Infectious diseases, autoimmunity and midline defect in a patient with a novel bi-allelic mutation in IL12RB1 gene

Göktürk, Bahar; Reisli, İsmail; Çalışkan, Ümran; Oleaga-Quintas, Carmen; Deswarte, Caroline; Turul-Özgür, Tuba; Burgucu, Durmuş; Migaud, Mélanie; Casanova, Jean‐Laurent; Pïcard, Capucine; Bustamante, Jacinta

doi:10.24953/turkjped.2016.03.019

Cited by 16 publications

(11 citation statements)

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“…Since the discovery of its first genetic etiology in 1996, MSMD has been reported and a causal genetic lesion described in 501 individuals from 356 kindreds originating from 57 countries on five continents (Figure a). Over this period, the genetic dissection of MSMD in these patients has revealed this condition to be caused by inborn errors of interferon (IFN)‐γ immunity . These findings confirm that IFN‐γ, first described in 1965 as an antiviral IFN, is actually the macrophage‐activating factor, as shown in 1983 .…”

Section: Introductionsupporting

confidence: 61%

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

et al. 2018

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Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-c immunity. Since 1996, disease-causing mutations have been found in 11 genes, which, through allelic heterogeneity, underlie 21 different genetic disorders. We briefly review here progress in the study of molecular, cellular and clinical aspects of MSMD since the last comprehensive review published in 2014. Highlights include the discoveries of (1) a new genetic etiology, autosomal recessive signal peptide peptidase-like 2 A deficiency, (2) TYK2-deficient patients with a clinical phenotype of MSMD, (3) an allelic form of partial recessive IFN-cR2 deficiency, and (4) two forms of syndromic MSMD: RORc/RORcT and JAK1 deficiencies. These recent findings illustrate how genetic and immunological studies of MSMD can shed a unique light onto the mechanisms of protective immunity to mycobacteria in humans.

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Section: Introductionsupporting

confidence: 61%

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

et al. 2018

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“…A few hundred patients with IL12Rβ1 deficiency have been reported in the literature ( 3 ). To our knowledge, till now only three patients with IL12Rβ1-deficiency and clinically significant autoimmune manifestations, including SLE-like disease and autoimmune hemolytic anemia, have been presented ( 8 , 9 ). This is the first association of a primary immunodeficiency with autoimmunity in the form of SS and a very rare case of manifested autoimmunity in case of IL12Rβ1-deficiency.…”

Section: Discussionmentioning

confidence: 99%

First Association of Interleukin 12 Receptor Beta 1 Deficiency with Sjögren’s Syndrome

et al. 2017

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IntroductionInterleukin 12 receptor beta 1 (IL12Rβ1) deficiency is a primary immunodeficiency resulting mainly in susceptibility to opportunistic infection by non-tuberculous, environmental mycobacteria and severe infection caused by Salmonella spp. Till now, less than 300 patients with IL12Rβ1 deficiency have been reported. Among them, only three have been described to develop autoimmunity.Case presentationWe present the case of a 50-year-old male with IL12Rβ1 deficiency due to compound heterozygosity [c. 1623_1624delGCinsTT (pGln542Stop) and c.1791 + 2T > C (donor splice site)], who—18 months after diagnosis of disseminated BCGitis—presented with recurrent fever and sicca syndrome. No indication of an infectious origin of these symptoms could be found at that point. The diagnosis of a Sjögren’s syndrome (SS) was made on the basis of fulfilled American-European consensus classification criteria, including a positive minor salivary gland biopsy.ConclusionApart from persistent antigenic stimulation, which may drive autoimmune inflammation in primary immunodeficiency, evidence on the involvement of interleukin 12 in pathogenesis of SS suggests that the same immunological mechanism may underlie both defense against infection and the maintenance of tolerance. To our knowledge, this is the first report of a case of autoimmunity in the form of SS in a patient with a primary immunodeficiency and one of the rare cases of IL12Rβ1 deficiency with manifested autoimmunity.

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“…9 Patients with IL-12Rβ1 deficiency are susceptible to infections caused by weakly virulent mycobacteria such as the BCG vaccine and EM. 6 Many studies report that the most common infection found in patients with IL-12Rβ1 deficiency continues to be M. bovis BCG disseminated disease due to 85% vaccination coverage worldwide. On the other hand, it is well-recognized that IL-12Rβ1 deficiency-related M. tuberculosis diseases have only been seen in a small number of patients.…”

Section: Volume 61 • Number 2 Clinical Features Of Il-12rβ1 Deficiencymentioning

confidence: 99%

“…Defects in any pathway of the IL-12/IFNγ axis play a role in the pathogenesis of the disease. 5,6 The aim of this study was to summarize the clinical manifestations and genetic analysis of 10 patients with IL-12Rβ1 deficiency in a single tertiary centre from Turkey.…”

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confidence: 99%

Clinical findings and genetic analysis of the patients with IL-12Rβ1 deficiency from southeast Turkey

Doğruel¹,

Gündeşli̇oğlu²,

Yılmaz³

et al. 2019

Turk J Pediatr

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IL-12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to poorly pathogenic mycobacteria, salmonella and candida species. We aimed to analyze the clinical manifestations, immunological and genetic features of IL-12Rβ1 deficiency in 10 Turkish patients from a single center. We retrospectively studied the clinical manifestations and genetic analysis of the IL-12Rβ1 deficiency patients from 2008 to 2016. Ten patients were diagnosed and followed for eight years. The mean age at onset and diagnosis were 24.1±42.5 (med:10.5) and 52.3±6.83 (med:20) months, respectively. Parental consanguinity rate was 81.8%. All patients were BCG vaccinated. Abscess and axillary lymphadenopathy in the vaccinated area was the most common initial presentation following the BCG vaccination, six patients had recurring oral candidiasis. Active infections were treated appropriately, in addition to prophylactic therapy with IFNɣ. We identified 6 different mutations in the IL12RB1 gene in 10 patients including 5 splice-site mutations, 3 missense, 1 frameshift, 1 premature stop codon. One of these mutations was novel. The most common mutation was IVS8+1G>A(c.783+1G>A) followed by p.R175W(c.523C>T). This study emphasizes that patients presented with abscess and axillary lymphadenopathy associated with BCG vaccination should be evaluated for IL-12Rβ1 deficiency.

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Infectious diseases, autoimmunity and midline defect in a patient with a novel bi-allelic mutation in IL12RB1 gene

Cited by 16 publications

References 11 publications

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

First Association of Interleukin 12 Receptor Beta 1 Deficiency with Sjögren’s Syndrome

Clinical findings and genetic analysis of the patients with IL-12Rβ1 deficiency from southeast Turkey

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