Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients

Mahdaviani, Seyed Alireza; Mansouri, Davood; Jamee, Mahnaz; Zaki‐Dizaji, Majid; Aghdam, Karim Rahimi; Mortaz, Esmail; Khorasanizadeh, MirHojjat; Eskian, Mahsa; Movahedi, Mahshid; Ghaffaripour, Hosseinali; Baghaie, Nooshin; Hassanzad, Maryam; Chavoshzadeh, Zahra; Mansouri, Mahboubeh; Mesdaghi, Mehrnaz; Ghaini, Mehdi; Noori, Farzad; Eskandarzadeh, Shabnam; Kahkooi, Shahram; Poorabdolah, Mihan; Tabarsi, Payam; Moniri, Afshin; Farnia, Parisa; Karimi, Abdollah; Boisson–Dupuis, Stéphanie; Rezaei, Nima; Marjani, Majid; Casanova, Jean‐Laurent; Bustamante, Jacinta; Velayati, Ali Akbar

doi:10.1007/s10875-020-00813-7

Cited by 26 publications

(14 citation statements)

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“…1A). P1 and P2 from kindred A, reported in previous studies ( 11 , 22 ), are homozygous for the c.344G>A missense variant, which results in the p.C115Y substitution in a key domain of IL-23R (Fig. 1B) ( 11 , 53 ).…”

Section: Resultsmentioning

confidence: 74%

Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria

et al. 2023

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Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 deficiency display Mendelian susceptibility to mycobacterial disease (MSMD) due to impaired IFN-γ production and, less commonly, chronic mucocutaneous candidiasis (CMC) due to impaired IL-17A/F production. We report six patients from four kindreds with AR IL-23R deficiency. These patients are homozygous for one of four different loss-of-function IL23R variants. All six patients have a history of MSMD, but only two suffered from CMC. We show that IL-23 induces IL-17A only in MAIT cells, possibly contributing to the incomplete penetrance of CMC in patients unresponsive to IL-23. By contrast, IL-23 is required for both baseline and Mycobacterium -inducible IFN-γ immunity in both Vδ2 + γδ T and MAIT cells, probably contributing to the higher penetrance of MSMD in these patients. Human IL-23 appears to contribute to IL-17A/F–dependent immunity to Candida in a single lymphocyte subset but is required for IFN-γ–dependent immunity to Mycobacterium in at least two lymphocyte subsets.

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Section: Resultsmentioning

confidence: 74%

Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria

et al. 2023

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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: 72%

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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“…A total number of twenty-four MSMD patients with BCG-osis or BCG-itis were enrolled in the study from 2009 to 2020. Fifteen patients (P1-P15) were reported in our previous study [ 18 ]. The male–female ratio was 1:1 and the median (IQR) age at the time of the study was 9.8 (6.7–12.0) years.…”

Section: Resultsmentioning

confidence: 99%

Effective anti-mycobacterial treatment for BCG disease in patients with Mendelian Susceptibility to Mycobacterial Disease (MSMD): a case series

Mahdaviani

Fallahi

Jamee

et al. 2022

Ann Clin Microbiol Antimicrob

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Background Post-vaccination BCG disease typically attests to underlying inborn errors of immunity (IEIs), with the highest rates of complications in patients with Mendelian susceptibility to mycobacterial disease (MSMD). However, therapeutic protocols for the management of BCG-osis (disseminated) and persistent BCG-itis (localized) are still controversial. Methods Twenty-four Iranian patients with MSMD (BCG-osis or BCG-itis), followed from 2009 to 2020 in Tehran, were included in the study. Their medical records were retrospectively reviewed for demographics, clinical features, laboratory findings, and molecular diagnosis. The therapeutic protocol sheets were prepared to contain the types and duration of anti-mycobacterial agents. Results BCG disease either as BCG-itis (33.3%) or BCG-osis (66.7%) was confirmed in all patients by positive gastric washing test (54.2%), microbial smear and culture (58.3%), or purified protein derivative (PPD) test (4.2%). The duration between BCG-osis onset and MSMD diagnosis was 21.6 months. All except three patients were initiated on second-line anti-mycobacterial agents with either a fluoroquinolone (levofloxacin: 15 mg/kg/day, ciprofloxacin: 20 mg/kg/day, ofloxacin: 15 mg/kg/day), aminoglycoside (amikacin: 10–15 mg/kg/day, streptomycin: 15 mg/kg/day), and/or macrolide (clarithromycin: 15 mg/kg/day) along with oral rifampin (10 mg/kg/day), isoniazid (15 mg/kg/day), and ethambutol (20 mg/kg/day). Three patients showed a clinical response to rifampin, despite in vitro resistance. Fourteen (58.3%) patients received also adjuvant subcutaneous IFN-γ therapy, 50 µ/m2 every other day. At the end of survey, most patients (n = 22, 91.7%) were alive and two patients died following BCG-osis and respiratory failure. Conclusions We recommend the early instigation of second-line anti-mycobacterial agents in MSMD patients with BCG disease.

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Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients

Cited by 26 publications

References 50 publications

Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria

Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria

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

Effective anti-mycobacterial treatment for BCG disease in patients with Mendelian Susceptibility to Mycobacterial Disease (MSMD): a case series

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