Circulating inflammatory biomarkers can predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome

被引：44

作者：

Haddow, Lewis J. ^{[1
,2
]}

Dibben, Oliver ^{[3
]}

Moosa, Mohamed-Yunus S. ^{[2
]}

Borrow, Persephone ^{[3
]}

Easterbrook, Philippa J. ^{[2
]}

机构：

[1] UCL, Div Infect Immun & Inflammatory Dis, Res Dept Infect & Populat Hlth, Ctr Sexual Hlth & HIV Res,Mortimer Market Ctr, London WC1E 6JB, England

[2] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Infect Dis, Durban, South Africa

[3] Univ Oxford, Nuffield Dept Clin Med, Jenner Inst, Oxford, England

来源：

AIDS | 2011年 / 25卷 / 09期

基金：

英国医学研究理事会;

关键词：

biomarker; chemokine; C-reactive protein; cytokine; HIV; immune reconstitution inflammatory syndrome; tuberculosis; ACTIVE ANTIRETROVIRAL THERAPY; CO-INFECTED PATIENTS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; RESTORATION-DISEASE; RISK-FACTORS; T-CELLS; CASE-DEFINITION; SOUTH-AFRICA; HIV; INITIATION;

D O I：

10.1097/QAD.0b013e3283477d67

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Objective: To identify inflammatory biomarker profiles during paradoxical and unmasking tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS), and determine whether differences in biomarkers prior to antiretroviral therapy (ART) predict subsequent development of TB-IRIS. Design: Case-control study within a cohort of patients initiating ART in South Africa (n = 498). Methods: Participants were followed up for 24 weeks for development of TB-IRIS. Plasma samples were collected at baseline and presentation with symptoms. Groups of cases and controls were as follows: pre-ART TB and developed paradoxical TB-IRIS (n = 9); pre-ART TB but no IRIS (n = 12); no pre-ART TB but developed unmasking TB-IRIS (n = 13); no pre-ART TB and no TB or IRIS during treatment (n = 12). Concentrations of 18 cytokines and chemokines, and C-reactive protein (CRP), were measured and compared. Results: Event samples were drawn a median of 28 days after ART initiation [interquartile range (IQR) 14-56 days]. During paradoxical TB-IRIS events, there were lower median concentrations of interleukin-10 [IL-10; 22.1 (IQR 15.3-34.9) vs. 82.2 (29.4-128.4) pg/ml, P = 0.047] and monocyte chemotactic protein-1 [MCP-1; 27.6 (20.0-29.7) vs. 71.4 (40.6-77.8) pg/ml, P = 0.005], and higher CRP : IL-10 ratio [2.2 x 10(3) (1.8-3.4) vs. 0.3 x 10(3) (0.2-0.5), P = 0.003] than in controls. Patients who developed unmasking TB-IRIS had higher median pre-ART levels of CRP [25 (8-47) vs. 6 (lower limit of detection, LLD-12) mg/l, P = 0.046] and interferon gamma (IFN-gamma) [9.1 (4.4-24.7) vs. 0.9 (LLD-8.7) pg/ml, P = 0.032] than controls. Conclusion: Patients with unmasking TB-IRIS had higher pre-ART levels of plasma IFN-gamma and CRP, consistent with preexisting subclinical TB. Paradoxical TB-IRIS was associated with lower levels of biomarkers of monocyte and regulatory T-cell activity, and higher CRP. (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

引用

页码：1163 / 1174

页数：12

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