Association between the nod2-isoform val955ile and myelin basic protein-induced t cell responses in patients with multiple sclerosis

Chris Juul Hedegaard, C. Enevold, K. Bendtzen, C. H. Nielsen

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Abstract

Objective: Following stimulation of the nucleotide oligomerization domain 2 (NOD2) receptor with muramyldipeptide (MDP), monocytes secrete interleukin (IL)-
23 and IL-1, which, in turn, promote IL-17 secretion in memory T cells. IL-17 plays a deleterious role in multiple sclerosis (MS). Mutations in the NOD2 gene
(CARD15) confer susceptibility to certain chronic inflammatory disorders. Three polymorphisms in CARD15, resulting in Pro268Ser, Arg703Cys and Val955Ile substitutions, are all more frequent than 1% in Caucasians, but it has not been investigated whether they are associated with MS.
Methods: Genotyping of the three polymorphisms was carried out on bead-based SNP-analysis using the Luminex platform on 24 patients with MS. CFSE-labelled mononuclear cell (MNC) cultures were stimulated with myelin basic protein (MBP). The consequent production of IL-17 was measured by Luminex techology, and CD4+ T cell proliferation was measured flow cytometrically as dilution of the cellular CFSE content.
Results: None of the patients were homozygous for the Ile955 isoform, while five were heterozygous. MBP induced CD4+ T cell proliferation MNC cultures from
all of the heterozygous patients versus only four of the 19 patients with wild type (P X 0.003). Moreover, the 955Ile allele was associated with MBP-induced production of IL-17 (P X 0.03), which was displayed by eight of the nine patients with CD4+ T cell proliferation.
Conclusion: We hypothesize that the Ile955 isoform of NOD2 plays a role in determining MBP-elicited CD4+ T cell proliferation and IL-17 production in MS
patients.
Original languageEnglish
JournalEuropean Journal of Immunology
Volume39
Issue numberSuppl 1
Pages (from-to)489
Number of pages1
ISSN0014-2980
Publication statusPublished - 2009
Externally publishedYes
Event2nd European Congress of Immunology - Berlin, Germany
Duration: 13 Sep 200916 Sep 2009
Conference number: 2

Conference

Conference2nd European Congress of Immunology
Number2
CountryGermany
CityBerlin
Period13/09/200916/09/2009

Bibliographical note

PC18/17

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