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关键词： COVID-19   cryopreservation   engraftment   graft versus host disease   hematopoietic stem cell transplantation  

摘要： The coronavirus disease 2019 (COVID-19) pandemic created major challenges for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Scientific societies and authorities recommended cryopreserving grafts before starting conditioning regimens, despite limited data on the clinical impact. The Italian Group for Bone Marrow Transplantation (GITMO) conducted a registry-based study involving 3492 patients who underwent allo-HSCT between March 2018 and September 2021. The cryopreserved cohort (n = 976) included patients who received cryopreserved grafts during the pandemic and was compared to the historical cohort (n = 2516). Graft cryopreservation was associated with a lower day 30 incidence of neutrophil and platelet engraftment (adjusted sHR = 0.8 and 0.7, p = 0.031 and p < 0.001, respectively) and delayed hematopoietic recovery. However, primary graft failure rates at day +30 were similar in the cryo and historical cohort (4% vs. 5%, respectively;p = 0.337), also after adjustment (RR = 1.19, p = 0.518). Day 100 incidence of grade II-IV acute GVHD was comparable between the two groups (adjusted sHR = 1.2, p = 0.194). Regarding chronic GVHD incidence, we found that it was higher in patients aged < 18 years in the cryo group (adjusted sHR = 3.9, p = 0.002), but lower in those aged 18-55 years (adjusted sHR = 0.7, p = 0.008). Cumulative incidence of relapse did not differ between historical and cryo cohort (adjusted sHR 1.0. p = 0.943), as well as non-relapse mortality (adjusted sHR 1.1, p = 0.196) and relapse-free survival (adjusted sHR = 1.1, p = 0.197). However, a shorter overall survival was observed in the cryopreserved group (adjusted HR = 1.2, p = 0.038). Transplant centers should carefully balance the benefits and drawbacks of cryopreservation in allo-HSCT.

关键词： NLR   PHR   PLR   Psoriasis vulgaris   SII  

摘要： Background and objective IL-17 and IL-23 inhibitors are widely used as biological agents in patients with psoriasis vulgaris to suppress inflammation and reduce disease severity. This study aimed to examine changes in inflammatory parameters, including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic inflammation index (SII), platelet/hemoglobin ratio (PHR), and red cell distribution width/platelet ratio (RPR), as well as the Psoriasis Area and Severity Index (PASI), in psoriasis patients receiving biological therapy (IL-17 and IL-23 inhibitors). Materials and methods This retrospective study included 110 patients with psoriasis vulgaris treated with IL-23 (risankizumab, guselkumab or IL-17 inhibitors ( secukinumab, and ixekizumab). Disease severity was assessed using the PASI score. Hematological parameters (NLR, PLR, SII, PHR, and RPR) and PASI values of the patients were recorded and analyzed at baseline (month 0) and during treatment (month 6). Results A significant decrease was observed in NLR, SII, and PHR values during treatment. NLR decreased significantly from 2.43 +/- 1.25 at baseline to 2.12 +/- 0.81 at month 6 (p = 0.002). Both IL-17 and IL-23 groups significantly reduced NLR (p = 0.044, p = 0.029, respectively). SII decreased significantly from 695 +/- 390 at baseline to 588 +/- 288 at month 6 (p = 0.002). Both groups significantly reduced SII levels (p = 0.044, p = 0.018, respectively).PHR decreased significantly from 19.8 +/- 6.60 at baseline to 19.2 +/- 6.58 at month 6 (p = 0.033).PASI score significantly decreased during treatment (p < 0.001). Conclusion The significant reduction in NLR and SII levels in both the IL-17 and IL-23 groups suggests that these markers may be used together rather than separately in treatment follow-up. The significant decrease in PHR levels may indicate that IL-17 and IL-23 inhibitors contribute to reducing cardiovascular disease risk in patients with psoriasis vulgaris and promote a favorable

关键词： IFN-γ   helminth   intestinal immunity   microbiota   neutrophils   stroma  

摘要： IFN-γ function during a type-2 helminth infection remains enigmatic. Westfall et al. found an unexpected role for IFN-γ in limiting tissue damage during intestinal infection by Heligmosomoides polygyrus bakeri (Hpb). IFN-γ produced by CD8+ T cells stimulates stromal cells directly to recruit neutrophils, where they prevent tissue damage caused by the worms.

关键词： Ankylosing Spondylitis   Arthritogenic Peptides   HLA-B*14   HLA-B*27   Mass Spectrometry   Peptide Repertoires   cross-reactivity  

摘要： The human major histocompatibility complex class I (HLA-I) gene HLA-B*27 is the main risk factor for the rheumatic disease ankylosing spondylitis (AS) through an unknown mechanism. However, in African populations, where B*27 is rare, the B*14:03 allotype is strongly associated with AS, while B*14:02, which only differs from B*14:03 at one residue (L156R), is not associated with the disease. Here, we have used large-scale mass spectrometry-based peptide sequencing to analyze the peptidomes of HLA-B*14:03, HLA-B*14:02, and HLA-B*27:05, obtaining more than 2000 peptide ligands for each molecule. Remarkably, we found 1011 ligands shared by the AS-associated HLA-B*27:05 and -B*14:03 alleles and not by the non-AS-associated B*14:02 allele. Surprisingly, although B*14:03 and B*27:05 differ by 15 amino acids in their peptide binding domain, they show a large overlap of their ligands (64 and 43% respectively), while B*14:03 and B*14:02, which differ by only one residue, show a lower degree of overlap (33-35%). B*14:03 peptide repertoire most resembles that of B*27:05 at the P1, P2, and P5 positions of the peptides, and differs most at the C-terminal position, where B*14:03 is more restrictive than B*27:05. We have modeled how the change at residue 156 of the two B*14 alleles could have a long-range indirect effect on residues P1, P2, and P5 of the peptide ligands, explaining the different amino acid distribution observed between the two B*14 subtypes at those positions. Most of the 1011 specific ligands of B*14:03 and B*27:05 presented R/K/A/G at P1, R at P2, and L/F at the C-terminal position. Of these 1,011 peptides, 10 have been previously identified as presented by the three HLA-B*27 subtypes most strongly associated with AS and are absent in non-associated subtypes, while four peptides from the HLA 169-181 region-previously implicated in the autoimmune pathogenesis of AS-were also identified, suggesting that differential peptide binding may influence disease development

关键词： DNA methylation   IL6   Methotrexate   Propolis   Epigenetic   Leukemia   COVID-19   Epidrugs  

摘要： BackgroundThe natural active ingredient propolis, which is used to support the treatment of inflammatory diseases, and the drug methotrexate (MTX), which is used to treat tumor diseases, have already shown that they are able to change the DNA methylation *** aim of the study was to evaluate the ability of propolis oral spray and intravenous methotrexate to modulate the DNA methylation profile of the interleukin-6 (IL6) gene, which encodes an inflammatory cytokine that is important in both inflammatory and tumor *** propolis intervention was tested in adults affected by COVID-19 (n = 114) and the methotrexate intervention was tested in children and adolescents with leukemia (n = 64). DNA methylation in the IL6 gene promoter was analyzed using the methylation-specific PCR (MSP) technique using DNA extracted from oral mucosa or *** fully methylated profile in blood cells of adults with COVID-19 was observed in 100% of the samples both before and after the propolis intervention. The methylated profile was also observed in buccal cells from pediatric patients with leukemia in 100% of the samples regardless of MTX *** is concluded that the methylated profile in the IL6 gene promoter is a common profile for adult blood cells and pediatric oral cells and is not modulated by the use of propolis or methotrexate.

关键词： Systemic sclerosis   Interleukin 40   Biomarkers  

摘要： BackgroundInterleukin 40 (IL-40) is a cytokine implicated in malignancies and rheumatic disorders. Its association with fibrotic mediators has been previously described. Since inflammation and fibrosis are hallmarks of systemic sclerosis (SSc), we aimed to analyze the role of IL-40 in SSc. MethodsIL-40 levels were analyzed in the serum of 90 SSc patients and 75 healthy controls (HCs). IL-40 expression in dermal biopsies from 5 SSc patients and 5 HCs was assessed via immunohistochemistry. IL-40 was analyzed in 39 SSc patients with interstitial lung disease treated with cyclophosphamide (CPA) and in 24 SSc patients with active progressive disease treated with rituximab (RTX). SSc activity was assessed by the European Scleroderma Study Group (ESSG) index. The effect of recombinant IL-40 on peripheral blood mononuclear cells (PBMCs) from 10 SSc patients was determined in vitro. IL-40 was analyzed in 24 individuals at risk of developing SSc (VEDOSS), who were categorized as progressors (n = 11) and nonprogressors (n = 13). ResultsIL-40 expression was elevated in the skin of SSc patients compared to HCs, particularly in fibroblasts and immune infiltrates. Serum IL-40 was increased in SSc compared to HCs (p < 0.0001) and was associated with ESSG (r = 0.372, p = 0.0005) and gastrointestinal involvement (p < 0.05). IL-40 correlated with serum IL-8 (r = 0.270, p = 0.019) and TGF-beta 1 (r = 0.301, p = 0.024) levels. In the CPA and RTX cohort, no significant changes in the serum IL-40 were observed upon treatment. Baseline and changes in IL-40 levels were associated with changes in several clinical parameters. IL-40 was elevated in patients at risk of SSc compared to HCs (p = 0.0003). No significant changes were observed in progressors vs. nonprogressors;however, IL-40 was associated with capillaroscopy findings (p < 0.05). IL-40 induced the upregulation of IL-6 (p = 0.002), MCP-1 (p = 0.002) and IL-10 (p = 0.002) in PBMCs from SSc patients in vitro. ConclusionsIL-40 was upreg

关键词： Lung carcinoma   Molecular pathogenesis   HLA-A   HLA-B   HLA-DR  

摘要： According to GLOBOCAN 2022 estimates, lung cancer is the leading cause of cancer morbidity and mortality in 2022. 5 year survival rate is dismal for the disease, despite advances in therapeutic modalities. Current research into lung cancer therapy is largely focused on molecular advancements. Our study was focused on finding association between the HLA expression in lung carcinoma patients, in northern region of India. It contributes data for basic molecular understanding of pathogenesis in lung cancer patients. This study was conducted in the Department of Pathology and Department of Pulmonary critical care and sleep medicine, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi. A total of 35 lung cancer cases and 35 healthy controls were taken over a period of 18 months and results were compared. In our study the mean age of presentation for lung carcinoma patients was 52.29 years HLA-A11 (p value = 0.028) and HLA-B51 (p value = 0.035), were under expressed in the patients as compared to control group, and HLA-DRB1*15 (p value = 0.037) was over expressed in the patients as compared to control group. However, no statistically significant result was seen in co-relation to the clinical staging. The results of this small sample study provide data for a completely new population and might help to guide in understanding the role of HLA in lung carcinoma patients for future studies.

关键词： syphilis   serofast state   IFN-gamma   polymorphism   SNP   +874 T/A   +2109 A/G  

摘要： Background: In approximately 20% of patients with early syphilis, the classical serological response pattern is absent following treatment. They experience a serofast state, which manifests as less than a 4-fold decline in non-treponemal titres, without any clinical signs of treatment failure or reinfection. The effectiveness of the immune defense against T. pallidum, as well as its potential failure and the occurrence of the serofast state, depends on the Th1 cellular response, including cytokines such as IFN-gamma. The aim of this prospective observational study was to investigate the impact of IFN-gamma gene polymorphisms on the occurrence of the serofast state. Materials and methods: A cohort of 97 patients with early syphilis (73.2% secondary syphilis, 26.8% early latent syphilis) and 50 healthy volunteers were enrolled. Two single nucleotide polymorphisms (SNPs) in the IFN-gamma gene promoter region, +874 T>A (rs2430561) and +2109 A>G (rs1861494), were analyzed. Serum IFN-gamma levels were measured at baseline, prior to treatment. Patients were stratified into serofast (n=18) and serologically cured (n=79) groups. Results: Serofast patients exhibited significantly lower baseline serum IFN-gamma levels compared to the serologically cured group (p=0.01). All healthy subjects had IFN-gamma levels below the detection limit. Analysis of IFN-gamma gene polymorphisms revealed a significant association with treatment outcomes. The +874 AA and +2109 GG genotypes, associated with low IFN-gamma production, were significantly more frequent in serofast patients (p=0.0004 and p=0.002, respectively), with odds ratios (OR) of 7.1 (95% CI: 2.2-23.2) and 5.5 (95% CI: 1.8-17.3), respectively. Additionally, carriers of the +874A/+2109G haplotype were significantly more likely to remain serofast (OR 4.4, p=0.01). Conversely, the +874 TT and +2109 AA genotypes, associated with high IFN-gamma production, were significantly linked to serological cure (OR 4.4, p=0.03;OR 4.4, p=0.01).

关键词： Hypobaric hypoxia   HAPE   NKT cells   IL-10   curcumin  

摘要： Background: There are environment-dependent pro-inflammatory and anti-inflammatory pathways during exposure to high altitudes. Although inhibiting the inflammatory pathway can alleviate high altitude pulmonary edema (HAPE), it is currently unclear whether inflammation is the cause of edema or the result of edema in HAPE-afflicted patients. Natural killer T (NKT) cells are a subset of T cells that play an important role in a variety of lung diseases. However, its specific role in HAPE remains unclear. Methods: HAPE rat model was established under hypobaric hypoxia condition. To investigate the role of NKT cells in HAPE, phenotypic and functional changes of NKT cells and their subpopulations were analyzed by flow cytometry. To further investigate the effect of TNF-alpha on NKT cells, rats were given intraperitoneal injection of TNF-alpha, and then, NKT cells were characterized by flow cytometry. Subsequently, the levels of TNF-alpha in the lungs and spleens of rats were detected by ELISA, and HAPE rats were treated with curcumin. Results: Compared with normal control, the ratio of TNF-alpha and IL-10 secreted by lung NKT cells was decreased in HAPE rats induced by hypoxia. Further analysis showed that the mean fluorescence intensity (MFI) of TNF-alpha in NKT cells did not change significantly, but the MFI of IL-10 increased significantly. Moreover, the MFI of IL-10 produced by TNF-alpha-treated rat lung NKT cells was higher, which was completely different from spleen NKT cells. ELISA experiments indicated that TNF-alpha was enriched in the lung tissue of rats regardless of hypoxia, and the level of TNF-alpha in lung tissue was upregulated after hypoxia. Furthermore, when HAPE rats were treated with curcumin, the MFI of IL-10 in the NKT cell subsets decreased. Conclusions: NKT cells produce high levels of IL-10, which inhibits the production of lung inflammation in HAPE rats. With the increase of TNF-alpha level, the inhibitory effect of lung NKT cells on inflammation