De Smit, E and Lukowski, SW and Anderson, L and Senabouth, A and Dauyey, K and Song, S and Wyse, B and Wheeler, L and Chen, CY and Cao, K and Wong Ten Yuen, A and Shuey, N and Clarke, L and Lopez Sanchez, I and Hung, SSC and Pebay, A and Mackey, DA and Brown, MA and Hewitt, AW and Powell, JE, Longitudinal expression profiling of CD4+ and CD8+ cells in patients with active to quiescent giant cell arteritis, BMC Medical Genomics, 11, (1) Article 61. ISSN 1755-8794 (2018) [Refereed Article]
Copyright 2018 The Authors Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Methods: We recruited 16 patients with histological evidence of GCA at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and aimed to collect blood samples at six time points: acute phase, 2-3 weeks, 6-8 weeks, 3 months, 6 months and 12 months after clinical diagnosis. CD4+ and CD8+ T-cells were positively selected at each time point through magnetic-assisted cell sorting. RNA was extracted from all 195 collected samples for subsequent RNA sequencing. The expression profiles of patients were compared to those of 16 age-matched controls.
Results: Over the 12-month study period, polynomial modelling analyses identified 179 and 4 statistically significant transcripts with altered expression profiles (FDR < 0.05) between cases and controls in CD4+ and CD8+ populations, respectively. In CD8+ cells, two transcripts remained differentially expressed after 12 months; SGTB, associated with neuronal apoptosis, and FCGR3A, associatied with Takayasu arteritis. We detected genes that correlate with both symptoms and biochemical markers used for predicting long-term prognosis. 15 genes were shared across 3 phenotypes in CD4 and 16 across CD8 cells. In CD8, IL32 was common to 5 phenotypes including Polymyalgia Rheumatica, bilateral blindness and death within 12 months.
Conclusions: This is the first longitudinal gene expression study undertaken to identify robust transcriptomic biomarkers of GCA. Our results show cell type-specific transcript expression profiles, novel gene-phenotype associations, and uncover important biological pathways for this disease. In the acute phase, the gene-phenotype relationships we have identified could provide insight to potential disease severity and as such guide in initiating appropriate patient management.
|Item Type:||Refereed Article|
|Keywords:||CD4 & CD8 T lymphocytes, disease biomarkers, expression profiling, giant cell arteritis, magnetic-assisted cell sorting, RNA sequencing, transcriptome|
|Research Division:||Medical and Health Sciences|
|Research Group:||Ophthalmology and Optometry|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Hearing, Vision, Speech and Their Disorders|
|Author:||Hewitt, AW (Professor Alex Hewitt)|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||1 View Download Statistics|
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