Low expression levels of soluble CD1d gene in patients with rheumatoid arthritis.
OBJECTIVE
To examine whether the expression of intact CD1d, a critical molecule for the presentation of glycolipid antigens to natural killer T (NKT) cells, and its variants differs between patients with autoimmune diseases including rheumatoid arthritis (RA) and healthy subjects. Recently, we identified 8 different CD1d variants, generated by alternative splicing. V1 lacking exon 4 (CD1d without beta2 microglobulin, beta2m) and V2 lacking exons 4 and 5 (soluble CD1d) may be functional molecules, because the antigen binding sites (exons 2 and 3) are intact.


METHODS
Peripheral blood mononuclear cells (PBMC) from 44 patients with autoimmune disease (RA 19, systemic lupus erythematosus, SLE 10, Sjögren's syndrome, SS 15) and 15 healthy controls were separated and complementary (c)DNA was prepared. The expression of intact CD1d on PBMC was detected by flow cytometry. Alternatively spliced CD1d variants were quantified by TaqMan PCR using polymerase chain reaction with confronting 2-pair primers (PCR-CTPP) based amplification.


RESULTS
The mean (+/- SEM) transmembrane and beta2m binding site deleted CD1d mRNA level in 19 patients with RA (2.0 +/- 0.33) was significantly lower than in 15 controls (6.9 +/- 2.08; p < 0.05), whereas there were no differences in beta2m deleted variants and intact CD1d mRNA.


CONCLUSIONS
Our findings suggest that low expression of soluble CD1d variants might play a role in the formation of symptoms or pathogenesis of RA.
Kojo
Satoshi
S
Division of Rheumatology, Department of Internal Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Tsutsumi
Akito
A
Goto
Daisuke
D
Sumida
Takayuki
T
D017398:Alternative Splicing; D018949:Antigens, CD1 / Q000235:genetics* / Q000378:metabolism; D055610:Antigens, CD1d; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000097:blood*; D018076:DNA, Complementary / Q000032:analysis / Q000097:blood; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics; D019914:Taq Polymerase / Q000378:metabolism
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D018076:DNA, Complementary; D020033:Protein Isoforms; D019914:Taq Polymerase