CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies.

Related collections

Most cited references 28

Record: found
Abstract: not found
Article: not found

Atypical hemolytic-uremic syndrome.

Marina Noris, Giuseppe Remuzzi (2009)

0 comments Cited 337 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Genetics of Inflammatory Bowel Diseases.

Dermot McGovern, Subra Kugathasan, Judy H Cho (2015)

In this review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and noncoding genetic variation. In the small minority of loci where major association signals correspond to nonsynonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve noncoding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that the expression of most human genes is regulated by noncoding genetic variations. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (ie, odds ratios markedly deviating from 1) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in more severe very early onset cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility through emerging precision medical initiatives. In this article, we discuss the rapidly evolving area of direct-to-consumer genetic testing and the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect to partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD.

0 comments Cited 161 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Complement activation, regulation, and molecular basis for complement-related diseases.

Goran Bajic, Søren E Degn, Steffen Thiel … (2015)

The complement system is an essential element of the innate immune response that becomes activated upon recognition of molecular patterns associated with microorganisms, abnormal host cells, and modified molecules in the extracellular environment. The resulting proteolytic cascade tags the complement activator for elimination and elicits a pro-inflammatory response leading to recruitment and activation of immune cells from both the innate and adaptive branches of the immune system. Through these activities, complement functions in the first line of defense against pathogens but also contributes significantly to the maintenance of homeostasis and prevention of autoimmunity. Activation of complement and the subsequent biological responses occur primarily in the extracellular environment. However, recent studies have demonstrated autocrine signaling by complement activation in intracellular vesicles, while the presence of a cytoplasmic receptor serves to detect complement-opsonized intracellular pathogens. Furthermore, breakthroughs in both functional and structural studies now make it possible to describe many of the intricate molecular mechanisms underlying complement activation and the subsequent downstream events, as well as its cross talk with, for example, signaling pathways, the coagulation system, and adaptive immunity. We present an integrated and updated view of complement based on structural and functional data and describe the new roles attributed to complement. Finally, we discuss how the structural and mechanistic understanding of the complement system rationalizes the genetic defects conferring uncontrolled activation or other undesirable effects of complement.

0 comments Cited 133 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Title: New England Journal of Medicine

Abbreviated Title: N Engl J Med

Publisher: New England Journal of Medicine (NEJM/MMS)

ISSN (Print): 0028-4793

ISSN (Electronic): 1533-4406

Publication date Created: July 06 2017

Publication date (Print): July 06 2017

Volume: 377

Issue: 1

Pages: 52-61

Article

DOI: 10.1056/NEJMoa1615887

PMC ID: 6690356

PubMed ID: 28657829

SO-VID: 42cc8158-fe81-4c73-b894-d7ec070b1e13

History

Data availability:

Comments

Comment on this article

scite_

Cited by 58

See all cited by

- Version 1
- Version 1

CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis

Read this article at

Abstract

Related collections

Journal of Circulating Biomarkers

Most cited references 28

Atypical hemolytic-uremic syndrome.

Genetics of Inflammatory Bowel Diseases.

Complement activation, regulation, and molecular basis for complement-related diseases.

Author and article information

Journal

Article

History

Comments

Comment on this article

Similar content 3,670

Cited by 58