Immune Profiling in CD59 Deficiency: From Single-Patient scRNA-seq to Therapeutic Insights
CD59 deficiency is a rare disorder in which cells are vulnerable to uncontrolled complement-mediated immune attacks. To investigate its mechanisms of action, we applied single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs). Because only one CD59-deficient patient sample was available, we developed a pairwise differential expression pipeline that leverages multiple matched controls and significantly reduces false-positive discoveries. Using this approach, we uncovered a distinct exhausted immune profile marked by downregulation of NF-κB signaling and evidence of oxidative stress, findings that illuminate the pathophysiology of CD59 deficiency and also suggest potential avenues for therapeutic intervention
