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Project description:Sickle Cell Disease mouse lung
| PRJNA472342 | ENA
Project description:Sickle cell disease (SCD) is a red blood cell disorder associated with hemolysis and inflammation affecting hematopoietic system homeostasis. While both innate and T cell driven adaptive immune responses are involved in driving SCD-linked inflammation, the involvement of the B cell compartment in the pathophysiology of SCD, especially in pediatric patients, is much less understood. To determine the range of immune changes, we assessed the frequency of twelve immune populations via flow cytometry and levels of B cell related cytokines of the peripheral blood (PB) of pediatric (n=13) and adult (n=12) patients with SCD on hydroxyurea as compared to pediatric (n=5) and adult (n=10) race-matched controls. We also evaluated bulk RNA sequencing of the PB of pediatric SCD patients and controls. The majority of SCD patients carried the hemoglobin SS genotype (92.3% pediatrics and 66.7% adults). Mean Hydroxyurea dose was 23.4 mg/kg and 20.0 mg/kg for pediatric SCD (PSCD) and adult SCD (ASCD), respectively. Laboratory data revealed anemia with mean hemoglobin 9.4 g/dl in PSCD and 9.7 g/dl in ASCD with elevated hemolysis in pediatric and adult SCD with mean reticulocyte count of 7.1% in PSCD and 8.8% in ASCD with mean absolute reticulocyte count (ARC) 203 ± 94 for pediatric SCD and 214 ± 169 for adult SCD. Flow cytometry data revealed 1.9-fold increase (p value 0.012) of CD3+CD4+ cells in pediatric SCD versus pediatric controls; this change was not seen in adult SCD versus adult controls (decrease 17%, p value 0.302). Pediatric SCD patients had 3.5-fold increase (p=0.005) in CD19+ B cells without further increase in differentiated B cells, and this change was not seen in adult SCD versus adult controls (increase 7%, p value 0.815). We performed bulk RNA sequencing on the PB of pediatric patients with SCD as compared to the pediatric controls. Obtained transcriptomic data indicated significant changes in transcripts linked to humoral immunity. Over Representation Analysis (ORA) of cell type revealed upregulation of transcripts linked to pro-B cells (27 genes, top 3:E2F2,RAD51,ASPM) and plasma cells (37 genes, top 3:IGF1,TNFRSF17,DERL3). Analysis of B cell related cytokines revealed significant increase in IL2 (p value 0.013), IL4 (p value 0.026), TNFβ (p value 0.039), and IL13 (p value 0.034) inpediatric SCD versus pediatric controls withno significance for these cytokines in adult SCD versus adult controls. BAFF was elevated in both pediatric and adult SCD versus age-matched controls (p value0.041 and p value 0.005, respectively). In sum, our data indicate significant changes in CD4+ and CD19+ cells andsuggest significant alteration of the B cell maturation in pediatric SCD samples. Our findings point to previously unreported effect of SCD on the humoral immune system in children with SCD treated with hydroxyurea, warranting further investigation.
2025-05-15 | GSE262659 | GEO
Project description:Understanding how genetic disorders affect CD8+ T cells in the tumor microenvironment is key to improving cancer immunotherapy. Individuals with sickle cell disease (SCD), the most prevalent inherited blood disorder, have a higher risk of developing certain cancers than the general population, but the mechanisms driving this increased risk remain unclear. Our study revealed that SCD altered CD8+ T cell 3D genome architecture, triggering ferroptosis and weakening anti-tumor immunity, thereby promoting tumor growth. Using murine and humanized SCD models, we found that disrupted chromosomal interactions in CD8+ T cells reduced the expression of anti-ferroptotic genes, including SLC7A11 and hydrogen sulfide (H2S) biogenesis genes, thereby increasing susceptibility to ferroptosis. Therapeutic restoration of H2S concentration in SCD mice rescued SLC7A11 expression, mitigated ferroptosis, and enhanced immune and anti-tumor responses. These findings highlight the impact of inherited disorders on cancer immunity and suggest precision immunotherapy strategies for affected individuals.
2025-05-12 | GSE247240 | GEO
Project description:Sickle cell disease (SCD) is a devastating hemoglobinopathy prevalent in Chhattisgarh and other states of central India. Clinical features in SCD arise mainly due to anemia and vaso-occlusion and inflammation leading to gradual multiple organ failure. Vaso-occlusive crisis (VOC) is a common cause of sudden death among SCD patients. Aim of the study was to evaluate gene expression in patients of SCD in a quest to search up-regulated genes in VOC.
2017-06-30 | GSE72999 | GEO
Project description:Circulating platelets from Sickle cell disease (SCD) patients express distinct gene expression patterns that regulate function. The objective of this study is to identify a role of post-transcriptional regulation of the platelet transcriptional signaling by microRNAs. Comparison of microRNA expression in platelets from SCD patients and control subjects, from 2 cohorts-University of Pittsburgh and National Institutes of Health.
2013-06-20 | E-GEOD-41574 | biostudies-arrayexpress
Project description:Sickle cell disease (SCD) is caused by a pathogenic hemoglobin (Hb) mutation, yet patients can have dramatically variable clinical manifestations. Here we address the genetic basis of this clinical heterogeneity. Using a systems genetics approach, we performed whole blood gene expression analysis and eQTL analysis on different clinical phenotypes in SCD patients. We generated whole blood gene expression profiles for 311 West-African children recruited from the National Sickle Cell Disease Centre in Cotonou, Benin which included 250 patients with varying degrees of SCD severities and 61 age-matched controls. SCD is caused by a point-mutation in the beta-hemoglobin gene that changes the normal HbAA protein into, most often, an abnormal HbSS or HbSC protein. The SCD patients recruited in the study either had HbSS or HbSC phenotypes and were categorized into different 3 clinical states based on follow-up status (Rahimy, MC, et al. Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in sub-Saharan African setting. Bood 102, 834-838. 2002). When patients are refered to the clinic, they are enrolled when they are in steady-state condition, and are labeled as entry (E). Patients followed at the SCD clinic are labeled as FU. Control patients were recruited and are labeled as C. Patients were also assigned a severity score (Sebastiani, P. et al. A network model to predict the risk of death in sickle cell disease. Blood 110, 2727-2735, 2007). Hemoglobin protein status (Hb phenotype) was confirmed for each patient using standard electrophoretic techniques. We generated genotypes for 263 of these individuals and performed principal component analysis (PCA) which identified 2 signigicant genotypic principal components (gPC1 and gPC2). Using the gene expression and genotyping data, we performed an eSNP analysis. . Gene expression data presented in this study.
2014-07-01 | E-GEOD-35007 | biostudies-arrayexpress
Project description:To date, little is known about lung disease pathogenesis in patients with sickle cell disease (SCD). Acute chest syndrome (ACS) is a significant cause of morbidity and premature.mortality in SCD, but preventative, diagnostic, and therapeutic options are limited. Further, ACS and acute vasoccclusive pain crises (VOC) can have overlapping features such as chest pain, which causes a diagnostic dilemma for clinicians. We aimed to explore changes in gene expression profiles in patients with SCD at baseline and during hospitalization for VOC or ACS in order to better understand ACS disease pathogenesis.
2019-11-05 | GSE139912 | GEO
Project description:We sequenced mRNA from the dorsal root ganglion (DRG) of transgenic mouse models of sickle cell disease (SCD) and their transgenic controls. Each genotype (strains) were divided into two age groups and each age groups were subjected to two treatment conditions (each simulating acute and chronic pain respectively). Each of these 8 groups had 6 male mice (except one group had 7 mice) resulting into a total of 49 samples. The goal of mRNA sequencing of these samples is to identify genetic signatures associated with transition from acute to chronic pain in SCD.
2017-04-05 | GSE86418 | GEO
Project description:β-hemoglobin disorders, such as sickle cell disease (SCD) and β-thalassemia (BT), are the most common inherited monogenic blood disorders globally. Despite decades of research, there are only four FDA-approved medications available for the management of SCD with hydroxyurea (HU) being the most widely used drug that partially benefits patients by inducing fetal hemoglobin (HbF) production. On the other hand, there are no approved oral drugs currently available for β-thalassemia patients. To our knowledge, there are currently no well-characterized erythroid progenitor cell lines available that can accurately replicate the pathophysiology of SCD and BT while also having the same genetic background apart from the disease mutation enabling consistency and reproducibility. Our novel, physiologically relevant cellular systems provide a plethora of avenues for researchers to investigate various applications related to parasite invasion, drug validation, and genome-editing in the context of SCD and BT.
2024-02-07 | PXD044642 | Pride
Project description:SCD had hemolysis with elevated levels of heme and iron, which induced ferroptosis. Here, we found Nrf2 knockout in SCD mice accumulated the levels of the metabolite L-2-hydroxyglutarate (L2HG), which impaired ferroptosis stress response to exacerbate SCD symptom. Mechanistically, L2HG was found to regulate the expression of genes involved in the iron and heme metabolism via histone epigenetic hypermethylation. Our findings indicate an important role of Nrf2/L2HG in SCD for ferroptosis response.
2021-11-19 | GSE188695 | GEO