Mendelian susceptibility to mycobacterial disease in tuberculosis-hyperendemic South Africa.
| Autor: | Cornelissen HM; Division of Haematopathology, National Health Laboratory Service and Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa. hcornelissen@sun.ac.za., Glanzmann B, Van Coller A, Engelbrecht C, Abraham DR, Reddy K, Möller M, Kinnear C, Glashoff RH, Esser M |
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| Jazyk: | angličtina |
| Zdroj: | South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde [S Afr Med J] 2021 Oct 05; Vol. 111 (10), pp. 998-1005. Date of Electronic Publication: 2021 Oct 05. |
| DOI: | 10.7196/SAMJ.2021.v111i10.15341 |
| Abstrakt: | Background: Severe infections in the absence of secondary immunodeficiency can alert clinicians to single-gene inborn errors of immunity/primary immunodeficiency disorders (PIDDs). Mendelian susceptibility to mycobacterial disease (MSMD) is characterised by selective susceptibility to mycobacterial infections due to inborn errors in the interleukin 12-interferon gamma pathway. The South African (SA) burden of hyperendemic tuberculosis (TB) infection provides an interesting context for the study of MSMD. Objectives: To evaluate whether severe, persistent, unusual or recurrent (SPUR) definitions of TB can be applied in the context of MSMD in SA. Methods: This study is a retrospective review of an SA PIDD cohort. Patients aged 0 - 15 years with SPUR TB infections, assessed between 2013 and 2018, were identified using a proposed algorithm. HIV infection or other secondary causes for immunodeficiency were excluded. Basic investigations, then focused immunophenotyping and next-generation sequencing, were performed. Results: A total of 20 patients with a clinical diagnosis of MSMD were identified. A further two, forming part of a family cohort, had pathogenic variants but remain asymptomatic. Infection with Mycobacterium tuberculosis complex predominated (64%), while 27% had BCG infection or non-tuberculous mycobacteria (NTM) infection. Molecular analysis revealed pathogenic variants in 41% of patients with SPUR mycobacterial infection, mainly in those with BCG/NTM infection. Conclusions: In the SA paediatric population, SPUR TB infections, particularly BCG/NTM, in the absence of secondary immunodeficiency, can alert to possible MSMD. The molecular diagnosis is pivotal, guiding disease classification and influencing clinical approach and management. The diagnosis is complex and requires a multidisciplinary approach with close collaboration between clinical immunologists, bioinformaticians, immunologists, clinical geneticists and genetic counsellors. |
| Databáze: | MEDLINE |
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