title: Natural killer cell degranulation capacity predicts early onset of the immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients with tuberculosis.
abstract: Immune reconstitution inflammatory syndrome (IRIS) is a common and potentially serious complication occurring in HIV-infected patients being treated for tuberculosis (TB) using combined antiretroviral treatment. A role of adaptive immunity has been suggested in the onset of IRIS, whereas the role of natural killer (NK) cells has not yet been explored. The present study sought to examine the involvement of NK cells in the onset of IRIS in HIV-infected patients with TB and to identify predictive markers of IRIS. A total of 128 HIV-infected patients with TB from the Cambodian Early versus Late Introduction of Antiretroviral Drugs (CAMELIA) trial were enrolled in Cambodia. Thirty-seven of the 128 patients developed IRIS. At inclusion, patients had low CD4 cell counts (27 cells/mm(3)) and high plasma viral load (5.76 and 5.50 log/mL in IRIS and non-IRIS patients, respectively). At baseline, NK-cell degranulation capacity was significantly higher in IRIS patients than in non-IRIS patients (9.6% vs 6.38%, P < .005). At IRIS onset, degranulation capacity did not differ between patients, whereas activating receptor expression was lower in IRIS patients. Patients with degranulation levels > 10.84% had a higher risk of IRIS (P = .002 by log-rank test). Degranulation level at baseline was the most important IRIS predictor (hazard ratio = 4.41; 95% confidence interval, 1.60-12.16). We conclude that NK-degranulation levels identify higher IRIS risk in HIV-infected patients with TB.
authors.affiliation: Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
authors.forename: Polidy
authors.initials: P
authors.lastname: Pean
authors.forename: Eric
authors.initials: E
authors.lastname: Nerrienet
authors.forename: Yoann
authors.initials: Y
authors.lastname: Madec
authors.forename: Laurence
authors.initials: L
authors.lastname: Borand
authors.forename: Didier
authors.initials: D
authors.lastname: Laureillard
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez
authors.forename: Olivier
authors.initials: O
authors.lastname: Marcy
authors.forename: Chan
authors.initials: C
authors.lastname: Sarin
authors.forename: Kerya
authors.initials: K
authors.lastname: Phon
authors.forename: Sylvia
authors.initials: S
authors.lastname: Taylor
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D015550:Cell Degranulation / Q000276:immunology*; D060085:Coinfection / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000150:complications / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D055607:Receptors, Natural Killer Cell / Q000378:metabolism; D014376:Tuberculosis / Q000150:complications / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D037181:Lectins, C-Type; D055607:Receptors, Natural Killer Cell; D000099192:CD69 Antigens