GSE134979 Activation of Interferon and Complement Pathways in Thrombotic Microangiopathy  

Contributors : Sonata Jodele ; Nathan Luebbering ; Mario Medvedovic ; Christopher E Dandoy ; Nicholas J Gloude ; Michael B Jordan ; Daniella L Erez ; Benjamin L Laskin ; Jenny Chen ; Stella M DaviesSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTransplant-associated thrombotic microangiopathy (TA-TMA) is a significant cause of mortality after hematopoietic stem cell transplant (HSCT). Complement blockade is an effective therapeutic strategy for TA-TMA, but some patients with severe disease lack a complete response, prompting a search for additional targetable endothelial injury pathways. We performed transcriptome analysis of peripheral blood mononuclear cells collected prior to HSCT and at onset of TA-TMA and observed significant up-regulation of classical and alternative complement pathways during active TA-TMA. At resolution of TA-TMA after eculizumab therapy, essentially all up-regulated genes and pathways returned to baseline expression levels, supporting the clinical practice of successfully discontinuing complement blockade after resolution of TA-TMA. Further analysis of the global transcriptional regulatory network showed a notable interferon signature associated with TA-TMA with increased STAT1 and STAT2 signaling. To confirm our observations, we documented a high incidence of clinically significant TMA in children with hemophagocytic lymphohistiocytosis (HLH), an interferon gamma-driven disease, outside the setting of tran...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research