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Tran Thi Thanh Huyen Kuala Lumpur, Malaysia, 30 June-3 July 2013

Monocyte gene expression differentiates cases of TB-IRIS from controls both before and shortly after initiation of ART. Tran Thi Thanh Huyen Kuala Lumpur, Malaysia, 30 June-3 July 2013. BACKGROUND. TB-HIV coinfection challenges: TB-Immune Reconstitution Inflammatory Syndrome (TB-IRIS).

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Tran Thi Thanh Huyen Kuala Lumpur, Malaysia, 30 June-3 July 2013

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  1. Monocyte gene expression differentiates cases of TB-IRIS from controls both before and shortly after initiation of ART Tran Thi Thanh Huyen Kuala Lumpur, Malaysia, 30 June-3 July 2013

  2. BACKGROUND TB-HIV coinfection challenges: TB-Immune Reconstitution Inflammatory Syndrome (TB-IRIS) • Prognostic/diagnostic test: unavailable • Precise mechanisms: incompletely understood STUDY QUESTION What is the possible contribution of monocytes to the development of TB-IRIS? Inflammatory Symptoms TB - IRIS Non-IRIS Time on ART Week 2 Baseline

  3. BASIS OF THE STUDY Genome-wide microarray analysis: IRIS patients versus Controls Inflammatory Symptoms TB - IRIS Non-IRIS Time on ART Week 2 Baseline

  4. BASIS OF THE STUDYGenome-wide microarray analysis: IRIS patients versus Controls Changes in transcriptional response: detectable at baseline and more apparent at week 2 Week 2 Baseline PRINCIPAL COMPONENT ANALYSIS Differential expression cut-off (Quantile range 0,5%, p < 0.01) GENE SIGNATURES FOR CLASSIFICATION considerable value for prognosis and diagnosis 104 genes 42 genes Accuracy 94.44% Accuracy 94.44% 11 genes 14 genes

  5. BASIS OF THE STUDYPathway analysis: IRIS patients versus Controls Ingenuity Pathway Analysis Modulated pathways directed toward INFECTION AND INFLAMMATION Complement system – IAS 2012 (Tran et al., AIDS, 2013 – in press)

  6. CONCLUSION • Monocyte-associated genes which could be used as accurate classifiers at baseline and at the approximate time of IRIS, i.e. as respectively predictive and diagnostic features • Functional mapping indicated a potential functional contribution of monocytes/myeloid cells to the development of TB-IRIS

  7. HYPOTHESIS TB-IRIS development is characterized by a dysregulation in anti- and pro-inflammatory processes in monocytes

  8. THANK YOU FOR YOUR ATTENTION!

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