Browsing by Author "Ruiz-Tagle Seguel, Cinthya Grace"

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    Differential levels of anti-Mycobacterium tuberculosis-specific IgAs in saliva of household contacts with latent tuberculosis infection
    (FRONTIERS MEDIA SA, 2023) Ruiz-Tagle Seguel, Cinthya Grace; Naves Pichuante, Rodrigo Antonio; Garcia Canete, Patricia Del Carmen; Guenther, Anna; Schneiderhan-Marra, Nicole; Balcells Marty, Maria Elvira
    Introduction: Mucosal immunity is strongly elicited in early stages of many respiratory and enteric infections; however, its role in tuberculosis pathogenesis has been scarcely explored. We aimed to investigate Mycobacterium tuberculosis (Mtb) specific IgA levels in saliva in different stages of latent Tuberculosis Infection (TBI).Methodology: A multiplex bead-based Luminex immunoassay was developed to detect specific IgA against 12 highly immunogenic Mtb antigens. A prospective cohort of household contacts (>14 years) of pulmonary TB cases was established in Santiago, Chile. Contacts were classified as Mtb-infected or not depending on serial interferon-gamma release assay results. Saliva samples were collected and tested at baseline and at a 12-week follow-up.Results: Mtb-specific IgA was detectable at all visits in all participants (n = 168), including the "non-Mtb infected" (n = 64). Significantly higher median levels of IgA were found in the "Mtb infected" compared to the uninfected for anti-lipoarabinomannan (LAM) (110 vs. 84.8 arbitrary units (AU), p < 0.001), anti-PstS1 (117 vs. 83 AU, p < 0.001), anti-Cell Membrane Fraction (CMF) (140 vs. 103 AU, p < 0.001) and anti-Culture Filtrate Proteins (CFP) (median 125 vs. 96 AU, p < 0.001), respectively. Nonetheless, the discriminatory performance of these specific mucosal IgA for TBI diagnosis was low.Conclusion: Saliva holds Mtb-specific IgA against several antigens with increased levels for anti-LAM, anti-PstS1, anti-CMF and anti-CFP found in household contacts with an established TBI. The role of these mucosal antibodies in TB pathogenesis, and their kinetics in different stages of Mtb infection merits further exploring.
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    Evaluation of concordance of new QuantiFERON-TB Gold Plus platforms for Mycobacterium tuberculosis infection diagnosis in a prospective cohort of household contacts
    (2024) Ruiz-Tagle Seguel, Cinthya Grace; García Cañete, Patricia Del Carmen; Hernández, Mariluz; Balcells Marty, María Elvira
    Interferon-gamma (IFN-γ) release assays play a pivotal role in tuberculosis infection (TBI) diagnosis, with QuantiFERON-TB Gold Plus—an enzyme-linked immunosorbent assay (ELISA)—among the most widely utilized. Newer QuantiFERON-TB platforms with shorter turnaround times were recently released. We aimed to evaluate these platforms’ agreement in the diagnosis of TBI. Blood samples from a prospective cohort of tuberculosis household contacts were collected at baseline and after 12 weeks of follow-up, and tested with LIAISON, an automated chemiluminescence immunoassay (CLIA) system, QIAreach, a lateral flow (QFT-LF) semi-automated immunoassay, and the ELISA QuantiFERON-TB Gold Plus platform. Test concordances were analyzed. ELISA vs CLIA overall agreement was 83.3% for all tested samples (120/144) [Cohen’s kappa coefficient (κ): 0.66 (95% CI: 0.54–0.77)]. Samples positive with CLIA provided consistently higher IFN-γ levels than with ELISA (P < 0.001). Twenty-four (16.7%) discordant pairs were obtained, all CLIA-positive/ELISA-negative: 15 (62.5%) had CLIA IFN-γ levels within borderline values (0.35–0.99 IU/mL) and 9 (37.5%) >0.99 IU/mL. QFT-LF showed only 76.4% (68/89) overall agreement with ELISA [κ: 0.53 (95% CI: 0.37–0.68)] with 21 (23.6%) discordant results obtained, all QFT-LF-positive/ELISA-negative. Overall concordance between ELISA and CLIA platforms was substantial, and only moderate between ELISA and QFT-LF. The CLIA platform yielded higher IFN-γ levels than ELISA, leading to an almost 17% higher positivity rate. The techniques do not seem interchangeable, and validation against other gold standards, such as microbiologically-confirmed tuberculosis disease, is required to determine whether these cases represent true new infections or whether CLIA necessitates a higher cutoff.
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    Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile
    (Oxford University Press for the Infectious Diseases Society of America, 2022) Balcells Marty, María Elvira; Le Corre Pérez, Monique Nicole; Durán Santa Cruz, Josefina Gracia; Ceballos Valdivielso, María Elena Andrea; Vizcaya Altamirano, María Cecilia; Mondaca Contreras, Sebastián Patricio; Dib Marambio, Martin Javier; Rabagliati Borie, Ricardo Miguel; Sarmiento Maldonado, Mauricio; Burgos Cañete, Paula Isabel; Espinoza Sepúlveda, Manuel Antonio; Ferres Garrido, Marcela Viviana; Martínez Valdebenito, Constanza Pamela; Ruiz-Tagle Seguel, Cinthya Grace; Ortiz Koh, Catalina Alejandra; Ross Pérez, Patricio Daniel; Budnik Bitran, Sigall; Solari Gajardo, Sandra; Vizcaya Vergara, María De Los Ángeles; Lembach, Hanns; Berríos Rojas, Roslye; Melo González, Felipe; Rios Raggio, Mariana; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan Marcela; Nervi Nattero, Bruno
    Background Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. Methods This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. Results NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (PP = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon gamma spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. Conclusions Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients.
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    Reduced microbial diversity of the nasopharyngeal microbiome in household contacts with latent tuberculosis infection
    (NATURE PORTFOLIO, 2023) Ruiz-Tagle Seguel, Cinthya Grace; Ugalde, Juan A.; Naves Pichuante, Rodrigo Antonio; Araos, Rafael; Garcia Canete, Patricia Del Carmen; Balcells Marty, Maria Elvira
    The upper respiratory tract is an obliged pathway for respiratory pathogens and a healthy microbiota may support the host's mucosal immunity preventing infection. We analyzed the nasopharyngeal microbiome in tuberculosis household contacts (HHCs) and its association with latent tuberculosis infection (TBI). A prospective cohort of HHCs was established and latent TBI status was assessed by serial interferon-& gamma; release assay (IGRA). Nasopharyngeal swabs collected at baseline were processed for 16S rRNA gene sequencing. The 82 participants included in the analysis were classified as: (a) non-TBI [IGRA negative at baseline and follow-up, no active TB (n = 31)], (b) pre-TBI [IGRA negative at baseline but converted to IGRA positive or developed active TB at follow-up (n = 16)], and (c) TBI [IGRA positive at enrollment (n = 35)]. Predominant phyla were Actinobacteriota, Proteobacteria, Firmicutes and Bacteroidota. TBI group had a lower alpha diversity compared to non-TBI (p(adj) = 0.04) and pre-TBI (p(adj) = 0.04). Only TBI and non-TBI had beta diversity differences (p(adj) = 0.035). Core microbiomes' had unique genera, and genus showed differential abundance among groups. HHCs with established latent TBI showed reduced nasopharyngeal microbial diversity with distinctive taxonomical composition. Whether a pre-existing microbiome feature favors, are a consequence, or protects against Mycobacterium tuberculosis needs further investigation.