Sex-based comparison of CD4+ T cell DNA methylation patterns in SLE reveals pro-inflammatory epigenetic changes in men
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PROVIDER: PRJNA857452 | ENA |
REPOSITORIES: ENA
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Project description:Male patients with systemic lupus erythematosus (SLE) experience severe disease compared to female patients, despite the disease being more prevalent in females. For the time, we compared genome-wide differential methylation in CD4+ T cells between male (n=12) and female (n=10) SLE patients.
2023-06-07 | GSE207861 | GEO
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2007-11-24 | GSE9676 | GEO
Project description:Neisseria meningitidis (meningococcus) is usually transmitted via respiratory droplets, whereas its close relative, the gonococcus is sexually transmitted. Invasive meningococcal disease due to isolates of serogroup C increased in Europe and the United States among men who have sex with men (MSM). These isolates were also recovered from cases of urethritis suggesting sexual transmission. Genome sequencing of representative strains revealed that isolates from MSM and urethritis cases belonged to a unique clade within clonal complex11. Proteome analysis showed expression of nitrite reductase by these isolates, enabling anaerobic growth as in gonococci. Invasive isolates from MSM, but not urethritis isolates expressed functional human factor H (hfH) binding protein associated with enhanced survival in transgenic mice expressing hfH, a complement regulatory protein. Our data provide a unique example of meningococcal evolution with adaptation to sexual transmissibility, initially associated with low virulence but with subsequent fHbp-associated invasiveness. Implications for vaccination strategies are discussed.
2016-05-18 | PXD001498 | Pride
Project description:Aortic stenosis (AS) is a degenerative valve disease characterized by active remodelling of valve leaflets. The main hallmarks of stenotic aortic valves (AVs) include fibrosis, inflammation, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is a pro-inflammatory and pro-osteogenic lectin with a prominent role in the progression of AS. In this work, we aim to analyze potential sex-differences in the impact of Gal-3 in AS. 226 patients (61.50% men) with severe AS undergoing surgical valve replacement were recruited. In AVs, Gal-3 expression and its relationship with inflammatory, osteogenic and angiogenic markers was assessed. Valve interstitial cells (VIC) derived from AV tissue were primary cultured to perform in vitro experiments. Proteomic analysis revealed that Gal-3 is over-expressed in VICs of male AS patients. Gal-3 secretion also showed to be higher in men’s VICs as compared to women. In human AV tissue, Gal-3 protein levels were significantly higher in men, with stronger immunostaining in VICs with myofibroblastic phenotype and valve endothelial cells. Gal-3 levels in AVs were positively correlated with inflammatory markers in both sexes. Gal-3 expression was also positively correlated with osteogenic markers mainly in men’s AV, and with angiogenic molecules only in this sex.
2024-05-31 | PXD042586 | JPOST Repository
Project description:Transcriptomic data from a clinical cohort of men who have sex with men (MSM) and controls.
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Project description:Background and study aims
Anal cancer is a growing problem in the UK. Almost 90% of these cancers are caused by the human papillomavirus (HPV). HPV infection in a weakened immune system can lead to abnormal cell changes which are graded as anal intraepithelial neoplasia (AIN) 1-3, with AIN 2 and AIN 3 considered to be high-grade neoplasia (AIN 2/3). These changes are called precancers, but it is not known how many, over what time period will turn to cancer. Although many doctors and scientists think we need to treat AIN 2/3 (precancer), as is done in women for cervical precancer to prevent cancer, there is no proven treatment for anal precancer (AIN 2/3) that will prevent anal cancer. Laser treatment may be an effective strategy to prevent anal cancer. The main aim of the study is to assess the long-term effect (up to 5 years) of laser treatment in preventing anal cancer in HIV-positive men who have sex with men with anal precancer.
Who can participate?
HIV-positive men who have sex with men, who have anal precancer
What does the study involve?
Participants are randomly allocated to one of two groups. Participants in the treatment group undergo laser ablation of their perianal (external) or anal canal (internal) disease under local anaesthetic injections. If the disease volume (extent) is large the ablation may be done under general anaesthetic as a day case. Rarely, it may be necessary to treat extensive disease as a staged procedure over more than one treatment visit. Participants in the active surveillance group receive no treatment. All participants are followed up every 6 months with standard examinations. The number of cancers, the effect of treatment on preventing new precancer, quality of life, and the costs of treatment are compared between the groups.
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Project description:Current non-specific immunosuppressive treatments for Systemic Lupus Erythematosus (SLE) show modest efficacy. In SLE the monocytic/macrophage (Mo/Mφ) system plays a key role in the initiation and perpetuation of the systemic autoimmune response. However, the distinct functions of the Mo/Mφ cellular subsets remain elusive. Herein, we demonstrate a distinct proteomic and transcriptomic profile of non-classical monocytes (NCM) of active patients with SLE with enhanced inflammatory features such as deregulated DNA repair, cell cycle and enhanced IFN signaling in parallel with cell differentiation and developmental cues. Ex-vivo assays revealed an upregulation of p53 due to enhanced DNA damage along with G0 cell cycle arrest of SLE NCM indicative of an inflammatory phenotype. This aberrant profile of NCM of active patients with SLE is linked with an activated macrophage-like and enriched M1 pro-inflammatory response. We envisage that enhanced autophagy in SLE NCM may drive their differentiation towards an M1-like macrophage profile contributing to disease severity. Together, these findings provide evidence of skewed differentiation of NCM towards an M1-like macrophage phenotype as a pathogenic feature of NCM in SLE.
2023-11-21 | PXD042539 | Pride
Project description:Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibodies, some of which are present in high titers in a sustained, B cell-independent fashion consistent with their generation from long-lived plasma cells (LLPC). Active SLE displays high numbers of circulating antibody-secreting cells (ASC). Understanding the mechanisms of generation and survival of SLE ASC would contribute important insight into disease pathogenesis and novel targeted therapies. We studied the properties of SLE ASC through a systematic analysis of their phenotypic, molecular, structural, and functional features. Our results indicate that in active SLE, relative to healthy post-immunization responses, blood ASC contain a much larger fraction of newly generated mature CD19-CD138+ASC similar to bone marrow (BM) LLPC. SLE ASC were characterized by morphological and structural features of premature maturation. Additionally, SLE ASC express high levels of CXCR4 and CD138, and molecular programs consistent with increased longevity based on pro-survival and attenuated pro-apoptotic pathways.Notably, SLE ASC demonstrate autocrine production of APRIL and IL-10 and experience prolonged in vitro survival. Combined, our findings indicate that SLE ASC are endowed with enhanced peripheral maturation, survival and BM homing potential suggesting that these features likely underlie BM expansion of autoreactive PC.
2023-08-08 | GSE235659 | GEO
Project description:Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African American (AA) men are disproportionately af-fected, on average suffering from a higher grade of the disease and at a younger age compared to men of European descent (EA). Fusion genes are chimeric products formed by the merging of two separate genes occurring as a result of chromosomal structural changes, for example, inversion or trans/cis-splicing of neighboring genes. They are known drivers of cancer and have been identified in 20% of cancers. Improvements in genomics technologies such as RNA-sequencing coupled with better algorithms for prediction of fusion genes has added to our knowledge of specific gene fu-sions in cancers. At present AA are underrepresented in genomic studies of prostate cancer. The primary goal of this study was to examine molecular differences in predicted fusion genes in a cohort of AA and EA men in the context of prostate cancer using computational approaches. RNA was purified from prostate tissue specimens obtained at surgery from subjects enrolled in the study. Fusion gene predictions were performed using four different fusion gene detection pro-grams. This identified novel putative gene fusions unique to AA and suggested that the fusion gene burden was higher in AA compared to EA men.
2022-04-16 | GSE152929 | GEO
Project description:Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibodies, some of which are present in high titers in a sustained, B cell-independent fashion consistent with their generation from long-lived plasma cells (LLPC). Active SLE displays high numbers of circulating antibody-secreting cells (ASC). Understanding the mechanisms of generation and survival of SLE ASC would contribute important insight into disease pathogenesis and novel targeted therapies. We studied the properties of SLE ASC through a systematic analysis of their phenotypic, molecular, structural, and functional features. Our results indicate that in active SLE, relative to healthy post-immunization responses, blood ASC contain a much larger fraction of newly generated mature CD19-CD138+ASC similar to bone marrow (BM) LLPC. SLE ASC were characterized by morphological and structural features of premature maturation. Additionally, SLE ASC express high levels of CXCR4 and CD138, and molecular programs consistent with increased longevity based on pro-survival and attenuated pro-apoptotic pathways.Notably, SLE ASC demonstrate autocrine production of APRIL and IL-10 and experience prolonged in vitro survival. Combined, our findings indicate that SLE ASC are endowed with enhanced peripheral maturation, survival and BM homing potential suggesting that these features likely underlie BM expansion of autoreactive PC.
2023-08-08 | GSE235658 | GEO