Dataset Information

Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia.

ABSTRACT:

Introduction

Classic ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by early onset ataxia, immune deficiency, sino-pulmonary disease, lymphoid/solid malignancies and telangiectasias. Prior studies have suggested that chronic inflammation and premature aging may contribute to the development of malignancy and pulmonary disease in people with A-T. To further examine the link between A-T and inflammation, we hypothesized that subjects with classic A-T would have greater enrichment of inflammatory pathways in peripheral blood mononuclear cells (PBMCs) compared to non A-T age-matched controls. To test this hypothesis we used RNAseq as an unsupervised approach to identify biological processes altered in people with classic A-T.

Methods

PBMCs were isolated from subjects with classic A-T and compared to non-A-T age-matched healthy controls. RNAseq with differential gene expression analyses was then performed. Selected genes were validated by RT-qPCR using cohorts of subjects consisting of classic A-T, mild A-T or non-A-T controls. Subjects with mild A-T were characterized by later onset/mild neurologic features and normal/near normal immune status.

Results

RNAseq revealed 310 differentially expressed genes (DEGs) including genes involved in inflammation, immune regulation, and cancer. Using gene set enrichment analysis, A-T subjects were found to have biological processes enriched for inflammatory and malignancy pathways. In examining a cohort of A-T subjects in which baseline serum IL8 and IL6 levels were measured previously, an association was found between higher serum IL8 levels and higher likelihood of developing malignancy and/or death in a subsequent 4-6 year period.

Conclusion

RNAseq using PBMCs from subjects with classic A-T uncovered differential expression of immune response genes and biological processes associated with inflammation, immune regulation, and cancer. Follow-up of A-T subjects over a 4-6 year period revealed an association between higher baseline serum IL8 levels and malignancy/death. These findings support a role for inflammation as a contributing factor in A-T phenotypes.

SUBMITTER: McGrath-Morrow SA

PROVIDER: S-EPMC6306200 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia.

McGrath-Morrow Sharon A SA Ndeh Roland R Collaco Joseph M JM Rothblum-Oviatt Cynthia C Wright Jennifer J O'Reilly Michael A MA Singer Benjamin D BD Lederman Howard M HM

PloS one 20181226 12

<h4>Introduction</h4>Classic ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by early onset ataxia, immune deficiency, sino-pulmonary disease, lymphoid/solid malignancies and telangiectasias. Prior studies have suggested that chronic inflammation and premature aging may contribute to the development of malignancy and pulmonary disease in people with A-T. To further examine the link between A-T and inflammation, we hypothesized that subjects with classic A-T would have ...[more]

PMID: 30586396

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Dataset Information

Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia.

Introduction

Methods

Results

Conclusion

Publications

Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia.

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