The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals

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• 作者：Desta Kassa^a ; ^b ; ^{dkassa2003@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Wilco de Jager^c ; ^{wjager@umcutrecht.nl" class="auth_mail" title="E-mail the corresponding author} ; Gebremedhin Gebremichael^a ; ^{gereachem@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Yodit Alemayehu^a ; ^{yudanet@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Leonie Ran^b ; ^{leonie.ran@roche.com" class="auth_mail" title="E-mail the corresponding author} ; Justin Fransen^b ; ^{j.h.fransen@umcutrecht.nl" class="auth_mail" title="E-mail the corresponding author} ; Dawit Wolday^d ; ^{dawwol@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Tsehaynesh Messele^a ; ^{tmessele@aslm.org" class="auth_mail" title="E-mail the corresponding author} ; Belete Tegbaru^a ; ^{bt2362@columbia.edu" class="auth_mail" title="E-mail the corresponding author} ; Tom H.M. Ottenhoff^e ; ^{T.H.M.Ottenhoff@lumc.nl" class="auth_mail" title="E-mail the corresponding author} ; Debbie van Baarle^b ; ¹ ; ^{debbie.van.baarle@rivm.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HIV/AIDS ; Tuberculosis ; Cytokines ; Biomarkers
• 刊名：Tuberculosis
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：96
• 期：Complete
• 页码：131-140
• 全文大小：1874 K

文摘

Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB.

Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV⁺TB⁺), HIV negative TB patients (HIV⁻TB⁺), HIV positive tuberculin skin test positive (TST+) (HIV⁺TST⁺), HIV negative TST+ (HIV⁻TST⁺), and HIV⁻TST⁻ individuals.

Compared to HIV⁻TST⁻, latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV⁻TST⁺ individuals compared to HIV⁻TB⁺ patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV⁻TB⁺ patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV⁺TB⁺ patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV⁺TST⁺ patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed.

In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART.