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关键词： Fibrosis   IFN alpha   Mortality   Systemic sclerosis   Type I IFN  

关键词： acute rejection   amino acid mismatches   EMMA   Eplet   HLA compatibility   HLA mismatch   HLA serotypes   molecular mismatches   PIRCHE  

摘要： The purpose of this single-center case-control study was to investigate the association between HLA serotype mismatch (MM), compared to other HLA MM modalities, and the occurrence of acute rejection (AR) within the first year after deceased donor kidney transplantation. The study included 198 transplants in 99 pairs of recipients of kidneys from the same donor, where one recipient experienced AR and the other survived the first year without AR. Donors and recipients were typed with NGS for 11 HLA loci at high resolution. HLA MM categories included allele groups, alleles, serotypes, amino acids, EMMA, eplet and PIRCHE-II. Additionally, we investigated Cytomegalovirus LIL peptide (CMV LIL) MM. Recipients with AR presented higher frequencies of pre-transplant HLA-ABDR DSA (20.2% vs. 6.1%, p = 0.005) and CMV LIL MM (24.2% vs. 10.1%, p = 0.01). Univariate and multivariate Cox proportional hazards regression for matched-pair analyses were used to test the association between HLA MM and AR. Univariate analyses indicated significant association with DRB1 ST, HLA-DQB1 AG, HLA-DQB1 AL, EMMA C, EMMA DQB1, Eplet ABC and Eplet DQ MM. Different models were tested in multivariate analyses, all including pre-transplant HLA-ABDR DSA and CMV LIL MM. The models were compared using the Akaike Information Criterion (AIC). The best estimate for AR prediction (AIC = 97.6) was the model that included pre-transplant HLA-ABDR DSA (HR = 11.97;p = 0.003), CMV LIL MM (HR = 367.2;p < 0.001), HLA-DRB1 serotype MM (9.65;p = 0.002) and HLA-DQB1 allele MM (HR = 3.54;p = 0.033). In conclusion, this original report demonstrates an association between the HLA-DRB1 serotype MM and AR, highlighting that serotypes are clinically relevant.

关键词： HLA-C*08:296   new allele   NGS   relative  

摘要： HLA-C*08:296 differs from HLA-C*08:02:01:01 by two nucleotide changes, one in an exon and one in an intron.

关键词： L-17 inhibition   Immunomodulation   Personalized therapy   Secukinumab   Type 1 diabetes mellitus  

摘要： We report the case of a 30-year-old male with psoriatic arthritis treated with secukinumab (anti-IL-17A) who developed new-onset type 1 diabetes mellitus (T1DM). During follow-up, a consistent reduction in insulin requirements and glycemic variability was observed in the two weeks following each dose of secukinumab. This suggests a possible immunomodulatory effect of IL-17 inhibition on beta-cell function and glycemic control. To our knowledge, this is the first report describing clinical benefits of secukinumab in the early stages of T1DM, highlighting its potential as a therapeutic tool in modulating autoimmune processes involved in disease progression.

关键词： spondyloarthritis   IBD   TNF  

摘要： Objectives: Gut and joint disease commonly co-occur in SpA. Up to 50% of patients with SpA show signs of subclinical gut inflammation, of which 10% develops IBD. However, the mechanisms underlying this gut-joint axis are still unclear. Here we investigated the hypothesis that restricted expression of a pro-inflammatory cytokine in the intestine may trigger the onset of combined gut and joint inflammation. Methods: Intestinal expression of human TNF (hTNF) was achieved by driving hTNF gene expression using the rat FAPB2 promoter, creating a new animal model, TNFgut mice, that expresses hTNF in the proximal intestinal tract. Intestinal-specific TNFgut mice were examined for pathological changes in the intestine and extra-intestinal tissues by means of histology, reverse transcription PCR (RT-PCR) and flow cytometry, along with 16S sequencing on stools. Results: Local expression of hTNF in the epithelium of the small intestine induces a pro-inflammatory state of the proximal intestinal tract, with epithelial alterations and induction of members of the S100 family, as well as local upregulation of Th17 and Treg, but no obvious signs of dysbiosis. Curiously, TNFgut mice develop sacroiliitis (P <0.05) in addition to small bowel inflammation (P <0.05). However, no signs of peripheral arthritis or enthesitis could be documented. Conclusion: Intestinal expression of hTNF is sufficient to initiate a pro-inflammatory cascade culminating in small bowel inflammation and sacroiliitis. Thus, gut-derived cytokines are sufficient to induce SpA.

关键词： HLA   Novel HLA alleles   NGS  

摘要： HLA compatibility between patients and donors is a determining factor for the success of stem cell and solid organ transplantations. However, finding suitable donors remains challenging due to the highly polymorphic nature of HLA genes. Here we are describing 16 novel HLA-A,-B,-C and-DRB1 alleles identified over the period of 2 years. Fourteen differed from their closest reference allele sequence by single nucleotide substitutions detected in the coding regions and 13 contained polymorphism outside antigen recognition domains (exons 2 and 3 in class I and exon 2 in HLA class II). Two novel alleles, a non-sense substitution and a deletion of 2 bp resulted in two null alleles, while a substitution in a splice site resulted in an allele with questionable expression status. In HLA matching procedures, particularly in donor selection, it is important to determine alternatively expressed HLA alleles. Thirteen additional HLA-A,-B,-C and-DRB1 alleles detected as novel at the time of testing were already reported by other laboratories by the time of submission.

关键词： allele   genotype   haplotype   HLA   HLA-DM   HLA-DO   MHC   novel allele  

摘要： HLA-DMA, -DMB, -DOA and -DOB are non-classical HLA Class II genes that play a crucial role in the selection of highly stable HLA Class II/peptide complexes on antigen-presenting cells. Although the genes were initially thought to have a limited diversity with less than 13 alleles per gene documented in the IPD-IMGT/HLA Database in 2022, recent studies suggest a potential impact of certain alleles on the outcome of hematopoietic cell transplantation. To gain a deeper understanding of allelic diversity, we sequenced HLA-DMA, -DMB, -DOA and -DOB of 1880 potential stem cell donors from Germany, Poland, Great Britain and Chile, achieving full-gene resolution. Remarkably, we identified 3968 previously undescribed sequences, including 28 distinct novel proteins. The observed allele frequencies were consistent across all studied populations with one dominating protein for each gene: HLA-DMA*01:01 (> 77%), HLA-DMB*01:01 (> 63%), HLA-DOA*01:01 (> 97%) and HLA-DOB*01:01 (> 77%). Notably, a much higher diversity was observed in full-genomic resolution. Finally, we submitted 51 distinct novel sequences for HLA-DMA, 58 for HLA-DMB, 80 for HLA-DOA and 47 for HLA-DOB to the IPD-IMGT/HLA Database. This comprehensive reference database update will not only simplify future genotyping of HLA-DMA, -DMB, -DOA and -DOB but will hopefully also enhance our understanding of the complex process of peptide selection and loading to the HLA Class II proteins.

关键词： MSC   Chemokine   TSG-6  

关键词： Interleukin 6   Lung function   Mycoplasma pneumoniae pneumonia   Procalcitonin   severity   Prognostic predictions  

摘要： Objective: To explore the correlation of interleukin 6 (IL-6) and procalcitonin (PCT) with severity of Mycoplasma pneumoniae pneumonia (MPP) in children and their prognostic value. Methods: One hundred twenty children with MPP and 100 healthy children who underwent physical examination at the Clinical Laboratory Department of Nantong University Maternal and Child Health Hospital from November 2023 to December 2023 were selected as the study subjects, and were divided into the experimental group and the control group. The experimental group was divided into mild MPP group (n=70 ) and severe MPP group (n=50 ) according to the severity of the disease. According to the condition after one course of treatment, separated MPP children into good prognosis group (n=96) and poor prognosis group (n=24). The IL-6 and PCT levels of the experimental/control group before treatment and the good/bad prognosis group after treatment were compared, respectively. The lung function of children with MPP before and after treatment was also examined, and the changes of respiratory rate (RR), tidal volume (VT), expiratory time (Te), peak time (TPTEF), and peak volume (VPTEF) were observed. The correlation between pulmonary function and IL-6, PCT in MPP children was analyzed by Pearson analysis. Receiver operation curve was adopted to analyze the predictive value of IL-6, PCT for poor prognosis. Results: IL-6 and PCT were increased in the severe MPP group compared to the mild MPP group (P<0.001) and tended to decrease in the good prognosis group compared to the poor prognosis group (P<0.001). Fifty-nine of the 70 cases in the good prognosis group were patients with mild MPP, suggesting that patients with mild MPP have a better prognosis. The results of respiratory function showed an increase in RR (P<0.001) and a decrease in VT (P=0.007), TPTEF/Te (P<0.001), VPTEF/VT (P<0.001) in the severe MPP group compared to the mild MPP group. The results of correlation analysis revealed that IL-6, PCT w

关键词： Rosacea   STAT3   Skin inflammation   IL-36G   Pogostone  

摘要： Background: Rosacea is an inflammatory skin disorder characterized by the release of inflammatory mediators from keratinocytes, which are thought to play a crucial role in its pathogenesis. Despite an incidence of approximately 5.5%, rosacea is associated with a poor quality of life. However, as the pathogenesis of rosacea remains enigmatic, treatment options are limited. Objectives: To investigate the pathogenesis of rosacea and explore new therapeutic strategies. Methods: Transcriptome data from rosacea patients combined with immunohistochemical staining were used to investigate the activation of STAT3 in rosacea. The role of STAT3 activation in rosacea was subsequently explored by inhibiting STAT3 activation both in vivo and in vitro. The key molecules downstream of STAT3 activation were identified through data analysis and experiments. Dual-luciferase assay and ChIP-qPCR analysis were used to validate the direct binding of STAT3 to the IL-36G promoter. DARTS, in combination with experimental screening, was employed to identify effective drugs targeting STAT3 for rosacea treatment. Results: STAT3 signaling was hyperactivated in rosacea and served as a promoter of the keratinocytedriven inflammatory response. Mechanistically, activated STAT3 directly bind to the IL-36G promoter region to amplify downstream inflammatory signals by promoting IL-36G transcription, and treatment with a neutralizing antibody (a-IL36c) could mitigate rosacea-like inflammation. Notably, a natural plant extract (pogostone), which can interact with STAT3 directly to inhibit its activation and affect the STAT3/ IL36G signaling pathway, was screened as a promising topical medication for rosacea treatment. Conclusions: Our study revealed a pivotal role for STAT3/IL36G signaling in the development of rosacea, suggesting that targeting this pathway might be a potential strategy for rosacea treatment. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open