RT Journal Article
SR Electronic
T1 DcR3 Mutations in Patients with Juvenile-onset Systemic Lupus Erythematosus Lead to Enhanced Lymphocyte Proliferation
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.121285
DO 10.3899/jrheum.121285
A1 Chayanin Chokdeemeeboon
A1 Pramuk Ammarinthnukrowh
A1 Siraprapa Tongkobpetch
A1 Chalurmpon Srichomtong
A1 Tawatchai Deekajorndech
A1 Pornpimol Rianthavorn
A1 Pornchai Kingwattanakul
A1 Yingyos Avihingsanon
A1 Helen L.  Wright
A1 Piyaporn Akkahat
A1 Voravee P.  Hoven
A1 Wanwimon Mekboonsonglarp
A1 Steven W.  Edwards
A1 Nattiya Hirankarn
A1 Kanya Suphapeetiporn
A1 Vorasuk Shotelersuk
YR 2013
UL http://www.jrheum.org/content/early/2013/05/29/jrheum.121285.abstract
AB Objective Previous studies suggested a role for the death decoy receptor 3 (DcR3) in the pathogenesis of adult systemic lupus erythematosus (SLE). We investigated the role of DcR3 in juvenile-onset SLE, to identify polymorphisms that might alter the function of this protein. Methods DcR3 was measured in the serum of 61 patients with juvenile SLE. The coding region of the DcR3 gene was sequenced in 100 juvenile and 103 adult patients with SLE, together with 500 healthy controls. Results DcR3 was elevated in the serum of juvenile patients with active SLE disease (440.8 ± 169.1 pg/ml), compared to patients with inactive disease (122.6 ± 28.05 pg/ml; p = 0.0014) and controls (69.27 ± 20.23 pg/ml; p = 0.0009). DNA sequencing identified 2 novel missense mutations: c.C167T (p.T56I) in an adult SLE patient and c.C364T (p.H122Y) in a juvenile patient. Recombinant proteins containing these mutations exhibited altered binding kinetics to FasL and they significantly increased lymphocyte proliferation, compared to the wild-type protein (p < 0.05). The adult patient with SLE carrying the p.T56I mutation had significantly increased lymphocyte proliferation compared to 3 SLE controls matched for age, sex, and disease severity. Conclusion DcR3 may play an etiologic role in SLE through either elevated serum levels of wild-type DcR3 or normal levels of gain-of-function DcR3 proteins that increase lymphocyte proliferation.