TY - JOUR
T1 - The role of monocytes in the development of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome
AU - Tran, Huyen Thi Thanh
AU - van den Bergh, Rafael
AU - Vu, Trung Nghia
AU - Laukens, Kris
AU - Worodria, William
AU - Loembé, Marguerite Massinga
AU - Colebunders, Robert
AU - Kestens, Luc
AU - de Baetselier, Patrick
AU - Raes, Geert
AU - AUTHOR GROUP
AU - Mayanja-Kizza, Harriet
AU - Mascart, Françoise
AU - den Bergh, Rafaelvan
AU - Locht, Camille
AU - Reiss, Peter
AU - Cobelens, Frank
AU - Ondoa, Pascale
AU - Pakker, Nadine
AU - Mugerwa, Roy
PY - 2014
Y1 - 2014
N2 - Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication of combined antiretroviral therapy (cART) in HIV-TB co-infected patients. However, the disease mechanism is poorly understood, prognosis of TB-IRIS is currently impossible, and diagnosis is highly challenging. We analyzed whether the gene expression of monocytes could be correlated with TB-IRIS pathogenesis and could be used to classify patients predisposed to TB-IRIS. Monocyte gene expression was compared between patients who developed TB-IRIS and matched controls. We carried out whole-genome expression profiling using Affymetrix GeneChip(®) ST 1.1 arrays at two time-points: before cART initiation (baseline) and at week two post-cART initiation. For each time-point, we used different statistical approaches to identify molecular signatures which could be used as classifiers. We also functionally mapped the modulated cellular pathways using the software package Ingenuity Pathway Analysis. At baseline, before introduction of cART and before onset of symptoms, monocyte gene expression was already perturbed in patients who subsequently developed TB-IRIS, indicating a possible involvement of monocytes in TB-IRIS predisposition. The differences in monocyte gene expression in TB-IRIS patients became even more clear after two weeks of cART (when TB-IRIS commonly occurs), with more than 100 genes for which expression showed a fold change greater than 1.5. Both at baseline and at week two post-cART initiation, a classifier of 8 and 9 genes, respectively could be built, which allowed discrimination of TB-IRIS cases and controls. Pathway analyses revealed that the majority of the dysregulated genes in TB-IRIS - at the time of the IRIS episode, but also already at baseline - are associated with infection and inflammation. Relevant biological functions which were perturbed before/during TB-IRIS included "Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses" and "Complement System". Our results indicate an involvement of monocytes in predisposition to/development of TB-IRIS, and suggest a number of functional pathways which may play a role in TB-IRIS development. This comprehensive study of gene regulation in monocytes provides baseline data for further studies into biomarkers for prognosis and diagnosis of TB-IRIS
AB - Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication of combined antiretroviral therapy (cART) in HIV-TB co-infected patients. However, the disease mechanism is poorly understood, prognosis of TB-IRIS is currently impossible, and diagnosis is highly challenging. We analyzed whether the gene expression of monocytes could be correlated with TB-IRIS pathogenesis and could be used to classify patients predisposed to TB-IRIS. Monocyte gene expression was compared between patients who developed TB-IRIS and matched controls. We carried out whole-genome expression profiling using Affymetrix GeneChip(®) ST 1.1 arrays at two time-points: before cART initiation (baseline) and at week two post-cART initiation. For each time-point, we used different statistical approaches to identify molecular signatures which could be used as classifiers. We also functionally mapped the modulated cellular pathways using the software package Ingenuity Pathway Analysis. At baseline, before introduction of cART and before onset of symptoms, monocyte gene expression was already perturbed in patients who subsequently developed TB-IRIS, indicating a possible involvement of monocytes in TB-IRIS predisposition. The differences in monocyte gene expression in TB-IRIS patients became even more clear after two weeks of cART (when TB-IRIS commonly occurs), with more than 100 genes for which expression showed a fold change greater than 1.5. Both at baseline and at week two post-cART initiation, a classifier of 8 and 9 genes, respectively could be built, which allowed discrimination of TB-IRIS cases and controls. Pathway analyses revealed that the majority of the dysregulated genes in TB-IRIS - at the time of the IRIS episode, but also already at baseline - are associated with infection and inflammation. Relevant biological functions which were perturbed before/during TB-IRIS included "Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses" and "Complement System". Our results indicate an involvement of monocytes in predisposition to/development of TB-IRIS, and suggest a number of functional pathways which may play a role in TB-IRIS development. This comprehensive study of gene regulation in monocytes provides baseline data for further studies into biomarkers for prognosis and diagnosis of TB-IRIS
U2 - https://doi.org/10.1016/j.imbio.2013.07.004
DO - https://doi.org/10.1016/j.imbio.2013.07.004
M3 - Article
C2 - 23958034
SN - 0171-2985
VL - 219
SP - 37
EP - 44
JO - Immunobiology
JF - Immunobiology
IS - 1
ER -