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Title
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Modulation of the complement system in monocytes contributes to tuberculosis-associated immune reconstitution inflammatory syndrome
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Author
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Institution/Organisation
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TB-IRIS Study Group
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Abstract
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| Objective:Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a common complication in HIV-TB co-infected patients receiving combined antiretroviral therapy (cART). This study investigated a putative contribution of monocytes to the development of TB-IRIS.Design:A prospective study was designed to compare gene expression between patients who developed TB-IRIS with matched non-TB-IRIS controls.Methods:We performed a hypothesis-generating transcriptome analysis on monocytes of HIV-TB co-infected patients. Identified pathways were subsequently analysed in patients' monocytes before and shortly after cART initiation, in a technically independent set-up (nCounter). Additionally, protein expression and enzymatic activities of specific factors were assessed at the systemic level.Results:Pathway analysis of microarray datasets and focused gene expression study revealed that, even before initiation of cART, the complement system is dysregulated in HIV-TB co-infected patients who are predisposed to developing TB-IRIS. Detailed analysis revealed differences between TB-IRIS patients and matched non-TB-IRIS cases, at the level of the balance between the effector C1Q and the inhibitor C1-INH, both before and 2 weeks after cART initiation. These differences were mirrored by increases in the downstream pro-inflammatory complement factor C5 over the course of 2 weeks of cART. Our results suggest that inappropriate control of complement activation could be associated with the flaring up' of inflammation observed during TB-IRIS.Conclusion:The current study reveals a contribution of monocytes and the complement system to TB-IRIS development. An intriguing possibility is that the development of TB-IRIS may depend partially on the relative balance between C1Q and C1-INH. |
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Language
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English
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Source (journal)
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AIDS. - London
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Publication
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London
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2013
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ISSN
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0269-9370
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DOI
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10.1097/QAD.0B013E328361648B
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Volume/pages
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27
:11
(2013)
, p. 1725-1734
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ISI
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000326841200005
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Full text (Publisher's DOI)
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