RT Journal Article
T1 NLRP3 inflammasome as prognostic factor and therapeutic target in primary progressive multiple sclerosis patients
A1 Malhotra, Sunny
A1 Costa, Carme
A1 Eixarch, Herena
A1 Keller, Christian W
A1 Lukas Amman, Lukas
A1 Martínez-Banaclocha, Helios
A1 Midaglia, Luciana
A1 Sarró, Eduard
A1 Isabel Machín-Díaz, Isabel
A1 M Villar, Luisa
A1 Triviño, Juan Carlos
A1 Oliver-Martos, Begoña
A1 Navarro Parladé, Laura
A1 Calvo-Barreiro, Laura
A1 Matesanz, Fuencisla
A1 Vandenbroeck, Koen
A1 Urcelay, Elena
A1 María-Luisa Martínez-Ginés, María-Luisa
A1 Tejeda-Velarde, Amalia
A1 Fissolo, Nicolás
A1 Castilló, Joaquín
A1 Sanchez, Alex
A1 Robertson, Avril A B
A1 Clemente, Diego
A1 Prinz, Marco
A1 Pelegrin, Pablo
A1 Lünemann, Jan D
A1 Espejo, Carmen
A1 Montalban, Xavier
A1 Comabella, Manuel
K1 Esclerosis múltiple
AB Primary progressive multiple sclerosis is a poorly understood disease entity with no specific prognostic biomarkers and scarce therapeutic options. We aimed to identify disease activity biomarkers in multiple sclerosis by performing an RNA sequencing approach in peripheral blood mononuclear cells from a discovery cohort of 44 untreated patients with multiple sclerosis belonging to different clinical forms and activity phases of the disease, and 12 healthy control subjects. A validation cohort of 58 patients with multiple sclerosis and 26 healthy control subjects was included in the study to replicate the RNA sequencing findings. The RNA sequencing revealed an interleukin 1 beta (IL1B) signature in patients with primary progressive multiple sclerosis. Subsequent immunophenotyping pointed to blood monocytes as responsible for the IL1B signature observed in this group of patients. Functional experiments at baseline measuring apoptosis-associated speck-like protein containing a CARD (ASC) speck formation showed that the NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome was overactive in monocytes from patients with primary progressive multiple sclerosis, and canonical NLRP3 inflammasome activation with a combination of ATP plus lipopolysaccharide was associated with increased IL1B production in this group of patients.
PB Oxford Academic
YR 2020
FD 2020
LK https://hdl.handle.net/10630/33925
UL https://hdl.handle.net/10630/33925
LA eng
NO Malhotra S, Costa C, Eixarch H, Keller CW, Amman L, Martínez-Banaclocha H, Midaglia L, Sarró E, Machín-Díaz I, Villar LM, Triviño JC, Oliver-Martos B, Parladé LN, Calvo-Barreiro L, Matesanz F, Vandenbroeck K, Urcelay E, Martínez-Ginés ML, Tejeda-Velarde A, Fissolo N, Castilló J, Sanchez A, Robertson AAB, Clemente D, Prinz M, Pelegrin P, Lünemann JD, Espejo C, Montalban X, Comabella M. NLRP3 inflammasome as prognostic factor and therapeutic target in primary progressive multiple sclerosis patients. Brain. 2020 May 1;143(5):1414-1430. doi: 10.1093/brain/awaa084. PMID: 32282893.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026