IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Circulating Levels of Adipokines Predict the Occurrence of Acute Graft-versus-host Disease

  • Kim, Jin Sook (Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • You, Da-Bin (Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lim, Ji-Young (Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Lee, Sung-Eun (Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Yoo-Jin (Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Hee-Je (Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Chung, Nack-Gyun (Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Min, Chang-Ki (Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2014.10.27
  • Accepted : 2014.12.22
  • Published : 2015.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Currently, detecting biochemical differences before and after allogeneic stem cell transplantation (SCT) for improved prediction of acute graft-versus-host disease (aGVHD) is a major clinical challenge. In this pilot study, we analyzed the kinetics of circulating adipokine levels in patients with or without aGVHD before and after allogeneic SCT. Serum samples were obtained and stored at $-80^{\circ}C$ within 3 hours after collection, prior to conditioning and at engraftment after transplantation. A protein array system was used to measure the levels of 7 adipokines of patients with aGVHD (n=20) and without aGVHD (n=20). The resistin level at engraftment was significantly increased (p<0.001) after transplantation, regardless of aGVHD occurrence. In the non-aGVHD group, the concentrations of the hepatocyte growth factor (HGF) (mean values${\pm}$SD; $206.6{\pm}34.3$ vs. $432.3{\pm}108.9pg/ml$, p=0.040) and angiopoietin-2 (ANG-2) (mean values${\pm}$SD; $3,197.2{\pm}328.3$ vs. $4,471.8{\pm}568.4pg/ml$, p=0.037) at engraftment were significantly higher than those of the pre-transplant period, whereas in the aGVHD group, the levels of adipokines did not change after transplantation. Our study suggests that changes in serum HGF and ANG-2 levels could be considered helpful markers for the subsequent occurrence of aGVHD.

Keywords

References

  1. Coghill, J. M., S. Sarantopoulos, T. P. Moran, W. J. Murphy, B. R. Blazar, and J. S. Serody. 2011. Effector $CD4^+$ T cells, the cytokines they generate, and GVHD: something old and something new. Blood 117: 3268-3276. https://doi.org/10.1182/blood-2010-12-290403
  2. Roy, J., B. R. Blazar, L. Ochs, and D. J. Weisdorf. 1995. The tissue expression of cytokines in human acute cutaneous graft-versus-host disease. Transplantation 60: 343-348. https://doi.org/10.1097/00007890-199508270-00008
  3. Tanaka, J., M. Imamura, M. Kasai, N. Masauzi, A. Matsuura, H. Ohizumi, K. Morii, Y. Kiyama, T. Naohara, M. Saitho, T. Higa, K. Honke, S. Gasa, K. Sakurada, and T. Miyazaki. 1993. Cytokine gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation. Br. J. Haematol. 85: 558-565.
  4. Carayol, G., J. H. Bourhis, M. Guillard, J. Bosq, C. Pailler, L. Castagna, J. P. Vernant, J. L. Pico, M. Hayat, S. Chouaib, and A. Caignard. 1997. Quantitative analysis of T helper 1, T helper 2, and inflammatory cytokine expression in patients after allogeneic bone marrow transplantation: relationship with the occurrence of acute graft-versus-host disease. Transplantation 63: 1307-1313. https://doi.org/10.1097/00007890-199705150-00019
  5. Faaij, C. M., A. C. Lankester, E. Spierings, M. Hoogeboom, E. P. Bowman, M. Bierings, T. Revesz, R. M. Egeler, M. J. van Tol, and N. E. Annels. 2006. A possible role for CCL27/CTACK-CCR10 interaction in recruiting CD4 T cells to skin in human graft-versus-host disease. Br. J. Haematol. 133: 538-549. https://doi.org/10.1111/j.1365-2141.2006.06058.x
  6. Bossard, C., F. Malard, J. Arbez, P. Chevallier, T. Guillaume, J. Delaunay, J. F. Mosnier, P. Tiberghien, P. Saas, M. Mohty, and B. Gaugler. 2012. Plasmacytoid dendritic cells and Th17 immune response contribution in gastrointestinal acute graftversus-host disease. Leukemia 26: 1471-1474. https://doi.org/10.1038/leu.2012.41
  7. Ratajczak, P., A. Janin, L. R. Peffault de, C. Leboeuf, A. Desveaux, K. Keyvanfar, M. Robin, E. Clave, C. Douay, A. Quinquenel, C. Pichereau, P. Bertheau, J. Y. Mary, and G. Socie. 2010. Th17/Treg ratio in human graft-versus-host disease. Blood 116: 1165-1171. https://doi.org/10.1182/blood-2009-12-255810
  8. Fantuzzi, G. 2005. Adipose tissue, adipokines, and inflammation. J. Allergy Clin. Immunol. 115: 911-919. https://doi.org/10.1016/j.jaci.2005.02.023
  9. Min, C. K., S. Y. Kim, M. J. Lee, K. S. Eom, Y. J. Kim, H. J. Kim, S. Lee, S. G. Cho, D. W. Kim, J. W. Lee, W. S. Min, C. C. Kim, and C. S. Cho. 2006. Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation. Bone Marrow Transplant. 38: 149-156. https://doi.org/10.1038/sj.bmt.1705410
  10. Cho, B. S., S. E. Lee, H. H. Song, J. H. Lee, S. A. Yahng, K. S. Eom, Y. J. Kim, H. J. Kim, S. Lee, C. K. Min, S. G. Cho, D. W. Kim, J. W. Lee, W. S. Min, and C. W. Park. 2012. Graft-versus-tumor effect according to type of graft-versus-host disease defined by National Institutes of Health consensus criteria and associated outcomes. Biol. Blood Marrow Transplant. 18: 1136-1143. https://doi.org/10.1016/j.bbmt.2012.01.010
  11. Kwon, H., and J. E. Pessin. 2013. Adipokines mediate inflammation and insulin resistance. Front. Endocrinol. (Lausanne) 4: 71.
  12. Fantuzzi, G. 2013. Adiponectin in inflammatory and immune-mediated diseases. Cytokine 64: 1-10. https://doi.org/10.1016/j.cyto.2013.06.317
  13. Antin, J. H. 2001. Acute graft-versus-host disease: inflammation run amok? J. Clin. Invest 107: 1497-1498. https://doi.org/10.1172/JCI13259
  14. Penack, O., E. Henke, D. Suh, C. G. King, O. M. Smith, I. K. Na, A. M. Holland, A. Ghosh, S. X. Lu, R. R. Jenq, C. Liu, G. F. Murphy, T. T. Lu, C. May, D. A. Scheinberg, D. C. Gao, V. Mittal, G. Heller, R. Benezra, and M. R. van den Brink. 2010. Inhibition of neovascularization to simultaneously ameliorate graft-vs-host disease and decrease tumor growth. J. Natl. Cancer Inst. 102: 894-908. https://doi.org/10.1093/jnci/djq172
  15. Biedermann, B. C., S. Sahner, M. Gregor, D. A. Tsakiris, C. Jeanneret, J. S. Pober, and A. Gratwohl. 2002. Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease. Lancet 359: 2078-2083. https://doi.org/10.1016/S0140-6736(02)08907-9
  16. Biedermann, B. C., D. A. Tsakiris, M. Gregor, J. S. Pober, and A. Gratwohl. 2003. Combining altered levels of effector transcripts in circulating T cells with a marker of endothelial injury is specific for active graft-versus-host disease. Bone Marrow Transplant. 32: 1077-1084. https://doi.org/10.1038/sj.bmt.1704258
  17. Lobov, I. B., P. C. Brooks, and R. A. Lang. 2002. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc. Natl. Acad. Sci. U. S. A. 99: 11205-11210. https://doi.org/10.1073/pnas.172161899
  18. Gohda, E., H. Tsubouchi, H. Nakayama, S. Hirono, O. Sakiyama, K. Takahashi, H. Miyazaki, S. Hashimoto, and Y. Daikuhara. 1988. Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure. J. Clin. Invest. 81: 414-419. https://doi.org/10.1172/JCI113334
  19. Miyazawa, K., H. Tsubouchi, D. Naka, K. Takahashi, M. Okigaki, N. Arakaki, H. Nakayama, S. Hirono, O. Sakiyama, K. Takahashi, E. Gohda, Y. Daikuhara, and N. Kitamura. 1989. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem. Biophys. Res. Commun. 163: 967-973. https://doi.org/10.1016/0006-291X(89)92316-4
  20. Imado, T., T. Iwasaki, Y. Kataoka, T. Kuroiwa, H. Hara, J. Fujimoto, and H. Sano. 2004. Hepatocyte growth factor preserves graft-versus-leukemia effect and T-cell reconstitution after marrow transplantation. Blood 104: 1542-1549. https://doi.org/10.1182/blood-2003-12-4309
  21. Kuroiwa, T., E. Kakishita, T. Hamano, Y. Kataoka, Y. Seto, N. Iwata, Y. Kaneda, K. Matsumoto, T. Nakamura, T. Ueki, J. Fujimoto, and T. Iwasaki. 2001. Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function. J. Clin. Invest. 107: 1365-1373. https://doi.org/10.1172/JCI11808
  22. Berger, M., E. Signorino, M. Muraro, P. Quarello, E. Biasin, F. Nesi, E. Vassallo, and F. Fagioli. 2013. Monitoring of TNFR1, IL-2Ralpha, HGF, CCL8, IL-8 and IL-12p70 following HSCT and their role as GVHD biomarkers in paediatric patients. Bone Marrow Transplant. 48: 1230-1236. https://doi.org/10.1038/bmt.2013.41
  23. Paczesny, S., O. I. Krijanovski, T. M. Braun, S. W. Choi, S. G. Clouthier, R. Kuick, D. E. Misek, K. R. Cooke, C. L. Kitko, A. Weyand, D. Bickley, D. Jones, J. Whitfield, P. Reddy, J. E. Levine, S. M. Hanash, and J. L. Ferrara. 2009. A biomarker panel for acute graft-versus-host disease. Blood 113: 273-278.
  24. Holcomb, I. N., R. C. Kabakoff, B. Chan, T. W. Baker, A. Gurney, W. Henzel, C. Nelson, H. B. Lowman, B. D. Wright, N. J. Skelton, G. D. Frantz, D. B. Tumas, F. V. Peale, Jr., D. L. Shelton, and C. C. Hebert. 2000. FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO J. 19: 4046-4055. https://doi.org/10.1093/emboj/19.15.4046
  25. Steppan, C. M., S. T. Bailey, S. Bhat, E. J. Brown, R. R. Banerjee, C. M. Wright, H. R. Patel, R. S. Ahima, and M. A. Lazar. 2001. The hormone resistin links obesity to diabetes. Nature 409: 307-312. https://doi.org/10.1038/35053000
  26. Steppan, C. M., J. Wang, E. L. Whiteman, M. J. Birnbaum, and M. A. Lazar. 2005. Activation of SOCS-3 by resistin. Mol. Cell. Biol. 25: 1569-1575. https://doi.org/10.1128/MCB.25.4.1569-1575.2005
  27. Kim, J. Y., W. E. van de, M. Laplante, A. Azzara, M. E. Trujillo, S. M. Hofmann, T. Schraw, J. L. Durand, H. Li, G. Li, L. A. Jelicks, M. F. Mehler, D. Y. Hui, Y. Deshaies, G. I. Shulman, G. J. Schwartz, and P. E. Scherer. 2007. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J. Clin. Invest. 117: 2621-2637. https://doi.org/10.1172/JCI31021
  28. Batista, M. L., Jr., M. Olivan, P. S. Alcantara, R. Sandoval, S. B. Peres, R. X. Neves, R. Silverio, L. F. Maximiano, J. P. Otoch, and M. Seelaender. 2013. Adipose tissue-derived factors as potential biomarkers in cachectic cancer patients. Cytokine 61: 532-539. https://doi.org/10.1016/j.cyto.2012.10.023
  29. Langouche, L., S. V. Perre, S. Thiessen, J. Gunst, G. Hermans, A. D'Hoore, B. Kola, M. Korbonits, and B. G. Van den. 2010. Alterations in adipose tissue during critical illness: An adaptive and protective response? Am. J. Respir. Crit. Care Med. 182: 507-516. https://doi.org/10.1164/rccm.200909-1395OC
  30. Jurcovicova, J., A. Stofkova, M. Skurlova, M. Baculikova, S. Zorad, and M. Stancikova. 2010. Alterations in adipocyte glucose transporter GLUT4 and circulating adiponectin and visfatin in rat adjuvant induced arthritis. Gen. Physiol. Biophys. 29: 79-84. https://doi.org/10.4149/gpb_2010_01_79