Abstract
Purpose
The existence of platelet-derived growth factor (PDGF) receptor autoantibodies in systemic sclerosis is conflicting, and such antibodies were also detected in patients with chronic graft-versus-host disease (GvHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). We therefore aimed to screen for PDGF receptor autoantibodies in patients with chronic GvHD.
Patients and methods
We evaluated the existence of PDGF receptor autoantibodies in 39 patients, while 17 patients presented with a limited and 8 patients with an extensive chronic GvHD, respectively. Furthermore, 14 out of 39 patients had no chronic GvHD.
Results
We detected at least low levels of PDGF receptor autoantibodies in nearly all (35 of 39) patients after allogeneic PBSCT. Interestingly, only one of six patients with high levels of PDGF receptor autoantibodies presented with an extensive chronic GvHD, while the remaining six patients had no clinical signs of chronic GvHD. Thus, there was no correlation between the quantitative detection of antibodies directed against the PDGF receptor and the presence or severity of chronic GvHD.
Conclusion
Platelet-derived growth factor receptor autoantibodies could easily be detected in patient sera. Nevertheless, we did not observe any correlation between the presence of PDGF receptor autoantibodies and the severity of chronic GvHD in patients who underwent allogeneic PBSCT.
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References
Atkinson K, Horowitz MM, Gale RP, Lee MB, Rimm AA, Bortin MM (1989) Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease. Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant 4:247–254
Ball LM, Egeler RM (2008) Acute GvHD: pathogenesis and classification. Bone Marrow Transplant 41(Suppl 2):S58–S64
Baroni SS, Santillo M, Bevilacqua F, Luchetti M, Spadoni T, Mancini M, Fraticelli P, Sambo P, Funaro A, Kazlauskas A, Avvedimento EV, Gabrielli A (2006) Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 354:2667–2676
Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R, Kashyap A, Flowers ME, Lilleby K, Chauncey TR, Storb R, Appelbaum FR (2001) Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 344:175–181
Bjorklund A, Aschan J, Labopin M, Remberger M, Ringden O, Winiarski J, Ljungman P (2007) Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation. Bone Marrow Transplant 40:1055–1062
Chakraverty R, Mackinnon S (2011) Allogeneic transplantation for lymphoma. J Clin Oncol official J Am Soc ClinOncol 29:1855–1863
Choi SW, Levine JE, Ferrara JL (2010) Pathogenesis and management of graft-versus-host disease. Immunol Allergy Clin North Am 30:75–101
Chu YW, Gress RE (2008) Murine models of chronic graft-versus-host disease: insights and unresolved issues. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 14:365–378
Classen JF, Henrohn D, Rorsman F, Lennartsson J, Lauwerys BR, Wikstrom G, Rorsman C, Lenglez S, Franck-Larsson K, Tomasi JP, Kampe O, Vanthuyne M, Houssiau FA, Demoulin JB (2009) Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis. Arthritis Rheum 60:1137–1144
Couriel DR, Saliba RM, Giralt S, Khouri I, Andersson B, de Lima M, Hosing C, Anderlini P, Donato M, Cleary K, Gajewski J, Neumann J, Ippoliti C, Rondon G, Cohen A, Champlin R (2004) Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 10:178–185
Daniels CE, Wilkes MC, Edens M, Kottom TJ, Murphy SJ, Limper AH, Leof EB (2004) Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. J Clin Investig 114:1308–1316
Ferrara JL, Reddy P (2006) Pathophysiology of graft-versus-host disease. Semin Hematol 43:3–10
Ferrara JL, Levine JE, Reddy P, Holler E (2009) Graft-versus-host disease. Lancet 373:1550–1561
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME (2005) National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 11:945–956
Flowers ME, Parker PM, Johnston LJ, Matos AV, Storer B, Bensinger WI, Storb R, Appelbaum FR, Forman SJ, Blume KG, Martin PJ (2002) Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood 100:415–419
George B, Pati N, Gilroy N, Ratnamohan M, Huang G, Kerridge I, Hertzberg M, Gottlieb D, Bradstock K (2010) Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis official J Transplant Soc 12:322–329
Jagasia MH, Savani BN, Stricklin G, Engelhardt B, Kassim A, Dixon S, Chen H, Chinratanalab W, Goodman S, Greer JP, Schuening F (2009) Classic and overlap chronic graft-versus-host disease (cGVHD) is associated with superior outcome after extracorporeal photopheresis (ECP). Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 15:1288–1295
Kier P, Penner E, Bakos S, Kalhs P, Lechner K, Volc-Platzer B, Wesierska-Gadek J, Sauermann G, Gadner H, Emminger-Schmidmeier W et al (1990) Autoantibodies in chronic GVHD: high prevalence of antinucleolar antibodies. Bone Marrow Transplant 6:93–96
Leder C, Ortler S, Seggewiss R, Einsele H, Wiendl H (2007) Modulation of T-effector function by imatinib at the level of cytokine secretion. Exp Hematol 35:1266–1271
Lister J, Messner H, Keystone E, Miller R, Fritzler MJ (1987) Autoantibody analysis of patients with graft versus host disease. J Clin Lab Immunol 24:19–23
Loizos N, Lariccia L, Weiner J, Griffith H, Boin F, Hummers L, Wigley F, Kussie P (2009) Lack of detection of agonist activity by antibodies to platelet-derived growth factor receptor alpha in a subset of normal and systemic sclerosis patient sera. Arthritis Rheum 60:1145–1151
Magro L, Mohty M, Catteau B, Coiteux V, Chevallier P, Terriou L, Jouet JP, Yakoub-Agha I (2009) Imatinib mesylate as salvage therapy for refractory sclerotic chronic graft-versus-host disease. Blood 114:719–722
Markova B, Herrlich P, Ronnstrand L, Bohmer FD (2003) Identification of protein tyrosine phosphatases associating with the PDGF receptor. Biochemistry 42:2691–2699
Mielcarek M, Martin PJ, Leisenring W, Flowers ME, Maloney DG, Sandmaier BM, Maris MB, Storb R (2003) Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 102:756–762
Olivieri A, Locatelli F, Zecca M, Sanna A, Cimminiello M, Raimondi R, Gini G, Mordini N, Balduzzi A, Leoni P, Gabrielli A, Bacigalupo A (2009) Imatinib for refractory chronic graft-versus-host disease with fibrotic features. Blood 114:709–718
Osumi T, Miharu M, Tanaka R, Du W, Takahashi T, Shimada H (2012) Imatinib is effective for prevention and improvement of fibrotic fasciitis as a manifestation of chronic GVHD. Bone Marrow Transplant 47:139–140
Pidala J, Kurland B, Chai X, Majhail N, Weisdorf DJ, Pavletic S, Cutler C, Jacobsohn D, Palmer J, Arai S, Jagasia M, Lee SJ (2011) Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium. Blood 117:4651–4657
Remberger M, Ackefors M, Berglund S, Blennow O, Dahllof G, Dlugosz A, Garming-Legert K, Gertow J, Gustafsson B, Hassan M, Hassan Z, Hauzenberger D, Hagglund H, Karlsson H, Klingspor L, Kumlien G, Le Blanc K, Ljungman P, Machaczka M, Malmberg KJ, Marschall HU, Mattsson J, Olsson R, Omazic B, Sairafi D, Schaffer M, Svahn BM, Svenberg P, Swartling L, Szakos A, Uhlin M, Uzunel M, Watz E, Wernerson A, Wikman A, Wikstrom AC, Winiarski J, Ringden O (2011) Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. A single-center study. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 17:1688–1697
Rowe JM (2011) Interpreting data on transplant selection and outcome in adult acute lymphoblastic leukemia (ALL). Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 17:S76–S83
Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R (1998) Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91:756–763
Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S, Erickson K, Flowers M, Hansen J, Loughran T et al (1991) Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 28:250–259
Svegliati S, Olivieri A, Campelli N, Luchetti M, Poloni A, Trappolini S, Moroncini G, Bacigalupo A, Leoni P, Avvedimento EV, Gabrielli A (2007) Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood 110:237–241
Wolff D, Schleuning M, von Harsdorf S, Bacher U, Gerbitz A, Stadler M, Ayuk F, Kiani A, Schwerdtfeger R, Vogelsang GB, Kobbe G, Gramatzki M, Lawitschka A, Mohty M, Pavletic SZ, Greinix H, Holler E (2011) Consensus conference on clinical practice in chronic GVHD: second-line treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 17:1–17
Zerr P, Distler A, Palumbo-Zerr K, Tomcik M, Vollath S, Dees C, Egberts F, Tinazzi I, Del Galdo F, Distler O, Schett G, Spriewald BM, Distler JH (2012) Combined inhibition of c-Abl and PDGF receptors for prevention and treatment of murine sclerodermatous chronic graft-versus-host disease. Am J Pathol 181:1672–1680
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This work was supported by a grant from the Deutsche Krebshilfe foundation (Az. 108868).
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Herbert G. Sayer and Sebastian Scholl contributed equally to this work.
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Spies-Weisshart, B., Schilling, K., Böhmer, F. et al. Lack of association of platelet-derived growth factor (PDGF) receptor autoantibodies and severity of chronic graft-versus-host disease (GvHD). J Cancer Res Clin Oncol 139, 1397–1404 (2013). https://doi.org/10.1007/s00432-013-1451-z
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DOI: https://doi.org/10.1007/s00432-013-1451-z