Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to be involved in the pathophysiology of some autoimmune diseases as systemic lupus erythematosus, ankylosing spondylitis, and multiple sclerosis. The aim of this study was to assess serum TRAIL concentration in systemic sclerosis (SSc) patients and to investigate its possible association with various disease parameters. Thirty SSc patients as well as 25 rheumatoid arthritis (RA) patients and 25 healthy volunteers were included in the present study. Organ system involvement in SSc patients was investigated. Pulmonary function tests as well as chest high-resolution computed tomography (HRCT) were done to detect pulmonary involvement in our patients. TRAIL concentrations were measured in the sera of SSc patients, RA patients and healthy controls by enzyme-linked immunosorbent assay. Mean serum TRAIL levels were significantly higher in SSc patients than in the control RA patients and in healthy controls (p < 0.001) while they were not significantly different between patients with diffuse cutaneous SSc and patients with limited cutaneous scleroderma. Serum TRAIL levels were significantly higher in SSc patients with pulmonary involvement and were significantly correlated with HRCT scores. Serum TRAIL levels are significantly elevated in SSc patients and are associated with SSc-associated pulmonary involvement denoting a possible role of TRAIL in the pathogenesis of SSc. Further studies may be needed to confirm these findings and the possible use of TRAIL in detection and possibly treatment of SSc-associated pulmonary disease.
Similar content being viewed by others
References
White B (1996) Immunopathogenesis of systemic sclerosis. Rheum Dis Clin North Am 22:695–708
Krammer PH (2000) CD95’s deadly mission in the immune system. Nature 407:789–795
King C, Ilic A, Koelsch K, Sarvetnick N (2004) Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell 117:265–277
Jelaska A, Korn JH (2000) Role of apoptosis and transforming growth factor beta 1 in fibroblast selection and activation in systemic sclerosis. Arthritis Rheum 43:2230
Wiley SR, Schooley K, Smolak PJ et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3(6):673–682
Le Blanc HN, Ashkenazi A (2003) Apo 2L/TRAIL and its death decoy receptors. Cell Death Differ 10:66–75
Jo M, Kim TH, Seol DW et al (2000) Apoptosis induced in normal human hepatocytes tumour necrosis factor-related apoptosis-inducing ligand. Nat Med 6(5):564–567
Nitsch R, Bechmann I, Deisz RA et al (2000) Human brain-cell death induced by tumour-necrosis factor-related apoptosis-inducing ligand (TRAIL). Lancet 356:827–828
Lub-de Hooge MN, de Vries EG, de Jong S, Bijl M (2005) Soluble TRAIL concentrations are raised in patients with systemic lupus erythematosus. Ann Rheum Dis 64:854–858
Zai-Xing Y, Yan L, Hao W, Ye Z et al (2008) Preliminary clinical measurement of the expression of TNF-related apoptosis inducing ligand in patients with ankylosing spondylitis. J Clin Lab Anal 22(2):138–145
Huang WX, Huang P, Gomes A, Hillert J (2000) Apoptosis mediators FasL and TRAIL are upregulated in peripheral blood mononuclear cells in MS. Neurology 55:928–934
Preliminary criteria for the classification of systemic sclerosis (scleroderma): Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and therapeutic Criteria Committee (1980) Arthritis Rheum 23:581–590
Le Roy EC, Black C, Fleischmajer R et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205
Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Clements PJ, Lachenbruch PA, Seibold JR et al (1993) Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol 20:1892–1896
Warrick JH, Bhalla M, Schabel SI, Silver RM (1991) High resolution computed tomography in early scleroderma lung disease. J Rheumatol 18:1520–1528
Valat C, Diot E, Diot P (1998) Serum III procollagen is predictive of lung involvement in systemic sclerosis, but not serum I procollagen. Clin Exp Rheumatol 16:517–518
Martin SJ, Grenn DR, Cotter TG (1994) Dicing with death: dissecting the components of the apoptosis machinery. Trends Biochem Sci 19:26–29
Kessel A, Rosner I, Rozenbaum M et al (2004) Increased CD8+ T cell apoptosis in scleroderma is associated with low levels of NF-kappa B. J Clin Immunol 24:30–36
Tsai HF, Lai JJ, Chou AH et al (2004) Induction of costimulation of human CD4 T cells by tumor necrosis factor-related apoptosis-inducing ligand: possible role in T cell activation in systemic lupus erythematosus. Arthritis Rheum 50(2):629–639
Matsumura R, Umemiya K, Kagami M et al (2002) Expression of TNF-related apoptosis inducing ligand (TRAIL) on infiltrating cells and of TRAIL receptors on salivary glands in patients with Sjogren’s syndrome. Clin Exp Rheumatol 20:791–798
Kaplan MJ, Lewis EE, Shelden EA et al (2002) The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells. J Immunol 169:6020–6029
Rus V, Atamas SP, Shustova V et al (2002) Expression of cytokine- and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array. Clin Immunol 102:283–290
Matsuyama W, Yamamoto M, Higashimoto I et al (2004) TNF related apoptosis inducing ligand is involved in neutropenia of systemic lupus erythematosus. Blood 104:184–191
Yurovsky VV (2004) Cross-talk between TRAIL and TGF-β in regulation of collagen production in scleroderma lung disease. Arthritis Res Ther 6(Suppl 1):26
Diot E, Boissinot E, Asquier E et al (1998) Relationship between abnormalities on high resolution computed tomography and pulmonary function in systemic sclerosis. Chest 114:1623–1629
Bouros D, Wells AU, Nicholson AG et al (2002) Histopathologic subset of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med 165:1581–1586
Tomasek JJ, Gabbiani G, Hinz B et al (2002) Myofibroblasts and mechano-regulation of connective tissue remodeling. Nat Rev Mol Cell Biol 3:349–363
Harrison NK, Myers AR, Corrin B et al (1991) Structural features of interstitial lung disease in systemic sclerosis. Am Rev Respir Dis 144(3 Pt 1):706–713
Yurovsky VV (2003) Tumor necrosis factor-related apoptosis-inducing ligand enhances collagen production by human lung fibroblasts. Am J Respir Cell Mol Biol 28:225–231
Atamas SP, Yurovsky VV, Wise R, Wigley FM, Goter Robinson CJ, Henry P, Alms WJ, White B (1999) Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum 42:1168–1178
Freiberg RA, Spencer DM, Choate KA, Duh HJ, Schreiber SL, Crabtree GR, Khavari PA (1997) Fas signal transduction triggers either proliferation or apoptosis in human fibroblasts. J Invest Dermatol 108:215–219
Chou AH, Tsai HF, Lin LL et al (2001) Enhanced proliferation and increased IFN-production in T cells by signal transduced through TNF-related apoptosis-inducing ligand. J Immunol 167:1347–1352
Halaas O, Vik R, Ashkenazi A, Espevik T (2000) Lipopolysaccharide induces expression of APO2 ligand/TRAIL in human monocytes and macrophages. Scand J Immunol 51:244–250
Luzina I, Atamas S, Lockatell L, Rus V (2011) CCL18-mediated pulmonary infiltration of T lymphocytes is independent of TRAIL but requires DR5. J Immunol 186:102.20
Fries KM, Blieden T, Looney RJ et al (1994) Evidence of fibroblast heterogeneity and the role of fibroblast subpopulations in fibrosis. Clin Immunol Immunopathol 72:283–292
Disclosures
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Azab, N.A., Rady, H.M. & Marzouk, S.A. Elevated serum TRAIL levels in scleroderma patients and its possible association with pulmonary involvement. Clin Rheumatol 31, 1359–1364 (2012). https://doi.org/10.1007/s10067-012-2023-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-012-2023-3