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Tran Thi Thanh Huyen – Vrije Universiteit Brussel - Belgium

BACK GROUND TB-HIV coinfection challenges: TB-Immune Reconstitution Inflammatory Syndrome (TB-IRIS). STUDY DESIGN Comparison of gene expression of monocytes in TB-IRIS v.s Non-TB-IRIS. Monocytes and the Complement System in TB-IRIS. Monocytes and the Complement System in TB-IRIS.

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Tran Thi Thanh Huyen – Vrije Universiteit Brussel - Belgium

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

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

  3. Hypothesis Conclusion The development of TB-IRIS may depend on the relative balance between C1q and C1-INH • 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. BASELINE WEEK 2

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