NLRP3 inflammasome is associated with the response to IFN-β in patients with multiple sclerosis. (12th January 2015)

• Record Type: Journal Article
• Authors: Malhotra, Sunny; Río, Jordi; Urcelay, Elena; Nurtdinov, Ramil; Bustamante, Marta F; Fernández, Oscar; Oliver, Begoña; Zettl, Uwe; Brassat, David; Killestein, Joep; Lechner-Scott, Jeannette; Drulovic, Jelena; Chan, Andrew; Martinelli-Boneschi, Filippo; García-Merino, Antonio; Montalban, Xavier; Comabella, Manuel
• Is Part Of: Brain. Volume 138:Part 3(2015:Mar.)
• Page Start: 644
• Page End: 652
• Publication Date: 2015-01-12
• Subjects: biomarkers -- association study -- multiple sclerosis -- imaging; Neurology -- Periodicals; 616.8005
• DOI: 10.1093/brain/awu388
• Languages: English
• ISSNs: 0006-8950

Abstract

Abstract : Evidence exists that interferon-beta therapy can modulate inflammasome activity in multiple sclerosis. However, the role of inflammasomes in shaping the interferon-beta response is unclear. Malhotra et al. report that expression of the NLRP3 inflammasome and the related cytokine IL1B in blood cells discriminates between interferon-beta responders and non-responders. Abstract : Evidence exists for a potential modulation of inflammasome activity by interferon beta. Here, we investigated the roles of inflammasomes [absent in melanoma 2 ( AIM2 ); NLR family, CARD domain containing 4 ( NLRC4 ); NLR family, pyrin domain containing 1 and 3 ( NLRP1 and NLRP3 )] and related cytokines ( IL1B, IL10, IL18 ) in the response to interferon beta in patients with relapsing-remitting multiple sclerosis. Ninety-seven patients treated with interferon beta were classified into responders and non-responders according to clinical criteria after 24 months and clinical-radiological criteria after 12 months of treatment. Messenger RNA expression levels of inflammasomes and cytokines were determined by real-time polymerase chain reaction in peripheral blood mononuclear cells collected before treatment with interferon beta. In a subgroup of patients, NLRP3 and IL1B expression was also determined after 3 months ( n = 32) and 12 months ( n = 20) of interferon beta treatment. A polymorphism located in the NLRP3 gene, rs35829419, was genotyped in 789 multiple sclerosis patients treated with interferon beta. Baseline mRNA expression levels for NLRP3 and IL1B were increased in peripheral blood mononuclear cells from non-responders compared to responders classified according to clinical criteria after 24 months ( P = 0.02 and P = 0.001, respectively). No significant differences were observed for other inflammasomes and related cytokines. Differences in NLRP3 and IL1B expression remained significant following a clinical-radiological classification after 12 months ( P = 0.007 and P = 0.02, respectively). After treatment with interferon beta, NLRP3 and IL1B expression was increased in responders but unchanged in non-responders. A trend for association was observed between rs35829419 and interferon beta response (pM-H = 0.08). These results point to a role of the NLRP3 inflammasome and its related cytokine IL1B in the response to interferon beta in patients with relapsing-remitting multiple sclerosis.