Production of IL-1beta and IL-1Ra as risk factors for susceptibility and progression of relapse-onset multiple sclerosis.
Interleukin-1beta (IL-1beta) is present in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1Ra) moderates the induction of experimental autoimmune encephalomyelitis (EAE). Here, we show that families that are characterized by high IL-1beta over IL-1Ra production ratio are at 2.2-fold (95% CI, 1.0-4.8; p=0.05) increased risk to have a patient relative with relapse-onset MS than families with a low ratio. It is also related to the reduction of volumetric magnetization transfer ratio (MTR) histogram height, a measure of parenchymal integrity (p=0.04). Those families who combine a high IL-1beta over IL-1Ra ratio with a high tumor necrosis factor (TNF) over IL-10 production ratio have a 6.2-fold (95% CI, 1.8-21; p=0.002) increased risk. Innate production of IL-1beta and IL-1Ra is not related to the outcome of primary progressive MS. Taq1 polymorphism in the IL-1beta gene and the variable number of tandem repeats (VNTR) polymorphism of 86-base pairs within the IL-1Ra gene cannot explain these findings.
de Jong
Brigit A
BA
Department of Clinical Epidemiology, LUMC, Leiden, The Netherlands.
Huizinga
Tom W J
TW
Bollen
Eduard L E M
EL
Uitdehaag
Bernard M J
BM
Bosma
Gerlof P Th
GP
van Buchem
Mark A
MA
Remarque
Edmond J
EJ
Burgmans
Alexandra C S
AC
Kalkers
Nynke F
NF
Polman
Chris H
CH
Westendorp
Rudi G J
RG
D000328:Adult; D000368:Aged; D018450:Disease Progression; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics*; D020080:Tandem Repeat Sequences
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins