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

Sharon A. McGrath-Morrow*, Roland Ndeh, Joseph M. Collaco, Cynthia Rothblum-Oviatt, Jennifer Wright, Michael A. O’Reilly, Benjamin D. Singer, Howard M. Lederman

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations


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.

Original languageEnglish (US)
Article numbere0209496
JournalPloS one
Issue number12
StatePublished - Dec 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia'. Together they form a unique fingerprint.

  • Cite this

    McGrath-Morrow, S. A., Ndeh, R., Collaco, J. M., Rothblum-Oviatt, C., Wright, J., O’Reilly, M. A., Singer, B. D., & Lederman, H. M. (2018). Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia. PloS one, 13(12), [e0209496].