Interleukin 18 receptor 1 expression distinguishes patients with multiple sclerosis.
Definition of dysregulated immune components in multiple sclerosis may help in the identification of new therapeutic targets. Deviation of the interleukin 18 receptor 1 (IL18R1) is of particular interest since the receptor is critical for experimental neuroinflammation. The objective of this study was to determine whether expression of IL18R1 varies between multiple sclerosis patients and controls, and to test genetic association of IL18R1 with multiple sclerosis. We used quantitative real-time PCR to assess mRNA levels of IL18R1 in cerebrospinal fluid and peripheral blood mononuclear cells of 191 patients with multiple sclerosis, 61 patients with clinically isolated syndrome and 168 controls having other neurological disorders. Association was tested in 2153 patients with multiple sclerosis and 1733 controls using 13 tagging single nucleotide polymorphisms within the IL18R1 gene. We found that patients with multiple sclerosis had increased IL18R1 mRNA expression in both cerebrospinal fluid cells (p < 0.05) and peripheral blood mononuclear cells (p < 0.05) compared with controls. Patients with clinically isolated syndrome had elevated levels compared with controls in cerebrospinal fluid cells (p < 0.001) but not in peripheral blood mononuclear cells. The gene was not associated to multiple sclerosis. We conclude that the increased expression of IL18R1 may contribute pathogenically to disease and is therefore a potential therapeutic target. The absence of a genetic association in the IL18R1 gene itself suggests regulation from other parts of the genome, or as part of the inflammatory cascade in multiple sclerosis without a prime genetic cause.
Gillett
Alan
A
Department of Clinical Neuroscience, Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Institutet, Solna, Sweden. alan.gillett@ki.se
Thessen Hedreul
Melanie
M
Khademi
Mohsen
M
Espinosa
Alexander
A
Beyeen
Amennai D
AD
Jagodic
Maja
M
Kockum
Ingrid
I
Harris
Robert A
RA
Olsson
Tomas
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D053727:Interleukin-18 Receptor alpha Subunit / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000097:blood / Q000134:cerebrospinal fluid; D013548:Sweden; D015854:Up-Regulation; D055815:Young Adult
C508572:IL18R1 protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger