ABSTRACT
Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.
ABSTRACT
Coronavirus infectious disease 2019 (COVID-19) confirmed cases are characterized by T lymphopenia. Total apoptotic and cytotoxic T-lymphocyte antigen-4 (CTLA-4) expressing cells among CD4+/CD8+â cells were analyzed in 24 COVID-19 patients (16 out-patients and 8 in-patients) and 18 healthy volunteers using flow cytometry to detect their possible role in T lymphopenia. Hospitalized patients did not show significant difference compared to non-hospitalized patients. While the percentage and absolute count of CD4+/CD8+â cells were significantly reduced in COVID-19 cases compared to healthy control (Pâ <â .05), the proportion of apoptotic and CTLA-4 expressing CD4+/CD8+â cells were significantly up-regulated in COVID-19 patients (Pâ <â .05). In addition, apoptotic and CTLA-4+/CD4+â cells were directly related to dyspnea duration, chest CT score, ferritin, and C-reactive protein and inversely correlated with platelet count in COVID-19 patients. While apoptotic and CTLA-4+/CD8+â cells were directly related to lymphocyte count in COVID-19 patients. The apoptotic and CTLA-4+â cells were directly related to each other in CD4+/CD8+â cells (Pâ <â .05). White blood cells (WBCs) (×103/L), eosinophils (ratio and count), lymphocyte ratio, neutrophil ratio, neutrophil/lymphocyte ratio, neutrophil/CD4 ratio, neutrophil/CD8 ratio, CD4+â cells ratio, and CTLA-4+â cells percentage), and CD8+â cells (ratio, count, total apoptotic cell, and CD152â +â cells) were all found to be significantly altered in association with COVID-19. Total lymphopenia and depletion of CD4+/CD8+â cells are characterizing COVID-19 patients. Increased apoptosis and CTLA-4 expression in CD4+/CD8+â cells in COVID-19 and their correlations with reduced cell count and severity indicators as CRP and ferritin can be used for diagnosis and follow up of the clinical severity. Our current study proposes promising future diagnostic and therapeutic targets.