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Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behcet's syndrome patients


Yüksel, Şahru; Eren, Elif; Hatemi, Gülen; et al (2014). Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behcet's syndrome patients. International Immunology, 26(2):71-81.

Abstract

Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of mutation(s), we performed single-strand conformation polymorphism analyses and/or sequencing of all the coding regions and intron-exon boundaries of NLRP3/cryopyrin and ASC (apoptosis-associated speck-like protein containing CARD) genes from Turkish BS patients and healthy controls. At the same time, we determined pro-inflammatory cytokine secretion profiles of peripheral blood cells in response to LPS treatment using ELISA. BS patients with vascular involvement showed significantly increased levels of TNF-α release at 2-, 4- and 8-h post-treatment and significantly increased IL-1β levels were detected at 2h (P = 0.005) and 4h (P = 0.025) (n = 10). We identified four mutations in the NLRP3/cryopyrin gene, V200M (n = 3/104) and T195M (n = 1/104), in BS patients but none in control samples. No mutations were detected in the ASC gene. The effect of these NLRP3/cryopyrin mutants on ASC speck assembly and IL-1β secretion was tested and the V200M mutant was shown to induce IL-1β secretion. Thus, it is likely that certain mutations in NLRP3/cryopyrin in combination with yet unknown other factors may contribute to the pro-inflammatory cytokine profiles in BS patients.

Abstract

Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of mutation(s), we performed single-strand conformation polymorphism analyses and/or sequencing of all the coding regions and intron-exon boundaries of NLRP3/cryopyrin and ASC (apoptosis-associated speck-like protein containing CARD) genes from Turkish BS patients and healthy controls. At the same time, we determined pro-inflammatory cytokine secretion profiles of peripheral blood cells in response to LPS treatment using ELISA. BS patients with vascular involvement showed significantly increased levels of TNF-α release at 2-, 4- and 8-h post-treatment and significantly increased IL-1β levels were detected at 2h (P = 0.005) and 4h (P = 0.025) (n = 10). We identified four mutations in the NLRP3/cryopyrin gene, V200M (n = 3/104) and T195M (n = 1/104), in BS patients but none in control samples. No mutations were detected in the ASC gene. The effect of these NLRP3/cryopyrin mutants on ASC speck assembly and IL-1β secretion was tested and the V200M mutant was shown to induce IL-1β secretion. Thus, it is likely that certain mutations in NLRP3/cryopyrin in combination with yet unknown other factors may contribute to the pro-inflammatory cytokine profiles in BS patients.

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9 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2014
Deposited On:24 Mar 2014 13:46
Last Modified:05 Apr 2016 17:44
Publisher:Oxford University Press
ISSN:0953-8178
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/intimm/dxt046
PubMed ID:24135410

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