Tuberculosis after commencing antiretroviral therapy for HIV infection is associated with elevated CXCL9 and CXCL10 responses to Mycobacterium tuberculosis antigens.
BACKGROUND
Commencing antiretroviral therapy (ART) in human immunodeficiency virus-infected patients with treated or unrecognized Mycobacterium tuberculosis disease may trigger tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) or ART-associated tuberculosis (ART-TB). We have shown that whole-blood interferon-gamma release assays may aid in the prediction and diagnosis of ART-TB. Here, we investigate interferon-gamma-inducible chemokines CXCL9 and CXCL10.


METHODS
CXCL9 and CXCL10 responses to region of difference 1 (RD1) antigens and purified protein derivative (PPD) were assayed in plasma from whole-blood cultures collected before and after 4, 12, and 24 weeks of ART from 15 TB-IRIS cases, 11 ART-TB cases, and matched controls.


RESULTS
Relative to matched controls, ART-TB cases had elevated CXCL10 responses to RD1 antigens pre-ART (P = 0.02) and to PPD and RD1 antigens over 24 weeks of ART (P ≤ 0.02 and P ≤ 0.03). In contrast, TB-IRIS cases had higher CXCL10 responses to RD1 antigens before and after 4 weeks of ART only (P = 0.04 for both). CXCL9 responses to PPD and RD1 antigens were similar but less pronounced in ART-TB cases and did not differ between TB-IRIS cases and controls. CXCL10 responses to RD1 antigens performed as well as, or better than, IFN-γ responses in the prediction and diagnosis of ART-TB.


CONCLUSIONS
Tuberculosis after commencing ART is associated with increased CXCL10 and, to a lesser extent, CXCL9 responses to M. tuberculosis antigens. Assessment of antigen-induced CXCL10 responses to RD1 antigens may assist in the prediction and diagnosis of ART-TB.
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
Benjamin G
BG
Oliver
Julian H
JH
Elliott
Patricia
P
Price
Michael
M
Phillips
David A
DA
Cooper
Martyn A
MA
French
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology*; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000097:blood / Q000276:immunology*; D054370:Chemokine CXCL9 / Q000097:blood / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014376:Tuberculosis / Q000150:complications / Q000209:etiology* / Q000276:immunology
D019380:Anti-HIV Agents; D000942:Antigens, Bacterial; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C072681:Mycobacterium tuberculosis antigens