Polymorphism in BACH2 gene is a marker of polyglandular autoimmunity

Fichna, Marta; Żurawek, Magdalena; Słomiński, Bartosz; Sumińska, Marta; Czarnywojtek, Agata; Rozwadowska, Natalia; Fichna, Piotr; Myśliwiec, Małgorzata; Ruchała, Marek

doi:10.1007/s12020-021-02743-9

Cited by 12 publications

(9 citation statements)

References 56 publications

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“…Most recently, evidence by Fichna et al. appears to show that BTB domain and CNC homolog 2 ( BACH2 ) gene polymorphism, implicated in lymphocyte differentiation and function, may also promote multitarget autoimmunity ( 47 ). Genetic screening is growing popular to identify patients at risk of autoimmune disorders, though this remains too expensive to be included in routine clinical management and is not readily available.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune polyglandular syndrome type 4: experience from a single reference center

Gatta,

Anelli,

Cimino

et al. 2023

Front. Endocrinol.

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PurposeTo characterize patients with APS type 4 among those affected by APS diagnosed and monitored at our local Reference Center for Autoimmune Polyglandular Syndromes.MethodsMonocentric observational retrospective study enrolling patients affected by APS diagnosed and monitored in a Reference Center. Clinical records were retrieved and analyzed.Results111 subjects (51 males) were affected by APS type 4, mean age at the onset was 23.1 ± 15.1 years. In 15 patients the diagnosis of APS was performed during the first clinical evaluation, in the other 96 after a latency of 11 years (range 1-46). The most frequent diseases were type I diabetes mellitus and celiac disease, equally distributed among sexes.ConclusionsThe prevalence of APS type 4 is 9:100,000 people. Type I diabetes mellitus was the leading indicator of APS type 4 in 78% subjects and in 9% permitted the diagnosis occurring as second manifestation of the syndrome. Our data, showing that 50% of patients developed APS type 4 within the first ten years, don’t suggest any particular follow-up time and, more importantly, don’t specify any particular disease. It is important to emphasize that 5% of women developed premature ovarian failure.

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Section: Discussionmentioning

confidence: 99%

Autoimmune polyglandular syndrome type 4: experience from a single reference center

Gatta,

Anelli,

Cimino

et al. 2023

Front. Endocrinol.

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“…Many of the identified differentially methylated genes have important roles in T-cell and immune function. As an example, BACH2 is a transcription factor that regulates lymphocyte development [ 86 ], and polymorphisms in BACH2 have been associated with some autoimmune conditions [ 87 ]. It has been reported that BACH2 participates in oxidative stress-mediated apoptosis and is involved in innate immunity and adaptive immune responses [ 88 ].…”

Section: Discussionmentioning

confidence: 99%

Blood levels of T-Cell Receptor Excision Circles (TRECs) provide an index of exposure to traumatic stress in mice and humans

et al. 2022

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Exposure to stress triggers biological changes throughout the body. Accumulating evidence indicates that alterations in immune system function are associated with the development of stress-associated illnesses such as major depressive disorder and post-traumatic stress disorder, increasing interest in identifying immune markers that provide insight into mental health. Recombination events during T-cell receptor rearrangement and T-cell maturation in the thymus produce circular DNA fragments called T-cell receptor excision circles (TRECs) that can be utilized as indicators of thymic function and numbers of newly emigrating T-cells. Given data suggesting that stress affects thymus function, we examined whether blood levels of TRECs might serve as a quantitative peripheral index of cumulative stress exposure and its physiological correlates. We hypothesized that chronic stress exposure would compromise thymus function and produce corresponding decreases in levels of TRECs. In male mice, exposure to chronic social defeat stress (CSDS) produced thymic involution, adrenal hypertrophy, and decreased levels of TRECs in blood. Extending these studies to humans revealed robust inverse correlations between levels of circulating TRECs and childhood emotional and physical abuse. Cell-type specific analyses also revealed associations between TREC levels and blood cell composition, as well as cell-type specific methylation changes in CD4T + and CD8T + cells. Additionally, TREC levels correlated with epigenetic age acceleration, a common biomarker of stress exposure. Our findings demonstrate alignment between findings in mice and humans and suggest that blood-borne TRECs are a translationally-relevant biomarker that correlates with, and provides insight into, the cumulative physiological and immune-related impacts of stress exposure in mammals.

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“…Lymphocyte maturation defects and upper respiratory chest infections have been reported in patients with BACH2 heterozygous mutations (Afzali et al 2017). Recent human genetic studies indicated a genetic polymorphism within the BACH2 gene locus and its association with autoimmune conditions such as autoimmune thyroid disease, Addison's disease, systemic lupus erythematosus among others and diabetes type 1 (Fichna et al 2021). In addition, BACH2 had a signi cant effect in human diabetes type 2 islets by restoring a nondiabetic phenotype (Son et al 2021) and in a gene expression pro ling study of patients with myocardial infarction (Qiu and Liu 2019).…”

Section: Discussionmentioning

confidence: 99%

Knockout mouse models as a resource for rare diseases studies

Silva-Buttkus

Spielmann

Klein-Rodewald

et al. 2022

Preprint

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Rare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestation and low prevalence. There is a lack of specific treatments and only a few hundred of the approximately 7.000 RDs have an approved regime. Rapid technological development in genome sequencing enables the mass identification of potential candidates that in their mutated form could trigger diseases but are often not confirmed to be causal. Knockout (KO) mouse models are essential to understand the causality of genes by allowing highly standardized research into the pathogenesis of diseases. The German Mouse Clinic (GMC) is one of the pioneers in mouse research and successfully uses (preclinical) data obtained from single-gene KO mutants for research into monogenic RDs. As part of the International Mouse Phenotyping Consortium and INFRAFRONTIER, the pan-European consortium for modelling human diseases, the GMC expands these preclinical data towards global collaborative approaches with researchers, clinicians and patient groups. Here, we highlight proprietary genes like proof-of-concept RD targets (Nacc1, Bach2, Klotho alpha). We focus on recognized RD genes with no pre-existing KO mouse models (Kansl1l, Acsf3, Pcdhgb2, Rabgap1, Cox7a2) and novel phenotypes capable of optimising clinical diagnostic (Rabgap1, Pcdhgb2). In addition, we present yet unknown RD genes with intriguing phenotypic data (Zdhhc5, Wsb2) not presently associated with known human RDs that may have a justified case to suggest causal genes underlying so far undiagnosed diseases. This report provides comprehensive evidence for genes that when deleted cause differences in the KO mouse across multiple organs, providing a huge translational potential for further understanding monogenic RDs and their clinical spectrum. Genetic KO studies in mice are valuable to explore further the underlying physiological mechanisms and its overall therapeutic potential.

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Polymorphism in BACH2 gene is a marker of polyglandular autoimmunity

Cited by 12 publications

References 56 publications

Autoimmune polyglandular syndrome type 4: experience from a single reference center

Autoimmune polyglandular syndrome type 4: experience from a single reference center

Blood levels of T-Cell Receptor Excision Circles (TRECs) provide an index of exposure to traumatic stress in mice and humans

Knockout mouse models as a resource for rare diseases studies

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