Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

Taur, Prasad; Gowri, Vijaya; Pandrowala, Ambreen; Iyengar, Vaishnavi V.; Chougule, Akshaya; Golwala, Zainab; Chandak, Shraddha; Agarwal, Reepa; Keni, Purva; Dighe, Neha; Bodhanwala, Minnie; Prabhu, Sunil; George, Biju; Na, Fouzia; Edison, Eunice Sindhuvi; Arunachalam, Arun Kumar; Madkaikar, Manisha; Dalvi, Aparna; Yadav, Reetika Malik; Bargir, Umair Ahmed; Kambli, Priyanka; Rawat, Amit; Das, Jhumki; Joshi, Vibhu; Pilania, Rakesh Kumar; Jindal, Ankur Kumar; Bhat, Sunil; Bhattad, Sagar; Unni, Jeeson; Radhakrishnan, Nita; Raj, Revathi; Uppuluri, Ramya; Patel, S. M.; Lashkari, Harsha Prasada; Aggarwal, Amita; Kalra, Manas; Udwadia, Zarir; Bafna, Vineet; Kanade, Tarun; Puel, Anne; Bustamante, Jacinta; Casanova, Jean Laurent; Desai, Mukesh

doi:10.3389/fimmu.2021.631298

Cited by 39 publications

(29 citation statements)

References 37 publications

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“…The first demonstration that genetic defects may contribute to severe mycobacterial infections in humans involved the identification of molecular defects in the IL-12/IFN-γ dependent signalling pathway in patients with Mendelian susceptibility to mycobacterial diseases (MSMD). MSMD is a group of complete or partial primary immunodeficiencies characterized by impaired IFN-γ-mediated immunity [171,172]. In MSMD-affected individuals, weakly virulent mycobacteria are responsible for severe infections [173].…”

Section: Implications Of Cytokine Receptor Gene Defects For the Cours...mentioning

confidence: 99%

Cytokine Receptors—Regulators of Antimycobacterial Immune Response

Druszczyńska

Godkowicz

Kulesza

et al. 2022

IJMS

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Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of immune cells during infection. They recognize and bind specific cytokines and are involved in inducing intracellular signal transduction pathways that regulate a diverse range of biological functions, including proliferation, differentiation, metabolism and cell growth. Due to mutations in cytokine receptor genes, defective signaling may contribute to increased susceptibility to mycobacteria, allowing the pathogens to avoid killing and immune surveillance. This paper provides an overview of cytokine receptors important for the innate and adaptive immune responses against mycobacteria and discusses the implications of receptor gene defects for the course of mycobacterial infection.

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Section: Implications Of Cytokine Receptor Gene Defects For the Cours...mentioning

confidence: 99%

Cytokine Receptors—Regulators of Antimycobacterial Immune Response

Druszczyńska

Godkowicz

Kulesza

et al. 2022

IJMS

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“…We aimed to improve the diagnosis of PTB in immunocompromised patients using the mNGS approach. Conversely, whole-genome sequencing (WGS) has been used to identify Mycobacterium abscessus (Bryant et al, 2013;Sassi and Drancourt, 2014;Harris et al, 2015) and Mycobacterium avium (Operario et al, 2019), and few case reports (He et al, 2020;Taur et al, 2021) and cases (Huang et al, 2019) have described NTM determination using mNGS. More importantly, there is no previous study on the identification of MTB and NTM in patients with unexplained pulmonary infection with AFS negative sputum smear using mNGS.…”

Section: Introductionmentioning

confidence: 99%

Next-Generation Metagenome Sequencing Shows Superior Diagnostic Performance in Acid-Fast Staining Sputum Smear-Negative Pulmonary Tuberculosis and Non-tuberculous Mycobacterial Pulmonary Disease

Yang

et al. 2022

Front. Microbiol.

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In this study, we explored the clinical value of next-generation metagenome sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) samples from patients with acid-fast staining (AFS) sputum smear-negative pulmonary tuberculosis (PTB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD). Data corresponding to hospitalized patients with pulmonary infection admitted to the hospital between July 2018 and July 2021, who were finally diagnosed with AFS sputum smear-negative PTB and NTM-PD, were retrospectively analyzed. Bronchoscopy data as well as mNGS, Xpert, AFS (BALF analysis), and T-SPOT (blood) data, were extracted from medical records. Thereafter, the diagnostic performances of these methods with respect to PTB and NTM-PD were compared. Seventy-one patients with PTB and 23 with NTM-PD were included in the study. The sensitivities of mNGS, Xpert, T-SPOT, and AFS for the diagnosis of PTB were 94.4% (67/71), 85.9% (61/71), 64.8% (46/71), and 28.2% (20/71), respectively, and the diagnostic sensitivity of mNGS combined with Xpert was the highest (97.2%, 67/71). The specificity of Xpert was 100%, while those of AFS and T-SPOT were 73.9% (17/23) and 91.3% (21/23), respectively. Further, the 23 patients with NTM-PD could be identified using mNGS, and in the population with immunosuppression, the sensitivities of mNGS, Xpert, T-SPOT, and AFS were 93.5% (29/31), 80.6% (25/31), 48.4% (15/31), and 32.3% (10/31), respectively, and the diagnostic sensitivity of mNGS combined with Xpert was the highest (100%, 31/31). The specificities of Xpert and T-SPOT in this regard were both 100%, while that of AFS was 40% (2/5). Furthermore, using mNGS, all the NTM samples could be identified. Thus, the analysis of BALF samples using mNGS has a high accuracy in the differential diagnosis of MTB and NTM. Further, mNGS combined with Xpert can improve the detection of MTB, especially in AFS sputum smear-negative samples from patients with compromised immune states or poor responses to empirical antibiotics.

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“…Similar to other countries, BCG vaccination is mandatory in Mexico [3,[35][36][37][38]. In this study, M. bovis-BCG was the main infectious agent in patients with MSMD, resulting in BCG being the principal cause of morbidity and mortality.…”

Section: Discussionmentioning

confidence: 73%

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico

Lara¹,

Nakashimada²,

León-Lara³

et al. 2022

J Clin Immunol

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Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis -Bacillus Calmette–Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella , as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 ( n = 13), IFNGR1 ( n = 3), and IFNGR2 ( n = 1) genes. Interleukin-12Rβ1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-022-01357-8.

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Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

Cited by 39 publications

References 37 publications

Cytokine Receptors—Regulators of Antimycobacterial Immune Response

Cytokine Receptors—Regulators of Antimycobacterial Immune Response

Next-Generation Metagenome Sequencing Shows Superior Diagnostic Performance in Acid-Fast Staining Sputum Smear-Negative Pulmonary Tuberculosis and Non-tuberculous Mycobacterial Pulmonary Disease

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico

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