Longitudinal analysis of sarcoidosis blood transcriptomic signatures and disease outcomes

Previously, we demonstrated concordance in differentially expressed genes in sarcoidosisblood and lung, implicating shared dysfunction of specific immunepathways. In the present study, we hypothesised that expression levels of candidate genesin sarcoidosisblood could predict and track with disease outcomes longitudinally. We applied Ingenuity Pathway Analysisto a cross-sectional derivation microarray dataset (n=38) to identify canonical pathways and candidate genesassociated with sarcoidosis. In a separate longitudinal sarcoidosiscohort (n=103), we serially measured 48 candidate genetranscripts, and assessed their relation to disease chronicity and severity. In the cross-sectional derivation study, pathway analysisshowed upregulation of genes related to interferon signalling and the role of pattern recognition receptors, and downregulation of T-cell receptor (TCR) signalling pathways in sarcoidosis. In the longitudinal cohort, factor analysis confirmed coregulation of genes marking these pathways and identified CXCL9as an additional candidate pathway. CXCL9and TCR factors discriminated between chronic versus nonprogressive disease, and CXCL9predicted disease outcomes longitudinally. Interferon factor was similarly increased in both disease phenotypes. Factors associated with lung function decline included decreased TCR factor and increased CXCL9. These findings demonstrate blood transcriptomic signatures reflecting TCR signalling and CXCL9predict sarcoidosischronicity and correlate with disease severity longitudinally. Blood gene transcript measurements predict sarcoidosischronicity and severity longitudinally