1. Pag. Tran Thi Thanh Huyen – Vrije Universiteit Brussel - Belgium Washington, D.C., USA, 22-27 July 2012 Monocytes and the Complement System in TB-IRIS Tran Thi Thanh Huyen Vrije Universiteit Brussel BELGIUM Monocytes and the Complement System in TB-IRIS BACK GROUND TB-HIV coinfection challenges: TB-Immune Reconstitution Inflammatory Syndrome (TB-IRIS) TB - IRIS Non-IRIS Inflammatory Symptoms Time on ART Baseline Week 2 STUDY QUESTIONS What is the possible contribution of monocytes to the development of TB-IRIS? STUDY DESIGN Comparison of gene expression of monocytes in TB-IRIS v.s Non-TB-IRIS Genome-wide microarray analysis Focused gene expression profiling

2. Pag. Milestone of the study 2 MO gene profiles are different at both baseline and week 2 TB - IRIS Non-IRIS Inflammatory Symptoms Time on ART Baseline Week 2 Modulation of the complement system Classical pathway Lectin pathway Alternative pathway C1q C1r C1s C1-inh C1q + C1s-C1r-C1r-C1s = active C1 C1q mRNA: higher in TB-IRIS at both baseline and week 2 C1q C1r C1s C1-INH C1-INH + C1r-C1s ┤ C1q-C1r-C1s C1-INH mRNA and enzyme activity in TB-IRIS: Higher at baseline Decreased and equal to control at week 2

3. Pag. Hypothesis The development of TB-IRIS may depend on the relative balance between C1q and C1-INH BASELINE WEEK 2 Our transcriptome analysis Monocyte role in TB-IRIS aetiology Balance between C1q and C1-INH The innate immune system is an important driving force in the development of TB-IRIS. Conclusion