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11.01.2023 | Original Article

Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical, Immunological, and Genetic Features of 22 Patients from 15 Moroccan Kindreds

verfasst von: Abderrahmane Errami, Jamila El Baghdadi, Fatima Ailal, Ibtihal Benhsaien, Jalila El Bakkouri, Leila Jeddane, Noureddine Rada, Noufissa Benajiba, Khaoula Mokhantar, Kaoutar Ouazahrou, Sanae Zaidi, Laurent Abel, Jean-Laurent Casanova, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Ahmed Aziz Bousfiha

Erschienen in: Journal of Clinical Immunology | Ausgabe 4/2023

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Abstract

Purpose

The first molecular evidence of a monogenic predisposition to mycobacteria came from the study of Mendelian susceptibility to mycobacterial disease (MSMD). We aimed to study this Mendelian susceptibility to mycobacterial diseases in Moroccan kindreds through clinical, immunological, and genetic analysis.

Methods

Patients presented with clinical features of MSMD were recruited into this study. We used whole blood samples from patients and age-matched healthy controls. To measure IL-12 and IFN-γ production, samples were activated by BCG plus recombinant human IFN-γ or recombinant human IL-12. Immunological assessments and genetic analysis were also done for patients and their relatives.

Results

Our study involved 22 cases from 15 unrelated Moroccan kindreds. The average age at diagnosis is 4 years. Fourteen patients (64%) were born to consanguineous parents. All patients were vaccinated with the BCG vaccine, and twelve of them (55%) developed locoregional or disseminated BCG infections. The other symptomatic patients had severe tuberculosis and/or recurrent salmonellosis. Genetic mutations were identified on the following genes: IL12RB1 in 8 patients, STAT1 in 7 patients; SPPL2A, IFNGR1, and TYK2 in two patients each; and TBX21 in one patient, with different modes of inheritance. All identified mutations/variants altered production or response to IFN-γ or both.

Conclusion

Severe forms of tuberculosis and complications of BCG vaccination may imply a genetic predisposition present in the Moroccan population. In the presence of these infections, systematic genetic studies became necessary. BCG vaccination is contraindicated in MSMD patients and should be delayed in newborn siblings until the exclusion of a genetic predisposition to mycobacteria.

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Titel: Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical, Immunological, and Genetic Features of 22 Patients from 15 Moroccan Kindreds
verfasst von: Abderrahmane Errami
Jamila El Baghdadi
Fatima Ailal
Ibtihal Benhsaien
Jalila El Bakkouri
Leila Jeddane
Noureddine Rada
Noufissa Benajiba
Khaoula Mokhantar
Kaoutar Ouazahrou
Sanae Zaidi
Laurent Abel
Jean-Laurent Casanova
Stéphanie Boisson-Dupuis
Jacinta Bustamante
Ahmed Aziz Bousfiha
Publikationsdatum: 11.01.2023
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 4/2023
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-022-01419-x

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Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical, Immunological, and Genetic Features of 22 Patients from 15 Moroccan Kindreds

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