Project description:Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) frequently complicates combined anti-retroviral therapy (ART) and anti-tubercular therapy in HIV-1 co-infected tuberculosis (TB) patients. The immunopathological mechanism underlying TB-IRIS is incompletely defined. Differential transcript abundance in PBMC from IRIS and control patients stimulated with heat killed H37Rv was determined by microarray Blood samples were collected during longitudinal observational studies of TB-IRIS patients and controls (both groups HIV-infected patients placed on antiretroviral treatment). PBMC were stimulated with heat killed H37Rv and RNA extracted.
Project description:Patients with HIV-associated TB are known to experience systemic hyperinflammation, clinically known as immune reconstitution inflammatory syndrome (IRIS), following the commencement of antiretroviral therapy (ART). No prognostic markers or biomarkers have been identified to date and little is known about the mechanism mediating the hyperinflammation. We recruited a prospective cohort of 63 patients with HIV-associated TB, 33 of whom developed TB-IRIS. Of which transcriptomic profiling was performed using longitudinal whole blood RNA samples from 15 non-IRIS and 17 TB-IRIS patients. Transcriptomic signatures that distinguish patients who would eventually develop IRIS were identified as early as week 0.5 (2-5 days post-ART) and predicted a downstream activation of proinflammatory cytokines. At the peak of IRIS (week 2), transcriptomic signatures were overrepresented by innate receptor signaling pathways including toll-like receptor, IL-1 receptor and TREM-1.
Project description:Previous Genome-wide association studies (GWASs) have identified susceptibility loci of primary angle closure glaucoma (PACG), but applicating these findings is difficult. Although shallow anterior chamber depth (ACD) and short axial length (AL) are characteristic phenotypes of PACG, current GWAS variants do not show any correlation with these features, calling for the identification of more risk factors . Here, thicker and enlarged iris was identified as a significant independent risk factors. By employing allelic-specific STARR-seq and assay for transposase-accessible chromatin using sequencing (ATAC-seq), we screened disease-related variants in linkage disequilibrium and identified 2 causative variants in iris. Alterations in these variants may contribute to the pathogenic iris phenotype by upregulating the expression of PLEKHA7 and C10orf53, potentially regulating PACG development and progression. Our efforts nominate the important role of iris and identify pathogenic SNP-target gene interactions for PACG, providing a potentially powerful approach for interpreting noncoding variation of diseases.
Project description:Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) frequently complicates combined anti-retroviral therapy (ART) and anti-tubercular therapy in HIV-1 co-infected tuberculosis (TB) patients. The immunopathological mechanism underlying TB-IRIS is incompletely defined. Differential transcript abundance in PBMC from IRIS and control patients stimulated with heat killed H37Rv was determined by microarray