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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： 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： 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： 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