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

Abstract

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.

A CD4+ TNF+ monofunctional memory T-cell response to BCG vaccination is associated with Mycobacterium tuberculosis infection in infants exposed to HIV

“…Given the reduced sensitivity of IGRAs in young children, we also measured non-IFN-γ cytokines (IL-2, IP10, TNF, IL-5, and IL-15) in QFT-Plus supernatants and found an additional 5·1% of infants with positive tests ( Table 1 , Supplemental Figure 1). 7 , 14 No TST positive infants were positive by QFT-Plus or non-IFN-γ cytokines, and only one QFT-Plus positive infant was also ESAT-6/CFP-10-specific non-IFN-γ cytokine positive.…”

“… 7 However, we improved detection of Mtb infection by measuring non-IFN-γ cytokines in QFT-Plus supernatants, capturing an additional 5·1% of infants with Mtb sensitisation at 14 months of age. 14 Measurement of non-IFN-γ cytokines as part of QFT-Plus testing is a strength of this study that allows for insights into Mtb infection in young children. Another limitation of this study is that we were not able to measure BCG viability directly in participants.…”

“…We measured IL-2, IP10, TNF, IL-5, and IL-15, cytokines which have shown promise in the diagnosis of Mtb infection in prior studies. 14 A test was considered positive if the following criteria were met: 1. TB1-nil >90th percentile for that cytokine and TB1-nil ≥25% of sample nil; and 2.…”

Improved Algorithm-Based Magnetic Resonance Images Combined with Computed Tomography in the Diagnosis of Acquired Immune Deficiency Syndrome Combined with Spinal Tuberculosis

“…Tuberculosis is the most common and most likely secondary infection, and it is also one of the longest causes of death of AIDS patients [5]. erefore, in recent years, the number of AIDS patients with spinal tuberculosis has gradually increased, and the corresponding diagnosis and treatment methods are different from single disease infection, and the main characteristics of the two diseases need to be considered [6][7][8][9]. Patients with combined disease mainly manifested as combined lung and extrapulmonary tuberculosis.…”