Different molecular behavior of CD40 mutants causing hyper-IgM syndrome

Lanzi, Gaetana; Ferrari, Simona; Vihinen, Mauno; Caraffi, Stefano Giuseppe; Kütükçüler, Necil; Schiaffonati, Luisa; Plebani, Alessandro; Notarangelo, Luigi D.; Fra, Annamaria; Giliani, Silvia

doi:10.1182/blood-2010-03-274241

Cited by 30 publications

(16 citation statements)

References 38 publications

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“…CD40 is constitutively expressed on B cells, and its interaction with CD40L expressed on CD4+ T cell is essential for immunoglobulin class-switch and peripheral B cell tolerance. Genetic defects in CD40L led to a disorder characterized by elevated serum IgM, which recaptures one of major serology features of PBC [160]. Early reports indicate that hepatic CD40L mRNA was significantly increased in PBC compared with healthy controls and several other liver diseases [161].…”

Section: Dna Methylationmentioning

confidence: 98%

Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity

Xie

Lian

2015

Clinic Rev Allerg Immunol

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Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that develops based upon the interaction of genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified dozens of predisposing variants including HLA, IL12A, and CTLA4 but have been disappointed in identifying a "smoking gun." These discoveries highlight the importance of the genetic background involved in immunological dysregulation. Although concordance rate of PBC in monozygotic (MZ) twins is among the highest reported in autoimmune disorders, incomplete disease concordance in twins associated with differentially expressed genes has been demonstrated. However, little is understood about how environmental aspects contribute to the disease and why middle-aged women are more susceptible. As a result, epigenetic factors, which convert signals indicating environmental changes into dynamic and heritable alterations of transcriptional potential, are getting increased attention by researchers in both basic and clinical studies. Among epigenetic mechanisms, the instability and skewed gene expression in the X chromosome may account for the female preponderance in PBC. In addition, transcriptional regulation of histone modification and DNA methylation underscores potential involvement in disease pathogenesis. High-throughput techniques are being used to identify epigenetic regulators. In this review, we attempt to outline recent progress regarding epigenetics in PBC and other autoimmune diseases.

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Section: Dna Methylationmentioning

confidence: 98%

Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity

Xie

Lian

2015

Clinic Rev Allerg Immunol

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“…Missense mutations or small in-frame deletions in 4 of the reported patients with CD40 deficiency were able to generate mutated proteins. However, these were retained in the endoplasmic reticulum and thus not expressed in the cell membrane (Lanzi et al 2010). …”

Section: Discussionmentioning

confidence: 99%

“…These factors function as adaptor molecules to recruit different kinases (e.g., mitogen-activated protein kinases or MAPKs, extracellular signal-regulated kinase or ERK, phospholipase Cγ2, syk, and phosphatidylinositol 3) resulting in activation of the transcription factors: activator protein-1 (AP-1) and NFκB (Lougaris et al 2005;Notarangelo et al 2006;Lanzi et al 2010). Signaling mediated by CD40 might also involve pathways independent of TRAFs, such as activation of Janusassociated kinases (JAKs), particularly JAK3, and also signal transducers and activators of transcription (STATs), mainly STAT6 and STAT3 (Lougaris et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Cd40 Deficiency: A Unique Adult Patient With Hyper Immunoglobulin M Syndrome and Normal Expression of Cd40

Murguía-Favela¹,

Sharfe

Karanxha

et al. 2017

LymphoSign Journal

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Background: CD40 deficiency is an autosomal recessive, combined primary immunodeficiency characterized by defects of immunoglobulin class switch recombination and somatic hypermutation. It is part of an expanding group of diseases collectively known as hyper immunoglobulin M syndromes. Clinical manifestations of the disease usually begin early in life with recurrent sinopulmonary bacterial infections and susceptibility to opportunistic organisms. Only 16 patients from 12 unrelated families have been reported to date, all with lack of membrane expression of CD40 molecule.

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“…CD40 is also expressed on follicular dendritic cells, thymic epithelial cells, and monocytes. Patients with HIGM type 3 are clinically undistinguishable from subjects carrying genetic defects in CD40L [22]. Mutations in both CD40L and CD40 result in immunoglobulin class-switch recombination deficiency generally associated with reduced somatic hypermutation generation.…”

Section: Introductionmentioning

confidence: 99%

Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature

et al. 2011

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Different molecular behavior of CD40 mutants causing hyper-IgM syndrome

Cited by 30 publications

References 38 publications

Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity

Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity

Cd40 Deficiency: A Unique Adult Patient With Hyper Immunoglobulin M Syndrome and Normal Expression of Cd40

Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature

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