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. 2024 Mar 1;43(3):278-285.
doi: 10.1097/INF.0000000000004211. Epub 2023 Dec 18.

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis

Raquel Villar-Hernández  1   2   3   4 , Irene Latorre  1   2   3 , Antoni Noguera-Julian  5   6   7   8 , Aina Martínez-Planas  5   6 , Laura Minguell  9 , Teresa Vallmanya  9 , María Méndez  10 , Antoni Soriano-Arandes  11 , Fernando Baquero-Artigao  12   13 , Paula Rodríguez-Molino  12   13 , Sara Guillén-Martín  14 , Carlos Toro-Rueda  15 , M Luiza De Souza-Galvão  16 , M Ángeles Jiménez-Fuentes  16 , Zoran Stojanovic  2   17 , Josefina Sabriá  18 , José Ramón Santos  19 , Jordi Puig  19 , Marisol Domínguez-Álvarez  20 , Joan-Pau Millet  8   21 , Neus Altet  8   21 , Yolanda Galea  22 , Beatriz Muriel-Moreno  1   2   3 , Esther García-García  1   2   3 , Marc Bach-Griera  3 , Cristina Prat-Aymerich  1   2   3   23 , Esther Julián  3 , Jordi B Torrelles  24 , Carlos Rodrigo  10 , José Domínguez  1   2   3
Affiliations

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis

Raquel Villar-Hernández et al. Pediatr Infect Dis J. .

Abstract

Background: Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens.

Methods: We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay.

Results: NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group.

Conclusions: Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

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Conflict of interest statement

R.V.H., I.L., J.B.T. and J.D. are registered as inventors on a patent (WO 2019/234296 A1) filed by Institut d’Investigació Germans Trias i Pujol, CIBER, and The Ohio State University Innovation Foundation, disclosing the use of GPLs for NTM infection diagnosis. Such patent has been licensed by Genome Identification Diagnostics (GenID) GmbH. R.V.H. is currently employed by GenID but not at the moment this study was performed. I.L. is funded by the Miguel Servet programme, Instituto de Salud Carlos III (Spain). A.S.A. received funding from Fundació la Marató TV3 exp 202134-30-31 Projecte Escoles Sentinella (Departament de Salut i d’Educació de la Generalitat de Catalunya). F.B.A. has participated on Pfizer, Merck Sharp and Dohme (MSD) and Glaxo Smith Kline (GSK)’s Advisory Boards, has received honoraria for presentations from Pfizer and MSD and his institution receives payments from MSD and GSK. J.R.S. has received consulting fees, payment honoraria, payment for expert testimony and support attending meetings and/or travels from ViiV, Gilead and MSD. The other authors have no conflicts of interest to disclose.

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