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)
TB - IRIS
Non-IRIS
Inflammatory Symptoms
Time on ART
Baseline
Week 2
Prognostic/diagnostic test: unavailable
Precise mechanisms: incompletely understood
STUDY QUESTION
What is the possible contribution of monocytes to the development of TB-IRIS?

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

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

5. BASIS OF THE STUDY Pathway 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!