Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency

Joon Park, Indira Munagala, Hui Xu, Derek Blankenship, Patrick Maffucci, Damien J. Chaussabel, Jacques Banchereau, Virginia Pascual, Charlotte Cunningham-Rundles

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

About half of all subjects with common variable immune deficiency (CVID) are afflicted with inflammatory complications including hematologic autoimmunity, granulomatous infiltrations, interstitial lung disease, lymphoid hyperplasia and/or gastrointestinal inflammatory disease. The pathogenesis of these conditions is poorly understood but singly and in aggregate, these lead to significantly increased (11 fold) morbidity and mortality, not experienced by CVID subjects without these complications. To explore the dysregulated networks in these subjects, we applied whole blood transcriptional profiling to 91 CVID subjects, 47 with inflammatory conditions and 44 without, in comparison to subjects with XLA and healthy controls. As compared to other CVID subjects, males with XLA or healthy controls, the signature of CVID subjects with inflammatory complications was distinguished by a marked up-regulation of IFN responsive genes. Chronic up-regulation of IFN pathways is known to occur in autoimmune disease due to activation of TLRs and other still unclarified cytoplasmic sensors. As subjects with inflammatory complications were also more likely to be lymphopenic, have reduced B cell numbers, and a greater reduction of B, T and plasma cell networks, we suggest that more impaired adaptive immunity in these subjects may lead to chronic activation of innate IFN pathways in response to environmental antigens. The unbiased use of whole blood transcriptome analysis may provides a tool for distinguishing CVID subjects who are at risk for increased morbidity and earlier mortality. As more effective therapeutic options are developed, whole blood transcriptome analyses could also provide an efficient means of monitoring the effects of treatment of the inflammatory phenotype.

Original languageEnglish
Article numbere74893
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - 16 Sep 2013
Externally publishedYes

Fingerprint

Common Variable Immunodeficiency
immunosuppression
interferons
Interferons
Blood
blood
Chemical activation
Pulmonary diseases
Gene Expression Profiling
Infiltration
B-lymphocytes
morbidity
B-Lymphocytes
Up-Regulation
Genes
Cells
Morbidity
Plasmas
Antigens
autoimmunity

ASJC Scopus subject areas

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

Cite this

Park, J., Munagala, I., Xu, H., Blankenship, D., Maffucci, P., Chaussabel, D. J., ... Cunningham-Rundles, C. (2013). Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency. PLoS One, 8(9), [e74893]. https://doi.org/10.1371/journal.pone.0074893

Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency. / Park, Joon; Munagala, Indira; Xu, Hui; Blankenship, Derek; Maffucci, Patrick; Chaussabel, Damien J.; Banchereau, Jacques; Pascual, Virginia; Cunningham-Rundles, Charlotte.

In: PLoS One, Vol. 8, No. 9, e74893, 16.09.2013.

Research output: Contribution to journalArticle

Park, J, Munagala, I, Xu, H, Blankenship, D, Maffucci, P, Chaussabel, DJ, Banchereau, J, Pascual, V & Cunningham-Rundles, C 2013, 'Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency', PLoS One, vol. 8, no. 9, e74893. https://doi.org/10.1371/journal.pone.0074893
Park, Joon ; Munagala, Indira ; Xu, Hui ; Blankenship, Derek ; Maffucci, Patrick ; Chaussabel, Damien J. ; Banchereau, Jacques ; Pascual, Virginia ; Cunningham-Rundles, Charlotte. / Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency. In: PLoS One. 2013 ; Vol. 8, No. 9.
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