T Lymphocyte Apoptosis in Systemic Lupus Erythematosus Patients

Rastin, Maryam; Mahmoudi, Mahmoud; Hatef, Mohammadreza; Sahebari, Maryam; Tabasi, Nafiseh; Haghmorad, Dariush; Nosratabadi, Reza; Khazaee, Mahdieh; Masoudian, Mitra; Zamani, Shahrzad

doi:10.22038/ijbms.2013.1353

T Lymphocyte Apoptosis in Systemic Lupus Erythematosus Patients

Authors

¹ Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

² 2Rheumatology Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

³ 3Rheumatology Research Center, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

⁴ 1Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

10.22038/ijbms.2013.1353

Abstract

Objective(s): Apoptosis is a tightly regulated process and plays a crucial role in autoimmune diseases. Because abnormalities in apoptosis are considered to be involved in the pathogenesis of systemic lupus erythematosus (SLE), in present study we studied the apoptosis in T lymphocytes from Iranian SLE patientsat protein and gene expression levels for some molecules which are involved in apoptosis pathways.
Materials and Methods: Thirty five SLE patients (23 female, 12 male), and 20 age matched controls (10 female, 10 male) participated in this study. T lymphocytes were isolated from peripheral blood mononuclear cells (PBMCs) using MACS method. Apoptosis rate was studied at protein level by flow cytometer using Annexin V, and at gene expression level using semi-quantitative RT-PCR method for detection of Fas, FasL, Bcl-2, caspase 8, and caspase 9 genes.
Results: The percentage of apoptotic cells in SLE patients was not different in comparison with controls (20.2% ± 1.4 vs 21.1% ± 1.0), but the expression levels of FasL, caspase 8, and caspase 9 genes in all SLE patients and in female patients were significantly lower than controls; 0.45R vs 0.78R for FasL, 0.74R vs 1.0R for caspase 8, and 0.76R vs 1.26R for caspase 9 in all SLE patients and 0.37R vs 0.82R for FasL, 0.45R vs 1.6R for caspase 8, and 0.63R vs 1.56R for caspase 9 in female patients.
Conclusion:The expression levels of FasL, caspase 8 and caspase 9 molecules involved in apoptosis decreased in female, but not in male SLE patients.

Keywords

Apoptosis Autoimmune Gene expression Systemic lupuserythema- tosus

References

1. Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, et al. Development of auto antibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349: 1526-1533.

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

3. Kaplan MJ. Apoptosis in systemic lupus erythematosus. Clin Immunol 2004; 112: 210-218.

4. Wang H, Xu J, Ji X, Yang X, Sun K, Liu X, et al. The abnormal apoptosis of T cell subsets and apoptosis involvement of IL-10 in systemic lupus erythematosus. Cell Immunol 2005; 235: 117-121.

5. Munoz L, Bavel CV, Franz S, Berden J, Hermann M, Van der Vlag J. apoptosis in the pathogenesis of systemic lupus erythematosus. Lupus 2008; 17: 371-375.

6. Reefman E, Horst G, Nijk MT, Limburg PC, Kallenberg CGM, and Bijl M. Opsonization of Late Apoptotic Cells by Systemic Lupus Erythematosus Autoantibodies Inhibits Their Uptake via an Fcg Receptor–Dependent Mechanism. Arthritis Rheum 2007; 56: 3399-3341.

7. Bijl M, Limburg PC, Kallenberg CG .New insight into the pathogenesis of systemic lupus erythematosus (SLE): the role of apoptosis. N J Med 2001; 59: 66-75.

8. Bijl M, Horst G, Limburg PC, Kallenberg CG .Anti-CD3-induced and anti- Fas -induced apoptosis in systemic lupus erythematosus. Clin Exp Immunol 2001; 123: 127-132.

9. Zimmermann KC, Bonzon C, Green DR .The machinery of programmed cell death. Pharmacol Ther 2001; 92: 57-70.

10. Bengtsson AA, Gullstrand B, Truedsson L, Sturfelt G .SLE serum induces classical caspase-dependent apoptosis independent of death receptors. Clin Immunol 2008; 126: 57-66.

11. Krueger A, Fas SC, Baumann S, Krammer PH .The role of CD95 in the regulation of peripheral T-cell apoptosis. Immunol Rev 2003; 193: 58-69.

12. Caricchio R, Cohen PL .Spontaneous and induced apoptosis in systemic lupus erythematosus: multiple assays fail to reveal consistent abnormalities. Cell Immunol 1999; 198: 54-60.

13. Grondal G, Traustadottir KH, Kristjansdottir H, Lundberg I, Klareskog L, Erlendsson K, et al .Increased lymphocyte apoptosis/ necrosis and IL-10 producing cells in patients and their spouses in Icelandic systemic lupus erythematosus multicase families. Lupus 2002; 11: 435-442.

14. Courtney PA, Crockard AD, Williamson K, McConnell J, Kennedy RJ, Bell AL. Lymphocyte apoptosis in systemic lupus erythematosus: relationship with Fas expression, serum soluble Fas and disease activity. Lupus 1999; 8: 508-513.

15. Lorenz HM, Grunke M, Hieronymus T, Hermann M, Kuhnel A, Manger B, et al. In vitro apoptosis and expression of apoptosis- related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases. Arthritis Rheum 1997; 40: 306-317.

16. Ho CY, Wong CK, Li EK, Lam WK. Effects of dexamethasone on the expression of Fas molecules and apoptosis of lymphocytes in patients with systemic lupus erythematosus. Immunol Invest 2001; 30: 231-43.

17. McNally J, Yoo DH, Drappa J, Chu JL, Yagita H, Friedman SM, et al .Fas ligand expression and function in systemic lupus erythematosus. J Immunol 1997; 159: 4628-4636.

18. Maas K, Chan S, Parker J, Slater A, Moore J, Olsen N, et al .Cutting edge; molecular portrait of human autoimmune disease. J Immunol 2002; 169: 5-9.

19. Kovacs B, Liossis SN, Dennis GJ, Tsokos GC. Increased expression of functional Fas-ligand in activated T cells from patients with systemic lupus erythematosus. Autoimmunity 1997; 25: 213-221.

20. Gaipl US, Munoz LE, Grossmayer G, Lauber K, Franz S, Sarter K, et al.Clearance deficiency and systemic lupus erythematosus (SLE). J Autoimmun 2007; 28: 114-121.

21. Grossmayer GE, Munoz LE, Gaipl US, Franz S, Sheriff A, Voll RE, et al .Removal of dying cells and systemic lupus erythematosus. Mod Rheumatol 2005; 15: 383-390.

22. Shao WH, Cohen PL. Disturbances of apoptotic cell clearance in systemic lupus erythematosus. Arthritis Res Ther 2011; 13: 202.

23. Rastin M, Hatef MR, Tabasi N, Mahmoudi M. The pathway of estradiol- induced apoptosis in patients with systemic lupus erythematosus. Clin Rheumatol 2012; 31: 417-424.

24. Rastin M, Hatef MR, Tabasi N, Sheikh A, Morad Abbasi J, Mahmoudi M .Sex hormones and peripheral white blood cells in systemic lupus erythematosus. Iran J Immunol 2007; 4: 110-115.

25. Zandman-Goddard G, Peeva E, Shoenfeld Y. Gender and autoimmunity. Autoimmun Rev 2007; 6: 366-372.