TY - JOUR
T1 - NLRP3 inflammasome is associated with the response to IFN-b in patients with multiple sclerosis
AU - Malhotra, Sunny
AU - Rio, Jordi
AU - Urcelay, Elena
AU - Nurtdinov, Ramil
AU - Bustamante, Marta F.
AU - Fernandez, Oscar
AU - Oliver, Begona
AU - Zettl, Uwe
AU - Brassat, David
AU - Killestein, Joep
AU - Lechner-Scott, Jeannette
AU - Drulovic, Jelena
AU - Chan, Andrew
AU - Martinelli-Boneschi, Filippo
AU - Garcia-Merino, Antonio
AU - Montalban, Xavier
AU - Comabella, Manuel
N1 - Funding Information:
The authors thank the ‘Red Española de Esclerosis Múltiple (REEM)’ sponsored by the FEDER-FIS and the ‘Ajuts per donar Suport als Grups de Recerca de Catalunya, sponsored by the ‘Agència de Gestió d’Ajuts Universitaris i de Recerca’ (AGAUR), Generalitat de Catalunya, Spain.
Publisher Copyright:
© 2015 The Author.
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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.
KW - Association study
KW - Biomarkers
KW - Imaging
KW - Multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=84927957370&partnerID=8YFLogxK
U2 - 10.1093/brain/awu388
DO - 10.1093/brain/awu388
M3 - Article
C2 - 25586466
AN - SCOPUS:84927957370
SN - 0006-8950
VL - 138
SP - 644
EP - 652
JO - Brain
JF - Brain
IS - 3
ER -