Proportions of interferon-γ-producing ascites lymphocytes in response to mycobacterial antigens: A help for early diagnosis of peritoneal tuberculosis in a low TB incidence country

Sophie Henrard 1 Véronique Corbière 2 Liliane Schandené 3 Martine Ducarme 3 Anne van Praet 2 Emmanuelle Petit 4 Mahavir Singh 5 Camille Locht 4 Violette Dirix 2 Françoise Mascart 2, 3, *
* Corresponding author
1 Immunodeficiencies Treatment Unit [Bruxelles, Belgique]
2 Laboratory of Vaccinology and Mucosal Immunity [Bruxelles, Belgique]
3 Immunobiology Clinic [Bruxelles, Belgique]
4 CIIL - Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204
5 Lionex Diagnostics and Therapeutics [Brunswick, Allemagne]
Abstract : BACKGROUND: Peritoneal tuberculosis (TB) remains difficult to diagnose because of its non-specific clinical features and the lack of efficient microbiological tests. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are needed. METHODS AND FINDINGS: We investigated for 24 patients prospectively enrolled with a possible diagnosis of peritoneal TB, the diagnostic value of the analysis of IFN-γ production by peritoneal fluid lymphocytes in response to a short in vitro stimulation with mycobacterial antigens. The patients were classified in two groups: non-TB and confirmed or highly probable TB. Diagnosis of TB was based on microbiological and histopathological criteria and/or a favorable response to anti-TB treatment. The IFN-γ production by peritoneal CD4+ T lymphocytes was analyzed by flow cytometry after an overnight in vitro stimulation with three different mycobacterial antigens, purified protein derivative (PPD), heparin-binding haemagglutinin (HBHA) or early-secreted-antigen-target-6 (ESAT-6). The percentages of PPD-, HBHA- or ESAT-6-induced IFN-γ-producing peritoneal fluid CD4+ T lymphocytes were higher in the TB group than in the non-TB group (p = 0.0007, p = 0.0004, and p = 0.0002 respectively). Based on cut-off values determined by ROC curve analysis of the results from TB and highly probable TB compared to those of non-TB patients, the sensitivity of these three tests was 100% with a specificity of 92%. CONCLUSIONS: The analysis of mycobacterial-induced IFN-γ production by peritoneal lymphocytes is a promising tool to reliably and rapidly diagnose peritoneal TB. Further studies should be performed on larger cohorts of patients in high-TB-incidence countries to confirm the clinical value of this new diagnostic approach for peritoneal TB.
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Sophie Henrard, Véronique Corbière, Liliane Schandené, Martine Ducarme, Anne van Praet, et al.. Proportions of interferon-γ-producing ascites lymphocytes in response to mycobacterial antigens: A help for early diagnosis of peritoneal tuberculosis in a low TB incidence country. PLoS ONE, Public Library of Science, 2019, 14 (4), pp.e0214333. ⟨10.1371/journal.pone.0214333⟩. ⟨inserm-02263536⟩

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