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关键词： HLA-DPA1*01:238Q   next generation sequencing   novel HLA allele   null allele   third generation sequencing  

摘要： The novel HLA allele HLA-DPA1*01:238Q, detected during routine HLA typing, is most likely not expressed.

关键词： Tuberculosis   Interleukin-12   Interferon-Gamma   Polymorphism   PCR-RFLP   Sudan  

摘要： BackgroundTuberculosis (TB) is a top infectious disease killer worldwide. The susceptibility to infectious diseases, including tuberculosis, has been linked to several cytokine gene polymorphisms. MethodA case-control study was conducted at Abu Anja Chest Hospital, Omdurman, Khartoum state, using PCR-RFLP in 200 Sudanese patients with pulmonary tuberculosis and 200 healthy controls between February 2018 and February 2021. Data analysis was done using the IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). ResultThe mutant and heterozygous genotypes of IL-12+16974 A/C polymorphism were associated with an almost four-fold [P-value <0.001 OR= 3.703(2.243- 6.115), 95% CI] increased risk of TB in the Sudanese population. No statistically significant differences were found in the genotype and allele frequencies of the IFN-gamma+874T/A gene between patients and controls. ConclusionThese findings suggest, for the first time in Sudan, the significant risk of TB in people carrying the mutant and heterozygous genotypes of IL-12+16974 A/C genes.

关键词： desmoplakin   interleukin-1   myopericarditis   BNP   brain natriuretic peptide   DSP   hs-TnI   high-sensitivity troponin I   IL   interleukin   LVEF   left ventricular ejection fraction  

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关键词： IL-15   IFN gamma   macrophages   human skin   inflammation   skin diseases   psoriasis   atopic dermatitis  

摘要： Interleukin (IL)-15 is primarily known as a pro-inflammatory and anti-apoptotic cytokine, which stimulates the proliferation and survival of key immunocytes, including macrophages (MACs). Yet, it remains unclear how IL-15 specifically impacts MACs in intact human skin, particularly immunoinhibitory, IL-10-producing/secreting M2 MACs (CD206+IL-10+). In the current pilot study, we explored this in organ-cultured healthy human eyelid skin in the presence of IFN gamma (100 IU/mL) to mimic a pro-inflammatory signaling milieu found in several chronic immunodermatoses. Quantitative immunohistomorphometry showed that IFN gamma significantly reduced the number of CD68+MACs, M2 CD206+MACs, and immunoinhibitory CD206+IL-10+MACs. Moreover, co-administering recombinant human (rh) IL-15 after inducing inflammation by IFN gamma largely reversed the IFN gamma-induced decline in MAC populations. To investigate if this was mediated via the private IL-15 receptor alpha (IL-15R alpha), we successfully silenced IL-15R alpha in human skin ex vivo. Indeed, co-administration of IL-15R alpha siRNA abrogated the rhIL-15 protection of M2 CD206+MACs against IFN gamma, but not of the CD206+IL-10+MAC subpopulation. These pilot data suggest that IL-15 maintains immunoinhibitory M2 CD206+IL-10+MACs in human skin under IFN gamma-dominated inflammatory conditions. Therefore, it deserves to be explored whether IL-15 or IL-15R alpha agonists can exert therapeutic benefit in chronic inflammatory dermatoses by preserving the intracutaneous pool of anti-inflammatory dermal M2 MACs.

关键词： diffuse large B-cell lymphoma   central nervous system   interleukin-10   interleukin-6   prognosis  

摘要： Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and carries a poor prognosis when it involves the central nervous system (CNS), a condition known as secondary CNS lymphoma (SCNSL). Although the CNS International Prognostic Index (CNS-IPI) is used to estimate SCNSL risk, its limited sensitivity highlights the need for more reliable biomarkers to improve risk stratification and enable earlier intervention. Methods We evaluated pretreatment levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) in both peripheral blood (PB) and cerebrospinal fluid (CSF), and compared clinical characteristics between DLBCL patients with and without SCNSL. Results Fifty-six newly diagnosed DLBCL patients who received at least two treatment cycles were included. Compared to patients without CNS relapse, those with SCNSL exhibited distinct clinical features: more frequent B symptoms, increased bone marrow involvement, and lower B-cell lymphoma 6 (BCL6) immunohistochemical positivity. Biochemically, SCNSL patients showed elevated serum IL-10 levels, higher serum IL-10/IL-6 ratios, increased CSF IL-10 concentrations, and markedly elevated CSF IL-10/IL-6 ratios. On multivariate analysis, a serum IL-10/IL-6 ratio >= 2.30 independently predicted both progression-free survival (PFS) (HR = 7.300, p = 0.010) and SCNSL development (OR = 43.200, p = 0.001). Notably, time to CNS relapse did not significantly differ between high- and non-high-risk groups defined by CNS-IPI (chi(2) = 1.654, p = 0.198). However, incorporating the serum IL-10/IL-6 ratio into the CNS-IPI yielded a refined scoring model-CNS-IPI-ratio-where the high-risk group had a significantly shorter median time to CNS relapse compared to the non-high-risk group (22.32 vs. 40.35 months;chi(2) = 5.680, p = 0.017). Although survival outcomes were similar between high- and non-high-risk groups based on the NCCN-IPI alone (p > 0.05), adding the serum IL-10/IL-6 ratio identified signif

关键词： Asthma   Anti-IL-5   Anti-IL5R   ACQ5  

摘要： In recent years, the use of monoclonal antibodies directed against interleukin-5 (anti-IL-5) and its receptor alpha (anti-IL-5R) has proven to be an effective therapeutic option for patients with severe asthma by reducing the number of eosinophils, which may promote disease remission. This study aimed to evaluate clinical improvement and remission in patients with severe asthma treated with anti-IL-5 and anti-IL-5R antibodies over a period of 12 months. A cohort study was conducted with 49 patients diagnosed with severe eosinophilic asthma and who did not respond to conventional treatment. During follow-up, medical control was performed every 3 months using spirometry, eosinophil counts, quality of life scales, and disease control. The results revealed an improvement in FEV1 after 3 months of treatment, with statistical significance at 12 months in patients treated with anti-IL-5 and at 9 months in those treated with anti-IL-5R. In addition, better perceptions of asthma control and quality of life were observed, with significant differences at 6 and 12 months. Correlations between spirometry and ACT, ACQ, and AQLQ reflect a progressive recovery of well-being and function. Finally, the remission rate was 41.1% with anti-IL-5 treatment and 47.3% with anti-IL-5R treatment after one year of follow-up. These findings support the efficacy of anti-IL-5 and anti-IL-5R treatment in improving severe asthma control and patients' quality of life, suggesting their key role in disease remission.

关键词： cerebral malaria   GTPases   olfactory bulb   Gbp4   Irgb6  

摘要： Cerebral malaria (CM) is a severe and often fatal complication of Plasmodium falciparum infection. Although much progress has been made in understanding CM, the precise pathogenesis remains elusive. The olfactory bulb (OB) has emerged as a critical site of immunopathology in experimental cerebral malaria (ECM) models, but its contribution to disease progression is not fully understood. To investigate the molecular mechanisms driving early ECM pathogenesis, we conducted transcriptomic profiling of the OB to identify key genes associated with disease onset. Our analysis revealed significant early upregulation of interferon (IFN)-inducible GTPases, particularly Irgb6 and Gbp4, effectors downstream of IFN-gamma but not IFN-alpha/beta signaling, suggesting their involvement in ECM pathology. Using Gbp4-/-, Irgb6-/-, and double knockout (Irgb6-/- Gbp4-/-) mice, we identified a pathological role for these GTPases. Mechanistically, we found that double-knockout mice exhibited increased infiltration of CD4+ and CD8+ T cells into the brain but with reduced T cell functionality and impaired antigen presentation by endothelial cells, leading to enhanced parasite accumulation in the OB. This disruption in immune regulation ultimately conferred improved survival in the Irgb6-/- Gbp4-/- mice and indicated the pathological impact of Gbp4 and Irgb6 in ECM. These findings reveal that Gbp4 and Irgb6 play important roles in the early immunopathogenesis of ECM by modulating antigen processing and presentation in the OB, thereby shaping immune cell dynamics. Our work shows the dual role of Irgb6 and Gbp4 GTPases in host defence and immunopathology and offers new insights into ECM mechanisms and antigen *** malaria (CM) arises from an excessive inflammatory response and blood-brain-barrier (BBB) dysfunction in Plasmodium-infected hosts, but the precise mechanisms driving early-stage pathogenesis remain unclear. Through RNA sequencing of the olfactory bulb (OB)

关键词： span>VitiligoAryl Hydrocarbon ReceptorIFN-γ signallingImmune checkpointsKynurenine pathway  

关键词： Synthesis   pyridazine   pyridazinone   anti-inflammatory   prostaglandin   cytokine   TxA2   TNF-alpha   and IL-6  

摘要： Inflammation is a fundamental biological reaction to harmful stimuli, which is crucial in the initiation and advancement of different diseases, including rheumatoid arthritis, cardiovascular conditions, neurological disorders such as Alzheimer's and Parkinson's, and multiple cancer types. Chronic inflammation, in particular, contributes to irreversible tissue damage and the progression of disease. Thus, the suppression of key inflammatory mediators has become a promising therapeutic approach. Thromboxane A2 (TxA2), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) are among the mediators that have been thoroughly investigated for their roles in regulating immune responses and sustaining inflammation;therefore, targeting these mediators offers substantial therapeutic potential. In recent years, significant attention has been focused on heterocyclic compounds, especially pyridazine and pyridazinone derivatives, owing to their structural diversity and extensive biological activity. These scaffolds have shown significant effectiveness in regulating inflammatory pathways by limiting TxA2 production, reducing TNF-alpha release, and disrupting IL-6 signaling. This review presents a comprehensive overview of pyridazine and pyridazinone-based compounds as potential anti-inflammatory agents. It highlights both traditional and current synthetic strategies used in their development and explores their mechanisms of action with respect to key inflammatory targets. Additionally, the study examines recent pharmacological assessments and preclinical results, offering insights into the medicinal uses of these substances. A brief perspective on future research directions is also included, emphasizing the need for further structural optimization, in vivo validation, and clinical translation. Collectively, these results highlight the potential of pyridazine and pyridazinone derivatives in the development of advanced anti-inflammatory pharmaceuticals.