Markers indicate CD4 activation before TB IRIS in 69-person study
Markers of CD4-cell activation became elevated in patients who had TB immune reconstitution inflammatory syndrome (IRIS) after they began antiretroviral therapy (ART) for the first time. The ANRS 129 BKVIR team believes their findings “support a role for CD4+ T-cell activation prior to massive inflammation in the development of TB-IRIS.”
People starting ART with
Mycobacterium tuberculosis may experience paradoxical
worsening to TB symptoms, called IRIS. TB-IRIS may cause
significant morbidity and must be distinguished from TB
recurrence resulting from failing treatment.
ANRS investigators conducted this single-arm multicenter trial
to see whether changes in inflammatory biomarkers could
predict TB-IRIS. They monitored 26 plasma biomarkers through
the first 24 weeks of ART in people being treated for TB and
starting their first antiretroviral regimen.
TB-IRIS developed in 23 of 69 people (33%). Inflammatory
cytokines and chemokines interleukin (IL)-6, IL-8,
interferon-gamma-induced protein 10 (IP-10), and tumor
necrosis factor-alpha (TNF-α) all rose significantly at
ART week 4 in people with IRIS (P < 0.05 for each
marker).
Levels of the soluble IL-2 receptor sCD25, released upon
CD4-cell activation, was significantly higher at week 0 in
IRIS patients than in patients without IRIS (P <
0.05). sCD25 levels remained elevated in IRIS patients
throughout follow-up.
IL-7, a cytokine related to CD4-cell homeostasis, tended to be
higher in IRIS patients than non-IRIS patients. Higher
baseline levels of sCD25 and IL-7 each independently predicted
a shorter time to TB-IRIS (P = 0.005 and P =
0.02).
Source: Lisa A.
Chakrabarti, Céline Boucherie, Florence Bugault,
Marie-Christine Cumont, Caroline Roussillon, Guillaume Breton,
Olivier Patey, Geneviève Chêne, Laura Richert,
Olivier Lortholary. Biomarkers of CD4+ T-cell activation as
risk factors for tuberculosis-associated immune reconstitution
inflammatory syndrome. AIDS. 2014; 28:
1593-1602.
For the study abstract
(Downloading the complete article requires a
subscription to AIDS or an online payment; the
abstract is free.)
Source:
IAS
