Low Expression Levels of Soluble CD1d Gene in Patients with Rheumatoid Arthritis

SATOSHI KOJO, AKITO TSUTSUMI, DAISUKE GOTO, and TAKAYUKI SUMIDA

ABSTRACT.

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 ß₂ microglobulin, ß₂m) 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 ß₂m 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 ß₂m deleted variants and intact CD1d mRNA.

Conclusion. Our findings suggest that low expression of soluble CD1d variants might play a role in the formation of symptoms or pathogenesis of RA. (J Rheumatol 2003;30:2524-8)

Key Indexing Terms:

ALTERNATIVE SPLICING VARIANT
AUTOIMMUNE DISEASE
CD1D
NATURAL KILLER T CELLS

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From the Division of Rheumatology, Department of Internal Medicine, University of Tsukuba, Tsukuba, Japan.

S. Kojo, PhD; A. Tsutsumi, MD, PhD; D. Goto, MD, PhD; T. Sumida, MD, PhD.

Address reprint requests to Dr. T. Sumida, Division of Rheumatology, Department of Internal Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. E-mail: tsumida@md.tsukuba.ac.jp

Submitted November 27, 2002; revision accepted May 29, 2003.

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