NLRP3 inflammasome is associated with the response to IFN-β in patients with multiple sclerosis

被引：89

作者：

Malhotra, Sunny ^{[1
]}

Rio, Jordi ^{[1
]}

Urcelay, Elena ^{[2
]}

Nurtdinov, Ramil ^{[1
]}

Bustamante, Marta F. ^{[1
]}

Fernandez, Oscar ^{[3
]}

Oliver, Begona ^{[3
]}

Zettl, Uwe ^{[4
]}

Brassat, David ^{[5
,6
]}

Killestein, Joep ^{[7
]}

Lechner-Scott, Jeannette ^{[8
,9
]}

Drulovic, Jelena ^{[10
]}

Chan, Andrew ^{[11
]}

Martinelli-Boneschi, Filippo ^{[12
,13
]}

Garcia-Merino, Antonio ^{[14
]}

Montalban, Xavier ^{[1
]}

Comabella, Manuel ^{[1
]}

机构：

[1] Univ Autonoma Barcelona, Inst Receca Vall dHebron VHIR, Ctr Esclerosi Multiple Catalunya Cemcat, Serv Neurol Neuroimmunol,Hosp Univ Vall dHebron, E-08193 Barcelona, Spain

[2] Hosp Clin San Carlos, Serv Neurol, Madrid, Spain

[3] Univ Malaga, Unidad Gest Clin Neurociencias, Inst Biomed Malaga IBIMA, Hosp Univ Reg Malaga, E-29071 Malaga, Spain

[4] Univ Rostock, Dept Neurol, D-18055 Rostock, Germany

[5] Univ Toulouse 3, Pole Neurosci, Hop Purpan, F-31062 Toulouse, France

[6] Univ Toulouse 3, INSERM, U1043, Hop Purpan, F-31062 Toulouse, France

[7] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands

[8] John Hunter Hosp, Dept Neurol, Newcastle, NSW, Australia

[9] Univ Newcastle, Hunter Med Res Inst, Callaghan, NSW 2308, Australia

[10] Univ Belgrade, Neurol Clin, Clin Ctr Serbia, Fac Med, Belgrade 11001, Serbia

[11] Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, Bochum, Germany

[12] Ist Sci San Raffaele, Lab Genet Neurol Complex Disorders, I-20132 Milan, Italy

[13] Ist Sci San Raffaele, Dept Neurol, Inst Expt Neurol INSPE, Div Neurosci, I-20132 Milan, Italy

[14] Hosp Univ Puerta Hierro, Madrid, Spain

来源：

BRAIN | 2015年 / 138卷

关键词：

biomarkers; association study; multiple sclerosis; imaging; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INTERFERON-BETA; ACTIVATION; EXPRESSION; GENE; DISEASE; CNS;

D O I：

10.1093/brain/awu388

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 (p(M-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.

引用

页码：644 / 652

页数：9

共 20 条

[1] Activated Human CD4+CD45RO+Memory T-Cells Indirectly Inhibit NLRP3 Inflammasome Activation through Downregulation of P2X7R Signalling [J].