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.
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 language | English |
|---|---|
| Journal | European Journal of Immunology |
| Volume | 39 |
| Issue number | Suppl 1 |
| Pages (from-to) | 489 |
| Number of pages | 1 |
| ISSN | 0014-2980 |
| Publication status | Published - 2009 |
| Externally published | Yes |
| Event | 2nd European Congress of Immunology - Berlin, Germany Duration: 13 Sept 2009 → 16 Sept 2009 Conference number: 2 |
Conference
| Conference | 2nd European Congress of Immunology |
|---|---|
| Number | 2 |
| Country/Territory | Germany |
| City | Berlin |
| Period | 13/09/2009 → 16/09/2009 |