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关键词： limbal stem cell deficiency   cornea   epithelium   macrophages   monocytes   inflammation   TNF-alpha   therapy  

摘要： Purpose: Ocular chemical injuries often cause uveal inflammation, upregulation of TNF-alpha at the limbus, and subsequent limbal stem cell (LSC) damage. In this study, we investigate the protective role of TNF-alpha suppression in LSC survival. Methods: Corneal alkali injuries were performed using NaOH as previously described by our group. Anterior chamber pH elevation in the absence of corneal alkali exposure was achieved by cannulation. A CX3CR1(+/EGFP)::CCR2(+/RFP) bone marrow chimera was used to study the role of innate immune cells in LSC damage, which was assessed by TUNEL assay, ABCB5, cytokeratin 12 and 13 staining, flow cytometry, in situ hybridization, and qPCR. Corneal neovascularization and conjunctivalization were evaluated by light microscopy. Intraperitoneal injection of 6.25 mg/kg infliximab was administered after irrigation. A TNFR1/2 knockout mouse was used to confirm the findings by a second method. Results: Systemic administration of 6.25 mg/kg infliximab suppressed uveal inflammation after anterior chamber pH elevation or corneal alkali injury and led to reduction of TNF-alpha secreting CCR2(+) and CX3CR1(+) monocytes in the basal limbal tissue. In turn, this led to LSC survival (P < 0.01) and allowed reestablishment of K12(+) epithelium (P < 0.05) on the injured cornea. Moreover, it led to less corneal neovascularization, conjunctivalization, and scarring, as compared with untreated animals. The protective effect of TNF-alpha suppression was confirmed in TNFR1/2 knockout mice. Conclusions: Prompt systemic administration of TNF-alpha inhibitor prevents LSC deficiency and facilitates corneal reepithelialization after alkali burn. TNF-alpha suppression may benefit the outcomes of other ocular injuries that cause LSC deficiency.

关键词： HBV reactivation   rheumatologic patients   TNF-alpha inhibitor potency  

摘要： BackgroundRheumatologic patients who test positive for hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) are at risk of HBV reactivation when treated with TNF-alpha inhibitors. The effect of TNF-alpha inhibitor potency on this risk remains unclear, despite guidelines advising potency-based risk stratification. This study examines how TNF-alpha inhibitor potency influences the risk of HBV *** January 2008 to June 2023, 711 new TNF-alpha inhibitor users with rheumatic diseases were identified, including 39 HBsAg+ patients with antiviral prophylaxis, 72 HBsAg+ patients without antiviral prophylaxis, and 600 HBsAg-/HBcAb+ patients without prophylaxis. A Cox proportional hazards model assessed factors associated with HBV *** 2526 person-years of follow-up, HBsAg+ patients without antiviral prophylaxis had the highest HBV reactivation rate at 104.1 per 1000 person-years, followed by HBsAg-/HBcAb+ patients at 12.9, and HBsAg+ patients with antiviral prophylaxis at 12.6 per 1000 person-years. Multivariate Cox regression revealed that high-potency TNF-alpha inhibitors significantly increased HBV reactivation risk in HBsAg+ patients without antiviral prophylaxis (aHR 3.24, 95% CI: 1.09-9.67, p = 0.04). Adalimumab had a higher reactivation risk compared to etanercept (aHR 3.23, 95% CI: 1.02-10.17, p = 0.04), followed by golimumab (aHR 3.27, 95% CI: 0.91-11.64, p = 0.07). For HBsAg-/HBcAb+ patients, TNF-alpha inhibitor potency did not significantly impact HBV reactivation risk;instead, age over 65 was the only significant risk factor (aHR 3.37, 95% CI: 1.30-8.70, p = 0.01).ConclusionHigh-potency TNF-alpha inhibitors significantly increase HBV reactivation risk in HBsAg+ patients, while HBsAg-/HBcAb+ patients have a uniformly low risk across all inhibitors.

关键词： Horse   Sarcoid   MHC   KLRA   Association  

摘要： Although the Major Histocompatibility Complex (MHC) has been repeatedly associated with susceptibility to equine sarcoid, a disease associated with bovine papillomavirus infection, the role of the MHC in the mechanisms of the disease is not fully understood. The objectives of our work were to analyze associations between polymorphic markers of the MHC genomic subregions and of the Natural Killer Complex (NKC) genomic region and the presence of sarcoid in Arabian horses. Microsatellite loci located in the MHC class I, II and III subregions and two MHC class II genes (DRA, DQA1), along with a set of NKC (KLRA, CLEC subregions) microsatelllite markers were genotyped. Fifteen microsatellites of the standard parentage kit, located outside the MHC and NKC regions, were tested as controls. Standard chi-square and Fisher tests with Bonferroni corrections were used for association analyses. Significant associations of MHC class II and MHC class I_KLRA polymorphic markers with the presence of clinical sarcoid were observed. These findings are consistent with biological theory and indicate a role of MHC class I, class II and KLRA molecules in adaptive as well as in innate immune responses to equine sarcoid. Although limited to Arabian horses, these data point to an as yet unadressed hypothesis regarding the possible roles of NK cells in the pathogenesis of equine sarcoid.

关键词： HLA polymorphism   HLA‐B gene   alleles   haplotypes   histocompatibility testing  

摘要： HLA-B*27:277 differs from HLA-B*27:05:02:05 by a single substitution in exon 6.

关键词： Beh & ccedil   et's disease   clinical manifestations   gender differences   genetics   HLA-B51  

摘要： HLA-B51 is well-established as a genetic risk factor for the development of Beh & ccedil;et's disease (BD), and its association with certain clinical manifestations has been documented. However, there is a lack of comprehensive research examining its role in the overall symptom completeness and full clinical expression of the disease. We performed a retrospective review of medical records from 1203 patients treated at a tertiary hospital between June 2012 and June 2017. Data regarding HLA-B51 status and clinical conditions were extracted, and patients were classified according to the "Revised Japanese Diagnostic Criteria for Beh & ccedil;et's disease (1987)", resulting in 878 patients diagnosed with complete (n = 250) and incomplete (n = 628) BD. Among these patients, 400 (45.6%) were tested positive for HLA-B51, with the positivity rate progressively increasing with the severity of symptoms. Male patients exhibited a higher likelihood of HLA-B51 positivity (61.9%) and a greater prevalence of skin and ocular symptoms, while female patients showed a higher incidence of erythema nodosum (42.2%) and genital ulcers (91.0%). Notably, a positive correlation was observed between skin lesions and genital ulcers, whereas ocular symptoms demonstrated a negative correlation with both skin and genital manifestations. This study underscores the significant impact of HLA-B51 positivity on the clinical presentation of BD. Insights gained from this research can enhance our understanding of genetic influences on symptom expression, ultimately leading to diagnostic and therapeutic approaches for patients with the disease.

关键词： HLA‐DPB1*19:01:02   next‐generation sequencing   novel allele  

摘要： HLA-DPB1*19:01:02 differs from HLA-DPB1*19:01:01 by a single nucleotide substitution at position 735 C>T.

摘要： Regulations, accreditation standards, and professional guidance require laboratories to use reference materials for assay development, validation, quality control, and proficiency testing of clinical genetic tests. There are, however, few publicly available reference materials for most genetic tests. To address this issue, the CDC's Genetic Testing Reference Material Program (GeT-RM), the Coriell Institute for Medical Research, and the genetic testing community have conducted 19 studies, including nine for pharmacogenetic (PGx) and human leukocyte antigen (HLA) testing, to generate characterized, renewable, and publicly available DNA samples for use as reference materials. Because new PGx alleles are frequently identified, and allele designations change over time, many samples were reanalyzed for the same gene(s) in subsequent GeT-RM studies. These studies used more comprehensive and sensitive methods and panels that examined additional single-nucleotide variants and/or star alleles to expand and update the consensus genotypes. Up-to-date information is available in two newly established resources: the GeT-RM Consolidated PGx and HLA Table and the GeT-RM PGx Search Tool. These resources contain all available PGx and HLA genotypes for 363 publicly available samples characterized during nine GeT-RM PGx or HLA studies for 34 genes/loci in a consolidated and searchable format. (J Mol Diagn 2025, 27: 457-464;https://***/10.1016/***.2025.02.008)

关键词： Bifidobacterium animalis subsp. lactis A6   immunoglobulin E   interleukin-13   perennial allergic rhinitis  

摘要： ObjectivesThe evidence regarding the efficacy of probiotics in improving allergic rhinitis (AR) remains inconsistent. This study aimed to evaluate the potential effects of Bifidobacterium animalis subsp. lactis A6 (A6) on perennial *** randomized, double-blind, placebo-controlled trial was conducted involving 70 adults with perennial AR receiving either probiotic (A6, 5 x 1010 CFU/sachet per day) or placebo intervention for 8 weeks. Nasal symptoms and quality of life (QoL) were recorded using total nasal symptom scores (TNSS) and the rhinitis quality of life questionnaire (RQLQ). Blood eosinophil count, total immunoglobulin E (IgE), allergen-specific IgE, and immunological parameters were also *** 8 weeks of intervention, the probiotic group showed a statistically significant greater reduction in TNSS total score compared with the placebo group [-3.11 (3.53) vs. -1.29 (3.34), p = 0.029, Cohen's d = 0.68]. Similar results were noted for serum total IgE and interleukin-13 (IL-13). Comparable findings were seen for RQLQ score only at week 4 but not at week *** conclusion, A6 could statistically significantly alleviate rhinitis symptoms and improve QoL in adults with perennial AR. The effect size, as measured by Cohen's d, suggests that A6 may provide clinically meaningful benefits for AR patients to a certain *** Trial *** Identifier no. ChiCTR2200064158.

关键词： HLA-A*24:642   NGS   novel allele  

摘要： HLA-A*24:642 differs from HLA-A*24:02:01:01 by a single nucleotide substitution at position 76 T>C in exon 2.

关键词： Rib fractures   inflammation   acute lung injury   acute kidney injury   IL2Ra  

摘要： BACKGROUNDRib fractures compromise approximately 40% of all fractures in the United States. Despite their prevalence, the relationship between rib fractures, solid organ injuries, and immune responses remains poorly understood. This exploratory study investigates the immunological profile associated with pulmonary and renal complications in rib fracture patients using data from our Surgical Critical Care Initiative Clinical Data Repository. The aim is to correlate distinct cytokine/chemokine profiles with high-energy rib fracture patterns, such as first rib fracture, and associated complications, potentially providing predictive biomarkers for patient outcomes. METHODSClinical and demographic data on patients with rib fractures were extracted from Surgical Critical Care Initiative Clinical Data Repository. Patients were categorized based on the presence or absence of complications. A comprehensive panel of 46 inflammation and tissue repair biomarkers was measured using the Meso Scale Discovery platforms. Principal component analysis was used to reduce the dimensionality of the cytokine data. Statistical and machine learning models assessed the association between biomarker patterns, rib fracture localization, and complications. Logistic regression models with high discriminative performance were developed for first rib fractures (high energy transfer), lung injury, and pneumonia. RESULTSAmong 150 rib fracture patients, 73 had complications. Cytokine analysis revealed two distinct clusters: Cluster 1, associated with pro-inflammatory responses and tissue repair, and Cluster 2, linked with anti-inflammatory responses, angiogenesis, and immunometabolism. Predictive models demonstrated strong validity (area under the curve, >0.90) and identified key variables such as the cytokine IL2Ra, significantly associated with acute kidney injury, acute lung injury, and pulmonary complications post-rib fractures, particularly first rib fractures. CONCLUSIONIL2Ra release is signifi