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T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus
- Source :
- PLoS ONE, PLoS ONE, Vol 10, Iss 11, p e0141171 (2015)
- Publication Year :
- 2015
- Publisher :
- Public Library of Science, 2015.
-
Abstract
- BackgroundT 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.MethodsGene 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.ResultsWe 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.ConclusionsUnbiased 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.
- Subjects :
- Adult
Male
Science
T cell
T-Lymphocytes
Bioinformatics
medicine.disease_cause
Autoimmunity
Transcriptome
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Lupus Erythematosus, Systemic
Gene
030304 developmental biology
0303 health sciences
Multidisciplinary
Lupus erythematosus
biology
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
medicine.disease
Acquired immune system
3. Good health
Protein Structure, Tertiary
Gene expression profiling
medicine.anatomical_structure
Case-Control Studies
Immunology
biology.protein
Medicine
Female
Antibody
Biomarkers
030215 immunology
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....94d88b76903e8e41dc6a044e8abd64f6