The Study of Relationship between Serum Levels of Soluble fms-like Tyrosine Kinase-1 and Soluble Fibrinogen-like Protein 2 with Delayed Graft Function after Kidney Transplantation
-
Hossein Akbari
,
Zahra Hooshyar
,
Saeede Shabanitabar
,
Ali Salmani
,
Hassan Nikoueinejad
,
Behzad Einollahi
Abstract
Delayed graft function (DGF) is a transplant complication which means a need to dialysis throughout the first week after transplantation. This study aimed to ascertain the relationship between the two immunomodulatory factors of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble fibrinogen-like protein 2 (sFGL-2) with DGF after transplantation. This case-control study was done in 2 groups of 58 kidney transplant patients with and without DGF. The control group included the patients who didn’t show DGF symptoms. Then, serum levels of sFlt-1and sFGL-2 in all blood samples were measured by ELISA. Serum sFlt-1 and sFGL-2 levels were significantly higher in the DGF group compared to those in the control group (p≤0.001). sFlt-1 and sFGL-2 serum levels significantly affect DGF (p<0.001) in such a way that they may be diagnostic factors of DGF. This study showed a significant relationship between sFlt-1 as well as sFGL-2 and DGF. Therefore, plasma levels of sFlt-1 and sFGL-2 may be used as diagnostic tools to determine the risk of DGF.
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6. Tuder RM, Flook BE, Voelkel NF. Increased gene expression for VEGF and the VEGF receptors KDR/flk and flt in lungs exposed to acute or chronic hypoxia. J Clin Invest 1995; 95(4):1798-807.
7. Roberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J cell Sci 1995; 108(6):2369-79
8. Schweighofer B, Testori J, Sturtzel C, Sattler S, Mayer H, Wagner O, et al. The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation. Thromb Haemost 2009; 102(3):544-54.
9. Ataga KI, Brittain JE, Jones SK, May R, Delaney J, Strayhorn D,et al. Association of soluble fms-like tyrosine kinase-1 with pulmonary hypertension and haemolysis in sickle cell disease. Br J Haematol 2011; 152(4):485-91.
10. Kulkarni1 A, Mehendale S, YadavH, KilariA, Taralekar V, Joshi S. Circulating angiogenic factors and their association with birth outcomes in preeclampsia. Hypertens Res 2010; 33(6):561-7.
11. Shalev I, Liu H, Koscik C, Bartczak A, Javadi M, Wong KM, et al. Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis. J Immunol 2008; 180(1):249-60.
12. Li XL, Ménoret S, Bezie S, Caron L, Chabannes D, Hill M, et al. Mechanism and localization of CD8 regulatory T cells in a heart transplant model of tolerance. J Immunol 2010; 185(2):823-33.
13. Wang L, Yang C, Xu M, Hu M, Wang X, Zhu T. The Role of Soluble Fibrinogen-Like Protein 2 in Transplantation: Protection or Damage. Transplantation 2014; 97(12):1201-6.
14. Selzner N, Liu H, Boehnert MU, Adeyi OA, Shalev I, Bartczak AM, et al. FGL2/fibroleukin mediates hepatic reperfusion injury by induction of sinusoidal endothelial cell and hepatocyte apoptosis in mice. J Hepatol 2012; 56(1):153-9.
15. Radeke HH, Janssen-Graalfs I, Sowa EN, et al. Opposite regulation of type II and III receptors for immunoglobulin G in mouse glomerular mesangial cells and in the induction of anti-glomerular basement membrane (GBM) nephritis. J Biol Chem 2002; 277(30):27535-44.
16. Liu H, Zhang L, Cybulsky M, Gorczynski R, Crookshank J, Manuel J, et al. Identification of the receptor for FGL2 and implications for susceptibility to mouse hepatitis virus (MHV-3)-induced fulminant hepatitis. Adv Exp Med Biol 2006; 581:421-5.
17. Zhao Z, Wang L, Yang C, Zhao T, Li L, Hu L, et al. Soluble FGL2 induced by tumor necrosis factor-α and interferon-γ in CD4+ T cells through MAPK pathway in human renal allograft acute rejection. J Surg Res 2013; 184(2):1114-22.
18. Foerster K, Helmy A, Zhu Y, Khattar R, Adeyi OA, Wong KM, Shalev I, Clark DA, Wong PY, Heathcote EJ, Phillips MJ, Grant DR, Renner EL, Levy GA, Selzner N. The novel immunoregulatory molecule FGL2: a potential biomarker for severity of chronic hepatitis C virus infection. J Hepatol 2010; 53(4):608–15.
19. Xie L, Ichimaru N, Morita M, Chen J, Zhu P, Wang J, et al. Identification of a novel biomarker gene set with sensitivity and specificity for distinguishing between allograft rejection and tolerance. Liver Transpl 2012; 18(4):444–5429.
20. Zhao Z, Yang C, Tang Q, Zhao T, Jia Y, Ma Z, et al. Serum level of soluble fibrinogen-like protein 2 in renal allograft recipients with acute rejection: a preliminary study. Transplant Proc 2012; 44(10):2982-5.
21. Liu H, Shalev I, Manuel J, He W, Leung E, Crookshank J, et al. The FGL2‐FcγRIIB pathway: A novel mechanism leading to immunosuppression. European journal of immunology 2008; 38(11):3114-26.
22. Zhang N, Schröppel B, Lal G, Jakubzick C, Mao X, Chen D, et al. Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response. Immunity 2009;30(3):458-69.
23. Chapal M, Néel M, Le Borgne F, Meffray E, Carceles O, Hourmant M, et al. Increased Soluble Flt-1 Correlates With Delayed Graft Function and Early Loss of Peritubular Capillaries in the Kidney Graft. Transplantation 2013; 96(8):739-44.
24. Krenn K1, Klepetko W, Taghavi S, Lang G, Schneider B, Aharinejad S,et al. Recipient vascular endothelial growth factor serum levels predict primary lung graft dysfunction.Transplantation 2007; 7(3):700-6.
25. Takayama K, Ueno H, Nakanishi Y, Sakamoto T, Inoue K, Shimizu K, et al. Suppression of tumor angiogenesis
and growth by gene transfer of a soluble form of vascular endothelial growth factor receptor into a remote organ. Cancer Res 2000; 60(8):2169-77.
26. Honda M, Sakamoto T, Ishibashi T, Inomata H, Ueno H. Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection: a role of VEGF and possible treatment for SRN in age-related macular degeneration. Gene Ther 2000; 7(11):978-85.
27. Zhu C-S, Hu X-Q, Xiong Z-J, Lu Z-Q, Zhou G-Y, Wang D-J. Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental autoimmune encephalomyelitis in dark Agouti (DA) rats. Life Sci 2008; 83(11):404-12.
28. Hayashi T1, Usui T, Yamagami S.Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation.Tohoku J Exp Med 2016; 239(1):81-8.
29. Miotla J, Maciewicz R, Kendrew J, Feldmann M, Paleolog E. Treatment with soluble VEGF receptor reduces disease severity in murine collagen-induced arthritis. Lab Invest 2000; 80(8):1195-205.
30. Zhao Z, Yang C, Tang Q, Zhao T, Jia Y, Ma Z, et al. Serum level of soluble fibrinogen-like protein 2 in renal allograft recipients with acute rejection: a preliminary study. Transplant Proc 2012; 44(10):2982-5.
31. Ning Q, Sun Y, Han M, et al. Role of fibrinogen-like protein 2 prothrombinase/fibroleukin in experimental and human allograft rejection. J Immunol 2005; 174(11):7403-11.
32. Aquino-Dias EC, Joelsons G, da Silva DM, Berdichevski RH, Ribeiro AR, Veronese FJ, Goncalves LF, Manfro RC. Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function. Kidney Int 2008; 73(7):877–84
33. Taflin C, Nochy D, Hill G, Frouget T, Rioux N, Verine J, Bruneval P, Glotz D. Regulatory T cells in kidney allograft infiltrates correlate with initial inflammation and graft function. Transplantation 2010; 89(2):194–9.
34. Wei S, Kryczek I, Zou W. Regulatory T-cell compartmentalization and trafficking. Blood 2006; 108(2):426-31.
35. Zhang N, Schröppel B, Lal G, Jakubzick C, Mao X, Chen D, et al. Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response. Immunity 2009; 30(3):458-69.
36. Lieberthal W, Koh JS, Levine JS. Necrosis and apoptosis in acute renal failure. Semin Nephrol 1998; 18(5):505-18
2. Moore J, shabir S, Chand S, Bentall A, McClean A, Chan W, et al. Assessing and comparing rival definitions of delayed renal allograft function for predicting subsequent graft failure. Transplantation 2010; 90(10):1113-6.
3. Holmes K, Roberts OL, Thomas AM, Cross MJ .Vascular endothelial growth factor receptor-2: structure, function, intracellular signaling and therapeutic inhibition. Cell Signal 2007; 19(10):2003-12.
4. Danovitch G. Handbook of kidney transplantation. 4th ed. Philadelphia, LipimcottWilliams &Wilkins; 2005.
5. Ribatti D, Tamma R. Hematopoietic growth factors and tumor angiogenesis. Cancer Lett 2018; 50304-3835(18):30614-1.
6. Tuder RM, Flook BE, Voelkel NF. Increased gene expression for VEGF and the VEGF receptors KDR/flk and flt in lungs exposed to acute or chronic hypoxia. J Clin Invest 1995; 95(4):1798-807.
7. Roberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J cell Sci 1995; 108(6):2369-79
8. Schweighofer B, Testori J, Sturtzel C, Sattler S, Mayer H, Wagner O, et al. The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation. Thromb Haemost 2009; 102(3):544-54.
9. Ataga KI, Brittain JE, Jones SK, May R, Delaney J, Strayhorn D,et al. Association of soluble fms-like tyrosine kinase-1 with pulmonary hypertension and haemolysis in sickle cell disease. Br J Haematol 2011; 152(4):485-91.
10. Kulkarni1 A, Mehendale S, YadavH, KilariA, Taralekar V, Joshi S. Circulating angiogenic factors and their association with birth outcomes in preeclampsia. Hypertens Res 2010; 33(6):561-7.
11. Shalev I, Liu H, Koscik C, Bartczak A, Javadi M, Wong KM, et al. Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis. J Immunol 2008; 180(1):249-60.
12. Li XL, Ménoret S, Bezie S, Caron L, Chabannes D, Hill M, et al. Mechanism and localization of CD8 regulatory T cells in a heart transplant model of tolerance. J Immunol 2010; 185(2):823-33.
13. Wang L, Yang C, Xu M, Hu M, Wang X, Zhu T. The Role of Soluble Fibrinogen-Like Protein 2 in Transplantation: Protection or Damage. Transplantation 2014; 97(12):1201-6.
14. Selzner N, Liu H, Boehnert MU, Adeyi OA, Shalev I, Bartczak AM, et al. FGL2/fibroleukin mediates hepatic reperfusion injury by induction of sinusoidal endothelial cell and hepatocyte apoptosis in mice. J Hepatol 2012; 56(1):153-9.
15. Radeke HH, Janssen-Graalfs I, Sowa EN, et al. Opposite regulation of type II and III receptors for immunoglobulin G in mouse glomerular mesangial cells and in the induction of anti-glomerular basement membrane (GBM) nephritis. J Biol Chem 2002; 277(30):27535-44.
16. Liu H, Zhang L, Cybulsky M, Gorczynski R, Crookshank J, Manuel J, et al. Identification of the receptor for FGL2 and implications for susceptibility to mouse hepatitis virus (MHV-3)-induced fulminant hepatitis. Adv Exp Med Biol 2006; 581:421-5.
17. Zhao Z, Wang L, Yang C, Zhao T, Li L, Hu L, et al. Soluble FGL2 induced by tumor necrosis factor-α and interferon-γ in CD4+ T cells through MAPK pathway in human renal allograft acute rejection. J Surg Res 2013; 184(2):1114-22.
18. Foerster K, Helmy A, Zhu Y, Khattar R, Adeyi OA, Wong KM, Shalev I, Clark DA, Wong PY, Heathcote EJ, Phillips MJ, Grant DR, Renner EL, Levy GA, Selzner N. The novel immunoregulatory molecule FGL2: a potential biomarker for severity of chronic hepatitis C virus infection. J Hepatol 2010; 53(4):608–15.
19. Xie L, Ichimaru N, Morita M, Chen J, Zhu P, Wang J, et al. Identification of a novel biomarker gene set with sensitivity and specificity for distinguishing between allograft rejection and tolerance. Liver Transpl 2012; 18(4):444–5429.
20. Zhao Z, Yang C, Tang Q, Zhao T, Jia Y, Ma Z, et al. Serum level of soluble fibrinogen-like protein 2 in renal allograft recipients with acute rejection: a preliminary study. Transplant Proc 2012; 44(10):2982-5.
21. Liu H, Shalev I, Manuel J, He W, Leung E, Crookshank J, et al. The FGL2‐FcγRIIB pathway: A novel mechanism leading to immunosuppression. European journal of immunology 2008; 38(11):3114-26.
22. Zhang N, Schröppel B, Lal G, Jakubzick C, Mao X, Chen D, et al. Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response. Immunity 2009;30(3):458-69.
23. Chapal M, Néel M, Le Borgne F, Meffray E, Carceles O, Hourmant M, et al. Increased Soluble Flt-1 Correlates With Delayed Graft Function and Early Loss of Peritubular Capillaries in the Kidney Graft. Transplantation 2013; 96(8):739-44.
24. Krenn K1, Klepetko W, Taghavi S, Lang G, Schneider B, Aharinejad S,et al. Recipient vascular endothelial growth factor serum levels predict primary lung graft dysfunction.Transplantation 2007; 7(3):700-6.
25. Takayama K, Ueno H, Nakanishi Y, Sakamoto T, Inoue K, Shimizu K, et al. Suppression of tumor angiogenesis
and growth by gene transfer of a soluble form of vascular endothelial growth factor receptor into a remote organ. Cancer Res 2000; 60(8):2169-77.
26. Honda M, Sakamoto T, Ishibashi T, Inomata H, Ueno H. Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection: a role of VEGF and possible treatment for SRN in age-related macular degeneration. Gene Ther 2000; 7(11):978-85.
27. Zhu C-S, Hu X-Q, Xiong Z-J, Lu Z-Q, Zhou G-Y, Wang D-J. Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental autoimmune encephalomyelitis in dark Agouti (DA) rats. Life Sci 2008; 83(11):404-12.
28. Hayashi T1, Usui T, Yamagami S.Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation.Tohoku J Exp Med 2016; 239(1):81-8.
29. Miotla J, Maciewicz R, Kendrew J, Feldmann M, Paleolog E. Treatment with soluble VEGF receptor reduces disease severity in murine collagen-induced arthritis. Lab Invest 2000; 80(8):1195-205.
30. Zhao Z, Yang C, Tang Q, Zhao T, Jia Y, Ma Z, et al. Serum level of soluble fibrinogen-like protein 2 in renal allograft recipients with acute rejection: a preliminary study. Transplant Proc 2012; 44(10):2982-5.
31. Ning Q, Sun Y, Han M, et al. Role of fibrinogen-like protein 2 prothrombinase/fibroleukin in experimental and human allograft rejection. J Immunol 2005; 174(11):7403-11.
32. Aquino-Dias EC, Joelsons G, da Silva DM, Berdichevski RH, Ribeiro AR, Veronese FJ, Goncalves LF, Manfro RC. Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function. Kidney Int 2008; 73(7):877–84
33. Taflin C, Nochy D, Hill G, Frouget T, Rioux N, Verine J, Bruneval P, Glotz D. Regulatory T cells in kidney allograft infiltrates correlate with initial inflammation and graft function. Transplantation 2010; 89(2):194–9.
34. Wei S, Kryczek I, Zou W. Regulatory T-cell compartmentalization and trafficking. Blood 2006; 108(2):426-31.
35. Zhang N, Schröppel B, Lal G, Jakubzick C, Mao X, Chen D, et al. Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response. Immunity 2009; 30(3):458-69.
36. Lieberthal W, Koh JS, Levine JS. Necrosis and apoptosis in acute renal failure. Semin Nephrol 1998; 18(5):505-18
| Files | ||
| Issue | Vol 18, No 4 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v18i4.1419 | |
| PMID | 31522449 | |
| Keywords | ||
| Delayed graft function Kidney transplantation Soluble VEGF receptor-1 Soluble fibrinogen-like protein 2 | ||
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How to Cite
1.
Akbari H, Hooshyar Z, Shabanitabar S, Salmani A, Nikoueinejad H, Einollahi B. The Study of Relationship between Serum Levels of Soluble fms-like Tyrosine Kinase-1 and Soluble Fibrinogen-like Protein 2 with Delayed Graft Function after Kidney Transplantation. Iran J Allergy Asthma Immunol. 2019;18(4):412-418.
