HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis
ABSTRACT Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is a serious health problem in Tunisia. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenit...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01638-23 |
| _version_ | 1797393627187511296 |
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| author | Soumaya Bchiri Asma Bouzekri Rym Ouni Rim Lahiani Emna Romdhane Neira Dekhil Sonia Ben Hamouda Helmi Mardassi Asma Ferjani Emanuelle Petit Véronique Corbière Soumaya Rammeh Françoise Mascart Camille Locht Mamia Ben Salah Mohamed Ridha Barbouche Chaouki Benabdessalem |
| author_facet | Soumaya Bchiri Asma Bouzekri Rym Ouni Rim Lahiani Emna Romdhane Neira Dekhil Sonia Ben Hamouda Helmi Mardassi Asma Ferjani Emanuelle Petit Véronique Corbière Soumaya Rammeh Françoise Mascart Camille Locht Mamia Ben Salah Mohamed Ridha Barbouche Chaouki Benabdessalem |
| author_sort | Soumaya Bchiri |
| collection | DOAJ |
| description | ABSTRACT Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is a serious health problem in Tunisia. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis (CNTL). Here, we evaluated the performance of heparin-binding hemagglutinin (HBHA) interferon-gamma (IFN-γ) release assay (IGRA) for the diagnosis of CTL. In addition, we evaluated granzyme B, granulysin, and perforin release assays as CTL biomarkers and assessed their potential contribution to improve HBHA-IGRA performance. Peripheral blood mononuclear cells from CTL-suspected patients were stimulated with HBHA, early secreted antigenic target 6 (ESAT-6), or purified protein derivative (PPD) for 24 h in the presence of IL-7. Cytotoxic mediators and IFN-γ release were assessed by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were used to evaluate the capacity of HBHA, ESAT-6, and PPD to discriminate between CTL (n = 27) and CNTL (n = 21). After applying bivariate and multivariate analyses, IFN-γ responses to HBHA appeared to offer the best distinction between CTL and CNTL, with an area under the curve of 0.9947, associated with 95.24% and 100% sensitivity and specificity, respectively. A principal component analysis showed clear clustering of the CTL versus the CNTL groups. This clustering was mainly attributed to HBHA-induced IFN-γ, PPD-induced granzyme B, and PPD-induced IFN-γ. These results thus suggest that the HBHA-IGRA provides high diagnostic accuracy for CTL versus CNTL, with high sensitivity and specificity. Combining HBHA-induced IFN-γ and PPD-induced granzyme B improves the accuracy to identify CTL. IMPORTANCE Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is currently a major health problem in Tunisia and in several regions around the world. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis. This study demonstrates the added value of the heparin-binding hemagglutinin-interferon-gamma release assay as an immunoassay in the context of CTL. |
| first_indexed | 2024-03-09T00:06:36Z |
| format | Article |
| id | doaj.art-bc79b7cde4dd4c32bf3482ecd57d7110 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-09T00:06:36Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-bc79b7cde4dd4c32bf3482ecd57d71102023-12-12T13:17:20ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.01638-23HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitisSoumaya Bchiri0Asma Bouzekri1Rym Ouni2Rim Lahiani3Emna Romdhane4Neira Dekhil5Sonia Ben Hamouda6Helmi Mardassi7Asma Ferjani8Emanuelle Petit9Véronique Corbière10Soumaya Rammeh11Françoise Mascart12Camille Locht13Mamia Ben Salah14Mohamed Ridha Barbouche15Chaouki Benabdessalem16Laboratory of Transmission, Control and Immunobiology of Infections, Pasteur Institute of Tunis , Tunis, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections, Pasteur Institute of Tunis , Tunis, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections, Pasteur Institute of Tunis , Tunis, TunisiaENT Department, Charles Nicolle Hospital , Tunis, TunisiaFaculty of Medicine of Tunis, University of Tunis El Manar , Tunis, TunisiaInstitut Pasteur de Tunis, University of Tunis El Manar , Tunis, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections, Pasteur Institute of Tunis , Tunis, TunisiaInstitut Pasteur de Tunis, University of Tunis El Manar , Tunis, TunisiaFaculty of Medicine of Tunis, University of Tunis El Manar , Tunis, TunisiaU-1019—CIIL-Center of Infection and Immunity of Lille, Univ Lille, CNRS, Inserm, Université de Lille, Institut Pasteur de Lille , Lille, FranceLaboratory of Vaccinology and Mucosal Immunity, Internal Medicine Department, Hôpital Universitaire de Bruxelles–CUB Hôpital Erasme, Université Libre de Bruxelles (U.L.B.) , Brussels, BelgiumFaculty of Medicine of Tunis, University of Tunis El Manar , Tunis, TunisiaLaboratory of Vaccinology and Mucosal Immunity, Internal Medicine Department, Hôpital Universitaire de Bruxelles–CUB Hôpital Erasme, Université Libre de Bruxelles (U.L.B.) , Brussels, BelgiumU-1019—CIIL-Center of Infection and Immunity of Lille, Univ Lille, CNRS, Inserm, Université de Lille, Institut Pasteur de Lille , Lille, FranceENT Department, Charles Nicolle Hospital , Tunis, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections, Pasteur Institute of Tunis , Tunis, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections, Pasteur Institute of Tunis , Tunis, TunisiaABSTRACT Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is a serious health problem in Tunisia. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis (CNTL). Here, we evaluated the performance of heparin-binding hemagglutinin (HBHA) interferon-gamma (IFN-γ) release assay (IGRA) for the diagnosis of CTL. In addition, we evaluated granzyme B, granulysin, and perforin release assays as CTL biomarkers and assessed their potential contribution to improve HBHA-IGRA performance. Peripheral blood mononuclear cells from CTL-suspected patients were stimulated with HBHA, early secreted antigenic target 6 (ESAT-6), or purified protein derivative (PPD) for 24 h in the presence of IL-7. Cytotoxic mediators and IFN-γ release were assessed by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were used to evaluate the capacity of HBHA, ESAT-6, and PPD to discriminate between CTL (n = 27) and CNTL (n = 21). After applying bivariate and multivariate analyses, IFN-γ responses to HBHA appeared to offer the best distinction between CTL and CNTL, with an area under the curve of 0.9947, associated with 95.24% and 100% sensitivity and specificity, respectively. A principal component analysis showed clear clustering of the CTL versus the CNTL groups. This clustering was mainly attributed to HBHA-induced IFN-γ, PPD-induced granzyme B, and PPD-induced IFN-γ. These results thus suggest that the HBHA-IGRA provides high diagnostic accuracy for CTL versus CNTL, with high sensitivity and specificity. Combining HBHA-induced IFN-γ and PPD-induced granzyme B improves the accuracy to identify CTL. IMPORTANCE Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is currently a major health problem in Tunisia and in several regions around the world. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis. This study demonstrates the added value of the heparin-binding hemagglutinin-interferon-gamma release assay as an immunoassay in the context of CTL.https://journals.asm.org/doi/10.1128/spectrum.01638-23tuberculosiscervical lymphadenitisdiagnosisbiomarkersHBHA |
| spellingShingle | Soumaya Bchiri Asma Bouzekri Rym Ouni Rim Lahiani Emna Romdhane Neira Dekhil Sonia Ben Hamouda Helmi Mardassi Asma Ferjani Emanuelle Petit Véronique Corbière Soumaya Rammeh Françoise Mascart Camille Locht Mamia Ben Salah Mohamed Ridha Barbouche Chaouki Benabdessalem HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis Microbiology Spectrum tuberculosis cervical lymphadenitis diagnosis biomarkers HBHA |
| title | HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis |
| title_full | HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis |
| title_fullStr | HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis |
| title_full_unstemmed | HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis |
| title_short | HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis |
| title_sort | hbha igra and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis |
| topic | tuberculosis cervical lymphadenitis diagnosis biomarkers HBHA |
| url | https://journals.asm.org/doi/10.1128/spectrum.01638-23 |
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