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关键词： HLA   HLA-B*35:628   novel allele   sequencing-based typing  

摘要： HLA-B*35:628 differs from HLA-B*35:01:01:01 by one nucleotide substitution in codon 109 in exon 3.

关键词： HLA   HLA-C*07:1172   NGS   novel allele  

摘要： HLA-C*07:1172 differs from HLA-C*07:01:01:01 by a single nucleotide substitution in Codon 7 in Exon 2.

关键词： Malaria   Collagen-induced arthritis   Interleukin-10   Autoimmunity   Plasmodium yoelii 17XNL  

摘要： We previously reported that Plasmodium yoelii 17XNL (Py), a non-lethal rodent malarial parasite, could suppress collagen-induced arthritis (CIA) and increase the production of T cell-derived interleukin (IL)-10. However, it remained unclear whether IL-10 is essential for the Py-induced suppression of CIA. Male IL-10 knockout (KO) DBA/1 J mice were immunized with bovine type II collagen (CII) and subsequently infected with Py at one week post-immunization. The development of arthritis was evaluated by an arthritis score up to 6 weeks postimmunization. At 3 weeks post-immunization, cytokine production from splenocytes and serum anti-CII IgG/ IgG1/IgG2a levels were compared between non-infected control mice and Py-infected mice. Py infection inhibited the development of CIA in IL-10KO mice until 4 weeks post-immunization, after which the arthritis score reached levels comparable with the control mice. Both pro-arthritic (IL-17 and TNF-alpha) and anti-arthritic (IFN-gamma and IL-4) cytokines were down-regulated during the periods of parasitemia, while no significant differences were observed in levels of anti-CII IgG antibodies. Our findings indicate that Py alleviates CIA via IL-10independent mechanisms.

关键词： HLA-A antigens   HLA-B antigens   Donors   Platelet transfusion  

摘要： Administeringhuman leukocyte antigen (HLA)-compatible platelets is a tactic for treatingpatients with poor responses to random platelet injections. HLA-matched platelet provision requires many donors with HLA-typed and organized information. This study, the first of its kind in Iran, aimed to develop a registry system of HLA-typed platelet donors to facilitate the provision of compatible platelets to patients, leveraging the diversity of HLA alleles across Iran's various provinces. This study involved the HLA-typing of 1850 plateletpheresis donors, who were also registered as unrelated stem cell donors, across all blood centers in Iran from 2015 to 2022. HLA-A and HLAB genotyping was conducted at a low-resolution using polymerase chain reaction-sequence specific primers (PCR-SSP) and real-time PCR. Statistical analysis was performed to determine allelic genotypes and donor profiles. The majority of the donors were male (99.7%), with a mean age of 36 years. The high donor rate in Tehran indicates a larger pool of potential HLA-platelet donors due to a denser population and more donation facilities. The donors were recruited for HLA-compatible plateletpheresis. The frequency of HLA-AB alleles among donors was relatively consistent with those documented by Iranians. Our findings can be utilized to create a foundational HLA database. A registry system for HLAtyped platelet donors is crucial due to high HLA polymorphism and ethnic diversity. This system facilitates the rapid identification of compatible donors based on HLA typing. Additional inquiries are needed to expand the plateletpheresis registry and make a request-supply mechanism between the Iranian Blood Transfusion Organization and hospitals.

关键词： HLA   HLA-A*02:1198   novel allele   sequencing-based typing  

摘要： HLA-A*02:1198 differs from HLA-A*02:01:01:01 by one nucleotide substitution in codon -22 in exon 1.

关键词： biologic treatment   drug resistance   il-17 blockers   ixekizumab   psoriasis treatment  

摘要： Monoclonal antibodies, particularly interleukin-17 (IL-17) inhibitors like secukinumab and ixekizumab, have significantly advanced the treatment of severe plaque psoriasis. Clinical guidelines suggest changing biologic classes after primary treatment failure and consider switching within the same class or to a different class for secondary failures. Secondary failure was defined as the loss of response (PASI > 50% of initial value) in a patient who had previously achieved PASI 50 response at weeks 12-16. We present a case series of five male patients with chronic plaque psoriasis, each with disease durations of 9 to 16 years. When initially treated with secukinumab (300 mg weekly for five weeks, then monthly), all patients achieved Psoriasis Area and Severity Index (PASI 90) within 4 to 12 weeks. However, they experienced secondary loss of response after 9 to 16 months, qualifying as secondary biologic failure. We then switched to ixekizumab, starting with 160 mg, followed by 80 mg every two weeks for three months, and then monthly. Significant clinical improvement was observed within two weeks of starting ixekizumab, with all patients achieving and maintaining near-clear skin (PASI 90) by six months, without significant adverse effects. This approach is particularly relevant in regions with high latent tuberculosis prevalence where TNF-alpha inhibitors are less viable. Further research is needed to confirm these results in larger cohorts.

关键词： Heat-sterilized Lactobacillus crispatus strain KT-11   Lactic acid bacteria   Immune function   SARS-CoV-2 IgG   T cell   BMI   body mass index   CI   confidence interval   CRO   contract research organization   EMM   estimated marginal mean   HLA-DR   human leukocyte antigen-DR isotype   IFN   interferon   KT-11   Lactobacillus crispatus strain KT-11   MFI   mean fluorescence intensity   NK   natural killer   pDC   plasmacytoid dendritic cell   PPS   per-protocol analysis set   Scr   screening test   SD   standard deviation   Th   helper T   week 4   4 weeks postintervention   ΔWeek 4   amount of change from Scr to week 4  

摘要： Viral infections are a global public health threat, reaffirming the importance of immune function. We previously identified Lactobacillus crispatus strain KT-11 (KT-11) and found that heat-sterilized KT-11 affect counts of T cell and dendritic cell in vitro , as well as promoted immunoglobulin A production and prevented weight loss caused by influenza virus infection in vivo . It was hypothesized that heat-sterilized KT-11 affects immune cell count/activity even in healthy individuals. We conducted a pilot study to examine the design to verify the effects of heat-sterilized KT-11 supplementation on immune cell count/activity and physical condition. This was a pilot randomized, double-blind, placebo-controlled, parallel-group study including 22 healthy adults who consumed either KT-11 or placebo for 4 weeks. Immunological status (immune cell count/activity and its score) and various immune-related indicators including SARS-CoV-2 immunoglobulin G antibody were assessed, and a physical condition questionnaire was administered. The primary outcome was immune cell count/activity (T cell subsets, B cell, natural killer cell) and overall immunological status score after 4 weeks. Two patients were excluded because of noncompliance;the final analysis included 20 participants (10 participants/group). The KT-11 group had a significantly higher CD3+ T cell count versus placebo group. The female subgroup also had a significantly higher CD8+ CD28+ T cell count. Although the KT-11 group showed no changes in SARS-CoV-2 immunoglobulin G titer, it had fewer self-reported common cold-like symptoms, particularly fatigue. This pilot study showed that KT-11 affected immune cell profiles, suggesting that the feasibility of a verification study. This trial was registered at UMIN Clinical Trials Registry (UMIN000046991). (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： IL-33   CBP/(3-catenin   Wnt   Colon   Epithelium  

摘要： Interleukin (IL)-33 is a key responder to intestinal injury and inflammation. In the colon, it is expressed by several cell populations, with the specific cellular source likely determining its role. The colonic epithelium expresses IL-33;however, the factors controlling its production and the specific epithelial lineage(s) expressing IL-33 are poorly understood. We recently reported that colonic epithelial IL-33 is induced by inhibition of glycogen synthase kinase-3(3 (GSK3(3), but the signaling pathway mediating this induction is unknown. Here we tested the role of Wnt/(3-catenin signaling in regulating colonic epithelial IL-33 at homeostasis and in injury- induced colitis. Transcriptomic analysis shows that epithelial IL-33 localizes to stem and progenitor cells. Ligand activation of Wnt/(3-catenin signaling induced IL-33 in colonic organoid and cell cultures. Furthermore, small-molecule disruption of (3-catenin interaction with cyclic AMP response element binding protein (CBP) prevented epithelial IL-33 induction. Antagonism of CBP/(3-catenin signaling also prevented rapid epithelial IL- 33 induction in dextran sodium sulfate (DSS)-mediated colitis, and was associated with maintenance of crypt- expressed host defense peptides. Together, these findings show (3-catenin-driven production of epithelial IL-33 is an early response to colonic injury that shapes the crypt base defense response and suggest an immunoregulatory role for the stem cell niche in tissue injury.

关键词： HLA-A*01:478   new allele   next-generation sequencing  

摘要： HLA-A*01:478, a novel HLA class I allele detected by next-generation sequencing.

关键词： DNA methylation   periapical periodontitis   tumour necrosis factor-alpha  

摘要： Aim: Epigenetic regulation of the key inflammatory genes plays a crucial role in controlling monocyte/macrophage-mediated local and systemic responses to bacterial challenges. However, it has not been addressed in apical periodontitis (AP). We aimed to explore the methylation pattern of the TNF-alpha gene promoter and its association with the inflammatory phenotype of peripheral blood monocytes from individuals with AP and controls. Methods: A cross-sectional study was conducted, including otherwise healthy individuals with AP (n = 25) and controls (n = 29). Monocytes were isolated from the volunteer's blood samples using a Ficoll gradient followed by negative immunoselection. RNA and DNA were extracted. The DNA methylation profiles of the TNF-alpha gene promoter region were analyzed using bisulfite sequencing PCR. The mRNA expression levels of DNA methyltransferases 3a (DNMT3a) and Ten Eleven Translocation enzymes 1(TET1) were assessed by qPCR. A fraction of primary monocytes was also cultured for 24 h, and the supernatant was collected to measure cytokine levels through a Luminex assay. Generalized structural equation models (GSEM) evaluated the association between AP, DNA methylation, and TNF-alpha protein expression controlled for potential covariates. Models included the effect of the methylation of TNF-alpha gene promoter as a mediator of the association between AP and TNF-alpha protein expression levels. Results: Monocytes from AP individuals exhibited a heightened secretion of TNF-alpha and IL-1 beta and hypomethylation of the TNF gene promoter (p < .05). AP diagnosis was associated with the TNF-alpha gene promoters hypomethylated profile and enhanced pro-inflammatory cytokine levels, while lower methylation of the gene promoter region and -163 CpG single site mediated TNF-alpha overexpression (p < .05). Conclusions: DNA hypomethylation at the TNF-alpha gene mediates a proinflammatory phenotype in monocytes from AP patients, supporting a role i