T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus

作者：Sean J. Bradley, Abel Suárez‐Fueyo, David R. Moss, Vasileios C. Kyttaris, George C. Tsokos · 发表于：PLoS ONE · 年份：2015 · DOI：10.1371/journal.pone.0141171 · 被引用次数：53 · 研究领域：Systemic Lupus Erythematosus Research、Single-cell and spatial transcriptomics、T-cell and B-cell Immunology

BACKGROUND: T cells regulate the adaptive immune response and have altered function in autoimmunity. Systemic Lupus Erythematosus (SLE) has great diversity of presentation and treatment response. Peripheral blood component gene expression affords an efficient platform to investigate SLE immune dysfunction and help guide diagnostic biomarker development for patient stratification. METHODS: Gene expression in peripheral blood T cell samples for 14 SLE patients and 4 controls was analyzed by high depth sequencing. Unbiased clustering of genes and samples revealed novel patterns related to disease etiology. Functional annotation of these genes highlights pathways and protein domains involved in SLE manifestation. RESULTS: We found transcripts for hundreds of genes consistently altered in SLE T cell samples, for which DAVID analysis highlights induction of pathways related to mitochondria, nucleotide metabolism and DNA replication. Fewer genes had reduced mRNA expression, and these were linked to signaling, splicing and transcriptional activity. Gene signatures associated with the presence of dsDNA antibodies, low complement levels and nephritis were detected. T cell gene expression also indicates the presence of several patient subtypes, such as having only a minimal expression phenotype, male type, or severe with or without induction of genes related to membrane protein production. CONCLUSIONS: Unbiased transcriptome analysis of a peripheral blood component provides insight on a...