Molecular, Immunological, and Clinical Features of 16 Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease

Sarrafzadeh, Shokouh Azam; Nourizadeh, Maryam; Mahloojirad, Maryam; Fazlollahi, Mohammad Reza; Shoormasti, Raheleh Shokouhi; Badalzadeh, Mohsen; Deswarte, Caroline; Casanova, Jean‐Laurent; Pourpak, Zahra; Bustamante, Jacinta; Moin, Mostafa

doi:10.1007/s10875-019-0593-4

Cited by 14 publications

(4 citation statements)

References 30 publications

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“…Among the 19 causal genes of MSMD [ 4 ], this study described variant in three genes ( IL12RB1, IFNGR1 , and IFNGR2 ) that define four genetic disorders (AR IL-12Rβ1 deficiency, AR - complete IFN-gR1 deficiency, AD-partial IFN-gR1 deficiency, and AR-partial IFN-gR2 deficiency). One of the most frequent variants in IL12RB1 Mexican kindreds is c.1791 + 2 T > G, which is the most frequently reported mutation worldwide [ 21 , 33 ]. P10 had a compound heterozygous variant of IL12RB1 , c.635G > A, that was only recently reported (21) and c.1750C > T, which has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Hypersensitivity vasculitis is a rare manifestation occurring during an atypical mycobacterial infection in a healthy subject [ 32 , 33 ]. Furthermore, there are a few exceptional MSMD-deficient patients that presented with LCV, especially patients with IL-12Rβ1 deficiency [ 3 , 26 , 27 ]. Our review of 18 MSMD cases with vasculitis revealed that this complication appears in middle childhood in patients predominantly originated from Turkey.…”

Section: Discussionmentioning

confidence: 99%

Leukocytoclastic vasculitis in patients with IL12B or IL12RB1 deficiency: case report and review of the literature

et al. 2021

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Background Mendelian susceptibility to mycobacterial disease (MSMD) is an inborn error of immunity, resulting in susceptibility to weakly virulent mycobacteria and other intramacrophagic pathogens. Rheumatologic manifestations and vasculitis are considered rare manifestations in MSMD patients. Case presentation In this study, we reported a 20-year-old female who was presented with recurrent lymphadenitis following bacillus Calmette-Guérin (BCG) vaccination and a history of recurrent disseminated rash diagnosed as leukocytoclastic vasculitis (LCV). A slight reduction in lymphocyte subsets including CD4+, CD19+, and CD 16 + 56 T-cell count, as well as an elevation in immunoglobulins level (IgG, IgA, IgM, IgE), were observed in the patient. Whole exome sequencing revealed a homozygous Indel-frameshift mutation, c.527_528delCT (p. S176Cfs*12), at the exon 5 of the IL12B gene. She experienced symptom resolution after treatment with anti-mycobacterial agents and subcutaneous IFN-γ. We conducted a manual literature search for MSMD patients reported with vasculitis in PubMed, Web of Science, and Scopus databases. A total of 18 MSMD patients were found to be affected by a variety of vasculitis phenotypes mainly including LCV and Henoch-Schönlein purpura (HSP) with often skin involvement. Patients were all involved with vasculitis at the median age of 6.8 (2.6–7.7) years, nearly 6.1 years after the initial presentations. Sixteen patients (88.9%) had IL12RB1 defects and concurrent Salmonella infection was reported in 15 (88.2%) patients. Conclusion The lack of IL-12 and IL-23 signaling/activity/function and salmonella infection may be triggering factors for the development of leukocytoclastic vasculitis. IL12B or IL12RB1 deficiency and salmonellosis should be considered in MSMD patients with vasculitis.

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“…While frank deficiency of IFN-y (e.g., advanced AIDS) or its upstream or downstream signaling molecules predisposes to extrapulmonary visceral/disseminated NTM disease, several studies have found reduced IFN-y production from the peripheral blood mononuclear cells (PBMC) or whole blood from NTM lung disease patients [52,53], acknowledging that this is not seen by others [54]. More recently, decreased IFN-y gene expression in the whole blood of NTM lung disease patients compared to control subjects who had bronchiectasis/chronic obstructive pulmonary disease but no NTM infection.…”

Section: Host Immune Defects In Ntm Infection and Progressive Diseasementioning

confidence: 99%

Non-Tuberculous Mycobacteria Interference with BCG-Current Controversies and Future Directions

2020

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The global tuberculosis (TB) epidemic caused by the bacterial pathogen Mycobacterium tuberculosis (M.tb) continues unabated. The Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccination is widely utilized worldwide to protect against infection with M.tb. BCG vaccine protection against TB has had widely varying results for reasons that are not well understood. BCG vaccine interference by non-tuberculosis (NTM) mycobacterial species has been implicated as the potential cause of reduced BCG vaccine efficacy against M.tb. Ongoing efforts to develop new vaccines for TB requires a thorough understanding of the effect of NTM exposure on BCG vaccine efficacy, which may ultimately be a critical determinant of success. We reviewed the conflicting reports on whether NTM interferes with the BCG vaccine, potential explanations to help resolve the controversy, and strategies for developing better animal models. Further studies are needed to longitudinally track the effects of NTM exposure on BCG vaccine-induced host-protective anti-TB immunity.

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Molecular, Immunological, and Clinical Features of 16 Iranian Patients with Mendelian Susceptibility to Mycobacterial Disease

Cited by 14 publications

References 30 publications

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

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

Leukocytoclastic vasculitis in patients with IL12B or IL12RB1 deficiency: case report and review of the literature

Non-Tuberculous Mycobacteria Interference with BCG-Current Controversies and Future Directions

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