The role of monocytes in the development of tuberculosis-associated immune reconstitution inflammatory syndrome

H.T. Tran, R. Van den Bergh, T.N. Vu, K. Laukens, W. Worodria, Marguerite Massinga Loembé, Robert Colebunders, Luc Kestens, P. De Baetselier, G. Raes

Research output: Contribution to journalA1: Web of Science-article

Abstract

BACKGROUND: Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication of combined antiretroviral therapy (cART) in HIV-TB co-infected patients. However, the disease mechanism is poorly understood, prognosis of TB-IRIS is currently impossible, and diagnosis is highly challenging. We analyzed whether the gene expression of monocytes could be correlated with TB-IRIS pathogenesis and could be used to classify patients predisposed to TB-IRIS. METHODS: Monocyte gene expression was compared between patients who developed TB-IRIS and matched controls. We carried out whole-genome expression profiling using Affymetrix GeneChip(R) ST 1.1 arrays at two time-points: before cART initiation (baseline) and at week two post-cART initiation. For each time-point, we used different statistical approaches to identify molecular signatures which could be used as classifiers. We also functionally mapped the modulated cellular pathways using the software package Ingenuity Pathway Analysis. RESULTS: At baseline, before introduction of cART and before onset of symptoms, monocyte gene expression was already perturbed in patients who subsequently developed TB-IRIS, indicating a possible involvement of monocytes in TB-IRIS predisposition. The differences in monocyte gene expression in TB-IRIS patients became even more clear after two weeks of cART (when TB-IRIS commonly occurs), with more than 100 genes for which expression showed a fold change greater than 1.5. Both at baseline and at week two post-cART initiation, a classifier of 8 and 9 genes, respectively could be built, which allowed discrimination of TB-IRIS cases and controls. Pathway analyses revealed that the majority of the dysregulated genes in TB-I.
Original languageEnglish
JournalImmunobiology
Volume219
Issue number1
Pages (from-to)37-44
Number of pages8
ISSN0171-2985
DOIs
Publication statusPublished - 2014

Keywords

  • Viral diseases
  • HIV
  • AIDS
  • Co-infections
  • Bacterial diseases
  • Tuberculosis
  • Mycobacterium tuberculosis
  • Immune reconstitution inflammatory syndrome (IRIS)
  • IRIS
  • HAART
  • Antiretrovirals
  • Correlation
  • Gene expression
  • Monocytes
  • Pathogenesis
  • Genetic predisposition to disease
  • Classification
  • Uganda
  • Africa-East

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