DcR3 as a diagnostic parameter and risk factor for systemic lupus erythematosus.
In this study, we investigated the diagnostic value of serum death decoy receptor 3 (DcR3) for systemic lupus erythematosus (SLE). The possible pathogenic role of DcR3 in SLE was also assessed. Serum DcR3 levels of 90 SLE patients, 11 patients with rheumatic conditions and 123 healthy controls were determined by ELISA. In all, 43% of the SLE patients, 9% of patients with rheumatic conditions and 2.4% of the normal healthy individuals presented elevated serum DcR3 levels. A higher percentage of DcR3-positive SLE patients, compared with DcR3-negative SLE patients, showed abnormally high serum IgE levels, a surrogate marker of T(h)2-type immune responses. To determine the cause and effect relationship of DcR3 expression and a T(h)2-prone status, we studied young DcR3 transgenic (Tg) mice, whose transgene was driven by an actin promoter. These mice had IL-4 overproduction and augmented serum IgE levels, signs of dominant T(h)2 immune responses. To determine possible SLE pathogenic roles of DcR3, the T-cell-depleted bone marrow of DcR3 Tg mice was transplanted into lethally irradiated syngeneic C57BL/6 female mice. The recipients developed an SLE-like syndrome. They presented anti-dsDNA and anti-nuclear antibodies, along with renal and liver pathology compatible with that of SLE. In total, 90% of Tg bone marrow-transplanted mice, compared with 20% of wild-type bone marrow-transplanted mice, perished within 12 months after the transplantation. Our results showed that serum DcR3 could serve as an additional parameter for SLE diagnosis and that DcR3 secreted from cells of hematopoietic origin was SLE pathogenic in mice.
Laboratory of Immunology, Research Centre, Centre hospitalier de l'Université de Montréal, Notre-Dame Hospital, Pavilion DeSève, Montreal, Quebec H2L 4M1, Canada.
Bing
B
Han
Rafael
R
Bojalil
Luis M
LM
Amezcua-Guerra
Rashidi
R
Springall
Héctor
H
Valderrama-Carvajal
Jiangping
J
Wu
Hongyu
H
Luo
D000293:Adolescent; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D016026:Bone Marrow Transplantation; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D012737:Sex Factors; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018183:Transplantation Chimera
D001323:Autoantibodies; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; D015847:Interleukin-4; D007073:Immunoglobulin E