DOI: 10.1101/491837Dec 10, 2018Paper

Genetically distinct clinical subsets, and associations with asthma and eosinophil abundance, within Eosinophilic Granulomatosis with Polyangiitis

BioRxiv : the Preprint Server for Biology
Paul A LyonsKenneth G C Smith

Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA: formerly Churg-Strauss syndrome) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasm antibodies (ANCA) specific for myeloperoxidase (MPO). We performed a genome-wide association study (GWAS) of EGPA, testing 7.5 million genetic variants in 684 cases and 6,838 controls. Case-control analyses were performed for EGPA as a whole, and stratified by ANCA. To increase power, we used a conditional false discovery rate method to leverage findings from GWASs of related phenotypes. In total, 11 variants were associated with EGPA, two specifically with ANCA-negative EGPA, and one (HLA-DQ) with MPO+ANCA EGPA. Many variants were associated with asthma, eosinophilic and immune-mediated diseases and, strikingly, nine were associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia underlies EGPA susceptibility. We demonstrate that EGPA comprises two genetically and clinically distinct syndromes, with ANCA-negative EGPA genetically more similar to asthma. MPO+ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an MHC association with MP...Continue Reading

Related Concepts

Asthma
Autoimmune Diseases
Churg-Strauss Syndrome
Disease Susceptibility
Eosinophilia
Eosinophil
Gram-Negative Bacteria
HLA-DQ Antigens
Peroxidase
Granulomatosis

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Asthma

This feed focuses in Asthma in which your airways narrow and swell. This can make breathing difficult and trigger coughing, wheezing and shortness of breath.

Asthma (Preprints)

Asthma is a condition in which your airways narrow and swell. This can make breathing difficult and trigger coughing, wheezing and shortness of breath. Discover the latest preprints here.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

American Thoracic Society: Clinical Problems

This feed has been developed in conjunction with the American Thoracic Society for the benefit of its Clinical Problems Assembly. It highlights new and impactful papers on clinical therapeutics, diagnoses, and practices pertaining to respiratory disease.

Related Papers

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Matthieu GrohLoïc Guillevin
The New England Journal of Medicine
Paul A LyonsKenneth G C Smith
Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete
N KlossowskiS Meller
© 2021 Meta ULC. All rights reserved