Immune response to Mycobacterium tuberculosis in young contacts with discordant immunological test results

Jeljeli, Mohamed; Khourouj, Valérie Guérin-El; Pommelet, Virginie; Guilmin-Crépon, Sophie; Hormi, Myriam; Gressèns, Pierre; Faye, Albert; Sterkers, Ghislaine

doi:10.1016/j.jinf.2016.08.013

Cited by 3 publications

(5 citation statements)

References 7 publications

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“…The present study did not include a control group without M. tuberculosis infection, but the capability of multiplex based cytokine analysis to detect M. tuberculosis infection has been shown by others [13,[18][19][20][21]. In addition, we recently performed a pilot study in Germany of children with TB, latent M. tuberculosis infection, and noninfected controls [22].…”

Section: Discussionmentioning

confidence: 96%

Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana

Lundtoft

Awuah

Nausch

et al. 2017

Med Microbiol Immunol

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IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana. Concentrations of 18 cytokines in QFT supernatants from children (0-16 years) with tuberculosis concomitantly infected with HIV (n = 25) or without HIV (n = 24) from Ghana were measured using cytometric bead array (CBA). 29% of the children showed positive IFN-γ test results, and five cytokines, i.e., IL-6, IL-21, TNF-α, IL-1α and IP-10, detected M. tuberculosis infection with comparable or, for IL-6, with significantly higher sensitivity (59%). Increased age and HIV co-infection were associated with decreased cytokine induction, and especially IL-21 and IP-10 were less prevalent in HIV co-infected children with tuberculosis. Combined cytokine analyses increased proportions of positive tests, and a four-cytokine subset (i.e., IL-6, IL-21, IFN-γ, IL-1α) predicted 78% of the children with tuberculosis correctly. Combined evaluation of IFN-γ and alternative cytokines improved IGRA-sensitivity in children with tuberculosis.

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Section: Discussionmentioning

confidence: 96%

Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana

Lundtoft

Awuah

Nausch

et al. 2017

Med Microbiol Immunol

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“…In conclusion, although combining IL-13 and IP-10 may improve QFT sensitivity for diagnosing TB in immunocompetent young children [3], only IP-10 showed promise for improving TB diagnosis in HIV + children. Larger pediatric cohorts are warranted to investigate whether measuring IP-10 in combination with IFN- may improve QFT sensitivity without compromising specificity in HIV + /TB + children and invite to identify HIV + pediatric subgroups that could best benefit from IP-10 release implementation.…”

Section: Sirmentioning

confidence: 93%

“…In this journal, we recently reported the potential added value of combining IFNgamma, IP-10 and IL-13 releases for diagnosing latent TB in 0-5 years old immunocompetent children [3]. Here, we further explored the potential added value of these biomarkers in HIVinfected children.…”

Section: Sirmentioning

confidence: 99%

Cytokine/chemokine secretion for detecting tuberculosis in quantiferon supernatants from HIV + and HIV − children

Jeljeli

Khourouj

Pommelet

et al. 2017

Journal of Infection

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“…Presence of Mtb sensitization at birth, demonstrated in multiple studies, 34,[46][47][48][49] diagnostic results in infants and young children, is unknown. Mtb specific-antigen induced IFNγ, IP10 and TNF have been detected in cord blood at birth, regardless of maternal Mtb infection status; kinetics demonstrated that these cytokines increased over the first 24 weeks of life before plateauing and remained elevated at 1 year of age.…”

Section: Discussionmentioning

confidence: 99%

“…Presence of Mtb sensitization at birth, demonstrated in multiple studies, 34,46–49 may also confound interpretation of infant TST and ESAT6/CFP10 responses in evaluation for Mtb infection, even after 1 year of life. Infant ESAT6/CFP10 responses may be due to Mtb infection or maternal sensitization.…”

Section: Discussionmentioning

confidence: 99%

Non-IFNγ Whole Blood Cytokine Responses to Mycobacterium tuberculosis Antigens in HIV-exposed Infants

Anterasian

Warr

LaCourse

et al. 2021

Pediatric Infectious Disease Journal

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Background: HIV-exposed uninfected (HEU) infants have increased risk of tuberculosis (TB). Testing for Mycobacterium tuberculosis (Mtb) infection is limited by reduced Quantiferon (QFT) sensitivity in infants and tuberculin skin test (TST) cross-reactivity with Bacillus Calmette-Guérin vaccine. Our objective is to assess if non-IFNγ cytokine responses to Mtbspecific antigens have improved sensitivity in detecting Mtb infection in HEU infants compared with QFT. Methods: HEU infants were enrolled in a randomized clinical trial of isoniazid preventive therapy (IPT) to prevent Mtb infection in Kenya (N = 300) and assessed at 12 months postrandomization (14 months of age) by TST and QFT-Plus. Non-IFNγ cytokine secretion (IL2, TNF, IP10, N = 229) in QFT-Plus supernatants was measured using Luminex assay. Logistic regression was used to assess the effect of IPT on Mtb infection outcomes in HEU infants. Results: Three of 251 (1.2%) infants were QFT-Plus positive. Non-IFNγ Mtb antigen-specific responses were detected in 12 additional infants (12/229, 5.2%), all TST negative. IPT was not associated with Mtb infection defined as any Mtb antigen-specific cytokine response (odds ratio = 0.7, P = 0.54). Mtb antigen-specific IL2/IP10 responses had fair correlation (τ = 0.25). Otherwise, non-IFNγ cytokine responses had minimal correlation with QFT-Plus and no correlation with TST size. Conclusions:We detected non-IFNg Mtb antigen-specific T-cell responses in 14-month HEU infants. Non-IFNg cytokines may be more sensitive than IFNg in detecting infant Mtb infection. IPT during the first year of life was not associated with Mtb infection measured by IFNg, IL2, IP10 and TNF Mtb-specific responses.

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Immune response to Mycobacterium tuberculosis in young contacts with discordant immunological test results

Cited by 3 publications

References 7 publications

Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana

Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana

Cytokine/chemokine secretion for detecting tuberculosis in quantiferon supernatants from HIV + and HIV − children

Non-IFNγ Whole Blood Cytokine Responses to Mycobacterium tuberculosis Antigens in HIV-exposed Infants

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