A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn's Disease

Laffin, Michael; Fedorak, Richard N.; Wine, Eytan; Dicken, Bryan; Madsen, Karen

doi:10.1016/j.jamcollsurg.2018.01.052

Cited by 10 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Laffin et al studied a cohort of patients with CD who underwent intestinal resection and identified Bach2 as a susceptibility locus for postoperative recurrence of CD. They hypothesized that a Bach2 mutation can make the patient at increased risk of an inappropriate inflammatory response to microorganisms after intestinal resection [57]. Although variation in Bach2 shows more relevant to CD, Christodoulou et al examined two patients with severe UC and observed they both carried unique, potentially detrimental mutation in Bach2 gene [58].…”

Section: Type 2 Chronic Airwaymentioning

confidence: 99%

The Critical Role of Bach2 in Shaping the Balance between CD4⁺ T Cell Subsets in Immune-Mediated Diseases

Yang

Chen

Zhao

et al. 2019

Mediators of Inflammation

View full text Add to dashboard Cite

The transcription factor Bach2 which is predominantly expressed in B and T lymphocytes represses the expression of genes by forming heterodimers with small Maf and Batf proteins and binding to the corresponding sequence on the DNA. In this way, Bach2 serves as a highly conserved repressor which controls the terminal differentiation and maturation of both B and T lymphocytes. It is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells, and its function in B cell differentiation has been well-described. Furthermore, emerging data show that Bach2 regulates transcriptional activity in T cells at super enhancers or regions of high transcriptional activity, thus stabilizing immunoregulatory capacity and maintaining T cell homeostasis. Bach2 is also critical for the formation and function of CD4+ T cell lineages (Th1, Th2, Th9, Th17, T follicular helper (Tfh), and regulatory T (Treg) cells). Genetic variations within Bach2 locus are associated with numerous immune-mediated diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), chronic pancreatitis (CP), type 2 chronic airway inflammation, inflammatory bowel disease (IBD), and type 1 diabetes. Here, we reveal a critical role of Bach2 in regulating T cell biology and the correlation with these immune-mediated diseases.

show abstract

Section: Type 2 Chronic Airwaymentioning

confidence: 99%

The Critical Role of Bach2 in Shaping the Balance between CD4⁺ T Cell Subsets in Immune-Mediated Diseases

Yang

Chen

Zhao

et al. 2019

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…The FYB gene is related to T cells signaling and plays a role in IL-2A expression, and is known to be associated with some autoimmune regulation [ 48 , 49 ]. Likewise, BACH2 is a critical gene for B cell regulatory activity and T cell function and differentiation and is a known susceptibility locus for CD and UC [ 50 , 51 ]; DOCK8 is known to regulate diverse immune sub-types including lymphocytes and plays a role in immune synapse formation and pathogen proliferation [ 52 ]; and NFKB1 is a known transcription regulator of immune response, apoptosis and cell proliferation and is up-regulated in both UC and CD patients [ 53 ]. On the contrary, although BANK1 is a B cell gene known to be associated with SLE and RA [ 34 , 35 ], only few studies linking specific BANK1 variants to CD has been published [ 54 , 55 ] and it’s role in the pathogenesis of both CD and UC remains understudied.…”

Section: Resultsmentioning

confidence: 99%

multi-GPA-Tree: Statistical approach for pleiotropy informed and functional annotation tree guided prioritization of GWAS results

Khatiwada,

Yilmaz,

Wolf

et al. 2023

PLoS Comput Biol

View full text Add to dashboard Cite

Genome-wide association studies (GWAS) have successfully identified over two hundred thousand genotype-trait associations. Yet some challenges remain. First, complex traits are often associated with many single nucleotide polymorphisms (SNPs), most with small or moderate effect sizes, making them difficult to detect. Second, many complex traits share a common genetic basis due to ‘pleiotropy’ and and though few methods consider it, leveraging pleiotropy can improve statistical power to detect genotype-trait associations with weaker effect sizes. Third, currently available statistical methods are limited in explaining the functional mechanisms through which genetic variants are associated with specific or multiple traits. We propose multi-GPA-Tree to address these challenges. The multi-GPA-Tree approach can identify risk SNPs associated with single as well as multiple traits while also identifying the combinations of functional annotations that can explain the mechanisms through which risk-associated SNPs are linked with the traits. First, we implemented simulation studies to evaluate the proposed multi-GPA-Tree method and compared its performance with existing statistical approaches. The results indicate that multi-GPA-Tree outperforms existing statistical approaches in detecting risk-associated SNPs for multiple traits. Second, we applied multi-GPA-Tree to a systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and to a Crohn’s disease (CD) and ulcertive colitis (UC) GWAS, and functional annotation data including GenoSkyline and GenoSkylinePlus. Our results demonstrate that multi-GPA-Tree can be a powerful tool that improves association mapping while facilitating understanding of the underlying genetic architecture of complex traits and potential mechanisms linking risk-associated SNPs with complex traits.

show abstract

“…Immunological memory was also implicated by genetic studies on BACH2 (a highly conserved transcription factor that is a fundamental element in the maturation of B-lymphocytes and differentiation of T-cells, especially in regulatory T-cells) which independently correlate it to surgical recurrence [49]. The authors speculate the underlying mechanism to be the inability to memorize an appropriate (tolerant) response to luminal antigens.…”

Section: T-cellsmentioning

confidence: 98%

The Role of Inflammation in Crohn’s Disease Recurrence after Surgical Treatment

Sensi

Siragusa

Efrati

et al. 2020

Journal of Immunology Research

View full text Add to dashboard Cite

Introduction. Postoperative recurrence after surgery for Crohn’s disease (CD) is virtually inevitable, and its mechanism is poorly known. Aim. To review the numerous factors involved in CD postoperative recurrence (POR) pathogenesis, focusing on single immune system components as well as the immune system as a whole and highlighting the clinical significance in terms of preventive strategies and future perspectives. Methods. A systematic literature search on CD POR, followed by a review of the main findings. Results. The immune system plays a pivotal role in CD POR, with many different factors involved. Memory T-lymphocytes retained in mesenteric lymph nodes seem to represent the main driving force. New pathophysiology-based preventive strategies in the medical and surgical fields may help reduce POR rates. In particular, surgical strategies have already been developed and are currently under investigation. Conclusions. POR is a complex phenomenon, whose driving mechanisms are gradually being unraveled. New preventive strategies addressing these mechanisms seem promising.

show abstract

A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn's Disease

Cited by 10 publications

References 49 publications

The Critical Role of Bach2 in Shaping the Balance between CD4⁺ T Cell Subsets in Immune-Mediated Diseases

The Critical Role of Bach2 in Shaping the Balance between CD4⁺ T Cell Subsets in Immune-Mediated Diseases

multi-GPA-Tree: Statistical approach for pleiotropy informed and functional annotation tree guided prioritization of GWAS results

The Role of Inflammation in Crohn’s Disease Recurrence after Surgical Treatment

Contact Info

Product

Resources

About

A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn's Disease

Cited by 10 publications

References 49 publications

The Critical Role of Bach2 in Shaping the Balance between CD4+ T Cell Subsets in Immune-Mediated Diseases

The Critical Role of Bach2 in Shaping the Balance between CD4+ T Cell Subsets in Immune-Mediated Diseases

multi-GPA-Tree: Statistical approach for pleiotropy informed and functional annotation tree guided prioritization of GWAS results

The Role of Inflammation in Crohn’s Disease Recurrence after Surgical Treatment

Contact Info

Product

Resources

About

The Critical Role of Bach2 in Shaping the Balance between CD4⁺ T Cell Subsets in Immune-Mediated Diseases

The Critical Role of Bach2 in Shaping the Balance between CD4⁺ T Cell Subsets in Immune-Mediated Diseases