Recurrent Salmonella Infections and Nephritis Complicating IgA Vasculitis in a Patient with IL-12Rβ1 Deficiency

Blancas-Galicia, Lizbeth; Peñafiel-Vicuña, A K; Scheffler‐Mendoza, Selma; Rojas-Maruri, M; Rivas-Larrauri, Francisco; Rodríguez-Lozano, Ana Luisa; Bustamante, Jacinta; Yamazaki‐Nakashimada, Marco Antonio

doi:10.18176/jiaci.0750

Cited by 3 publications

(7 citation statements)

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“…Health policies in countries where BCG is mandatory must include warning signs and/or screening for MSMD in children with an adverse reaction to the BCG vaccine. Patients deficient in IL-12Rβ1 are also susceptible to Salmonella infections, which are associated with recurrent leukocytoclastic vasculitis [12]. One patient in this study developed nephritis with recurrent leukocytoclastic vasculitis.…”

Section: Discussionmentioning

confidence: 61%

“…Genetic diagnosis was made using Sanger sequencing (P1-P7, P12-P14, P17-22), next-generation sequencing panel (P10-P11, P16), or whole-exome sequencing (WES) (P8-P9, P15) [5][6][7][8][9][10][11][12][13][14][15]. Deleterious variants identified by WES were confirmed by Sanger sequencing.…”

Section: Genetic Analysesmentioning

confidence: 99%

“…Pathogenic variants in MSMD genes were detected in all kindreds using Sanger sequencing (n = 10), copy number variants (n = 1), target gene sequencing panel (n = 3), and WES (n = 3) [5][6][7][8][9][10][11][12][13][14][15], affecting IL12RB1 in 13 kindreds (76%), IFNGR1 in 3 (18%), and IFNGR2 in one (6%) (Table 1). Biallelic variants in IL12RB1 were c.655A > T (p.S220C), c.402C > A (p.Y134*), c.517C > T (p.R173W), c.635G > A (p.R212Q), c.1456C > T (p.R486*), c.1561C > T (p.R521*), c.1750C > T (p.S584P), c.1791 + 2 T > G (p.A573Lfs*22), and deletion of exon 8 (designated △8) (Fig.…”

Section: Genetic Findings In 17 Msmd Kindredsmentioning

confidence: 99%

“…Microorganism isolation was negative; however, the patient responded well to antibiotic treatment. P12 had 30 episodes of septicemia caused by Salmonella group B, S. enterica serotype Typhi, S. choleraesius, and S. enteritidis, including recurrent Henoch-Schönlein purpura and arthritis, with renal biopsy showing IgA nephritis [12]. Considering a possible Salmonella carrier state [27], a cholecystectomy was performed; however, this did not improve the patient's condition.…”

Section: Salmonella and Other Bacterial Infections In Patients With Msmdmentioning

confidence: 99%

“…The severity and penetrance of MSMD are inversely correlated with residual IFN-γ activity [4]. In Mexico, only 11 cases of MSMD have been reported up to date [5][6][7][8][9][10][11][12][13][14][15][16]; the status of this IEI in different states is unknown [17]. This paper reports the genetic, immunological, and clinical features of the first cohort of MSMD patients from 10 hospitals in 4 states in Mexico.…”

Section: Introductionmentioning

confidence: 99%

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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: 61%

Section: Genetic Analysesmentioning

confidence: 99%

Section: Genetic Findings In 17 Msmd Kindredsmentioning

confidence: 99%

Section: Salmonella and Other Bacterial Infections In Patients With Msmdmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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High-throughput sequencing technologies in the detection of livestock pathogens, diagnosis, and zoonotic surveillance

Suminda

Bhandari

Won

et al. 2022

Computational and Structural Biotechnology Journal

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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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Recurrent Salmonella Infections and Nephritis Complicating IgA Vasculitis in a Patient with IL-12Rβ1 Deficiency

Abstract: Histological sections of the kidney. A) Photomicrography (4x) showing the presence of glomeruli with mesangial hyperplasia. B) Photomicrography (40x) showing mesangial hyperplasia, which is made evident with Masson's stain (C).

Cited by 3 publications

References 0 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

High-throughput sequencing technologies in the detection of livestock pathogens, diagnosis, and zoonotic surveillance

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

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