:01 by a single base substitution at exon 2.

关键词： IL-5/IL-5R antagonists   Biologic   Severe asthma   Clinical trials   Asthma exacerbations   OCS use   Clinical remission  

摘要： BACKGROUND: Randomized controlled trials (RCTs) assessing the efficacy of IL-5/IL-5R antagonists showed a significant reduction in asthma exacerbations as well as a corticosteroid-sparing effect in selected patients with severe eosinophilic asthma. OBJECTIVE: To compare the response and remission rate after treatment with IL-5/IL-5R antagonists in patients with asthma who would or would not have met inclusion criteria of pivotal RCTs. METHODS: This was a retrospective cohort study of patients with severe eosinophilic asthma aged 18 and older treated with IL-5/IL-5R antagonists between 2012 and 2020 in a tertiary outpatient asthma clinic. Patients aged 75 years or younger, with a smoking history of less than 10 pack-years and a reversible FEV1 less than 80% predicted in the previous year were considered to fulfill the pivotal RCT inclusion criteria. Response to treatment and clinical remission of asthma were assessed in those who did or did not fulfill pivotal RCT inclusion criteria. RESULTS: A total of 108 subjects were included. Only 22 patients (20.4%) met all pivotal RCT inclusion criteria. There was no significant difference in response to treatment of these patients compared with those who did not fulfill inclusion criteria (odds ratio [95% CI] = 0.66 [0.15-2.85]). However, RCT eligibility was associated with a higher likelihood of achieving clinical remission (odds ratio [95% CI] = 4.09 [1.02-16.45]). CONCLUSION: IL-5/IL-5R antagonists seem to be as effective in subjects who would have been excluded from pivotal RCTs as in those who met the RCT inclusion criteria, but RCT eligibility increases the likelihood of achieving clinical remission of asthma. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/ 4.0/). (J Allergy Clin Immunol Pract 2025;13:1768-75)

关键词： HLA   HLA-C*06:406   novel allele   sequencing-based typing  

摘要： HLA-C*06:406 differs from HLA-C*06:02:01:01 by one nucleotide substitution in codon 201 in exon 4.

关键词： T2D   EIAS   Glycemic Variability   Insulin Antibodies   HLA   Proteomics  

摘要： Aims: Insulin antibodies (IAs) are prevalent in insulin-treated patients with diabetes and may cause immunological dysglycemia, known as exogenous insulin antibody syndrome (EIAS). This study aims to elucidate the clinical, genetic, and proteomic characteristics of patients with concurrent type 2 diabetes (T2D) and EIAS. Methods: This was a case-control study with 177 IA-positive and 177 IA-negative T2D patients receiving insulin therapy. Among the IA-positive group, 46 patients with hypoglycemia and aberrantly elevated molar ratio of insulin to C-peptide (ICPR > 1) were identified as EIAS cases, followed with human leukocyte antigen (HLA) genotyping and plasma proteomic analysis by Olink platform. Results: Patients with EIAS exhibited greater glycemic variability than patients in other groups (IA-positive ICPR <= 1 or IA-negative). Higher ICPR was associated with increased glycemic variability in the IA-positive group. DRB1*0405-DQA1*03-DQB1*0401, DRB1*0803-DQA1*0103-DQB1*0601, and DRB1*1501-DQA1*0102-DQB1*0502 are the susceptible HLA haplotypes for EIAS. Additionally, nine differentially expressed proteins were identified in EIAS patients, with GALNT3, IL10, and CCL28 showing promising diagnostic performance. Conclusions: IA-positive patients with remarkably elevated ICPR are prone to glycemic variability and should be evaluated for the diagnosis of EIAS. In this pilot study with limited sample size, EIAS is associated with unique HLA-DR-DQ risk haplotypes and enhanced immunoinflammatory response.

关键词： Crohn's disease   Mesenteric fat   Fibrogenesis   Group 1 Innate lymphoid cell  

摘要： Background Creeping fat is a characteristic of Crohn's disease and impacts the disease course. We evaluated creeping fat formation, focusing on innate lymphoid cell-mediated fibrogenesis and its clinical significance. Methods Patients with inflammatory lesions in the ileum (the most commonly affected area), who underwent surgical resection at Osaka University or Hyogo Medical University (n = 34), were included. The ileum and mesentery were obtained from three sites: the control, non-creeping fat part, and creeping fat part. The distribution and properties of the innate lymphoid cells were analyzed by cell isolation. Furthermore, the correlation between macrophages and their effects on adipose tissue and clinical course were also investigated in a prospective cohort study. Results Group 1 innate lymphoid cells in creeping fat were increased, correlating with inflammatory macrophages in the mesentery and showing higher interferon-gamma expression. Co-culture experiment involving stromal vascular fraction from the control mesentery and Group 1 innate lymphoid cells from creeping fat revealed increased mRNA expression of fibrosis-related genes and inflammatory markers of macrophages, although these changes were nullified by interferon-gamma-neutralizing antibody. Next, we examined the clinical importance of Group 1 innate lymphoid cells and identified their high frequency in creeping fat as a risk factor for early recurrence (P = 0.008, odds ratio: 1.19). Furthermore, the higher Group 1 innate lymphoid cell frequency group (>= 80%) had shorter relapse-free survival (P = 0.03). Conclusions Group 1 innate lymphoid cells and inflammatory macrophages contribute to creeping fat formation via interferon-gamma secretion, affecting post-surgery intestinal outcomes.