title: T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus.
abstract: 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 autoimmune pathophysiology and patient variability. We present an open source workflow and richly annotated dataset to support investigation of T cell biology, develop biomarkers for patient stratification and perhaps help indicate a source of SLE immune dysfunction.
authors.affiliation: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Bradley
authors.affiliation: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Abel
authors.initials: A
authors.lastname: Suarez-Fueyo
authors.affiliation: Department of Anesthesiology, Tufts Medical Center, Boston, Massachusetts, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Moss
authors.affiliation: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Vasileios C
authors.initials: VC
authors.lastname: Kyttaris
authors.affiliation: Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D008297:Male; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome / Q000235:genetics*
chemical_list: D015415:Biomarkers