Elevated levels of TRAIL in systemic lupus erythematosus are associated to the presence of anti-SSA/SSB antibodies

Abstract

The objective of this study was to determine potential relationship between the levels of serum TNF-related apoptosis inducing ligand (TRAIL) and osteoprotegerin (OPG) and clinical markers in systemic lupus erythematosus (SLE) patients. Forty SLE patients with inactive disease were enrolled in this study. For comparison, 20 Sjögren's syndrome (SS) patients and 30 normal controls were also analysed. Serum levels of TRAIL and OPG were determined by ELISA. Serum TRAIL and OPG concentrations in SLE patients were significantly (P < 0.05) higher than those in healthy volunteers. Of note, serum TRAIL but not OPG was significantly (P < 0.05) higher in the SLE patient subset characterized by the presence of anti-SSA/SSB antibodies. The relationship between high levels of TRAIL and SSA/SSB antibodies was further supported by the analysis of SS patients characterized by SSA/SSB antibodies positivity, in which TRAIL levels resulted comparable to the subgroup of anti-SSA/SSB positive SLE patients. The presence of SSA/SSB antibodies, targeting a specific subset of SLE and SS patients, is related to increased serum levels of TRAIL but not of OPG. Lupus (2007) 16, 479—482.

Keywords

apoptosis autoantibodies cytokines (TRAIL osteoprotegerin)ELISA SLE

Get full access to this article

View all access options for this article.

References

Gaipl US , Voll RE , Sheriff A. , Franz S. , Kalden JR , Herrmann M. Impaired clearance of dying cells in systemic lupus erythematosus. Autoimmun Rev 2005; 4: 189—194.

White S. , Rosen A. Apoptosis in systemic lupus erythematosus. Curr Opin Rheumatol 2003; 5: 557—562.

Famularo G. , Nucera E. , Marcellini S. , De Simone C. Fas/Fas ligand on the road: an apoptotic pathway common to AIDS, autoimmunity, lymphoproliferation and transplantation. Med Hypotheses 1999; 53: 50—62.

Xue C. , Lan-Lan W, Bei C, Jie C, Wei-Hua F. Abnormal Fas/FasL and caspase-3-mediated apoptotic signaling pathways of T lymphocyte subset in patients with systemic lupus erythematosus. Cell Immunol 2006; 239: 121—128.

Rus V. , Atamas SP , Shustova V. et al. Expression of cytokine- and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array. Clin Immunol 2002; 102: 283—290.

Kaplan MJ , Lewis EE , Shelden EA et al. The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologus lupus T cells. J Immunol 2002; 169: 6020—6029.

Lub-de Hooge MN , De Vries Ege , de Jong S. , Bijl M. Soluble TRAIL concentrations are raised in patients with systemic lupus erythematosus. Ann Rheum Dis 2005; 64: 854—858.

Zauli G. , Secchiero P. The role of the TRAIL/TRAIL receptors system in hemopoiesis and endothelial cell biology. Cytokine & Growth Factor Reviews 2006; 17: 245—257.

Ziolkowska M. , Kurowska M. , Radzikowska A. et al. High levels of osteoprotegerin and soluble receptor activator of Nuclear Factor kB ligand in serum of rheumatoid arthritis patients and their normalization after antitumor necrosis factor α treatment. Arthritis Rheum 2002; 46: 1744—1753.

10.

Choi JW Relationships between tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and hematopoietic activity in healthy adults. Ann Hematol 2005; 84: 728—733.

11.

Liabbakk NB , Espevik T. Development, characterization and use of monoclonal antibodies against sTRAIL: measurement of sTRAIL by ELISA. J Immunol Methods 2002; 259: 119—128.

12.

Matsuyama W. , Yamamoto M. , Higashimoto I. et al. TNF-related apoptosis inducing ligand is involved in neutropenia of systemic lupus erythematosus. Blood 2004; 104: 184—191.

13.

Thompson D. , Juby A. , Davis P. The clinical significance of autoantibody profiles in patients with systemic lupus erythematosus. Lupus 1993; 2: 15—19.

14.

Cretney E. , Shanker A. , Yagita H. , Smyth MJ , Sayers TJ TNF-related apoptosis-inducing ligand as a therapeutic agent in autoimmunity and cancer. Immunol Cell Biol 2006; 84: 87—98.

15.

Kurien BT , Newland J. , Paczkowski C. , Moore KL , Scofield RH Association of neutropenia in systemic lupus erythematosus with anti-Ro and binding of an immunobiologically cross-reactive neutrophil membrane antigen . Clin Exp Immunol 2000; 120: 209—217.

16.

Hsieh SC , Yu HS , Lin WW et al. Anti-SSB/La is one of the antineutrophil autoantibodies responsible for neutropenia and functional impairment of polymorphonuclear neutrophils in patients with systemic lupus erythematosus. Clin Exp Immunol 2003; 131: 396—397.

17.

Lum JJ , Bren G. , McClure R. , Badley AD Elimination of senescent neutrophilis by TNF-related apoptosis-inducing ligand . J Immunology 2005; 175: 1232—1238.