Pre-transplant soluble CD30 (sCD30) for the prediction of acute cellular rejection in heart transplant recipients. Orlova O.V.1, Bugrov A.V.1, Shevchenko A.О.2, Kazakov E.N.1, Kormer A.J.1, Iljinsky I.M.1, Shevchenko О.P.1 1-Federal V. Shumakov Research Center of Transplantology and Artificial Organs, Moscow, Russia 2-Russian State Medical University, Moscow, Russia Introduction Results Despite the use of potent immunosuppressive agents, acute cellular rejection (ACR) affects early morbidity and mortality after heart transplantation (HTx). CD30, a cell surface glycoprotein, is a member of the tumor necrosis factor receptor superfamily. Pre- or post-transplant elevated levels of soluble form of CD30 (sCD30) have been shown to be associated with an impaired outcome in renal transplant recipients. A positive correlation was found between sCD30 and soluble Fas (sFas) levels in heart transplant recipients (Fig.2.). r=0,35, p=0,034 Objectives We have evaluated the pre-transplant plasma level of sCD30 with the aim of determining its value in predicting ACR in heart transplant recipients. Methods 75 heart transplant recipients, 70 men and 5 women, aged 44.5±9.5 (18-65) years were followed for 36 months after the operation performed for dilated (41 patients) or ischemic (34 patients) cardiomyopathy. Immunosuppressive therapy included steroids, cyclosporine (or tacrolimus), and mycophenolate mofetil. The diagnosis of acute cellular allograft rejection was made by endomyocardial biopsy performed either routinely or because of suggestive symptoms. Plasma levels of sCD30 were measured by ELISA. Fig.2. Correlation between sCD30 and sFas plasma levels in heart transplant recipients The difference in sCD30 among patients initially presented with dilated or ischemic cardiomyopathy was insignificant as well (6.7±3.1 IU/ml vs 7.1±3.5 IU/ml, respectively, p>0.05). During follow-up major study event defined as ACR grade 2R or more (ISHLT, 2004) occurred in 7 (38.9%) recipients with pre-transplant sCD30 levels above median (>8 IU/ml) and only in 1 (1.75%) patient with low sCD30 (<8 IU/ml). Patients with high pre-transplant sCD30 levels had >5-fold higher risk for ACR than patients with low sCD30 levels (relative risk, RR 5.3; 95% confidence interval 1.4 to 9.1). Event-free survival analysis showed significant difference in outcomes among patients with elevated and low levels of pre-transplant sCD30 (p<0.05) (Fig.3.). Results sCD30 plasma levels increased after HTx and were significantly higher in heart recipients (13.7±6.2 IU/ml) than in patients before HTx (6.9±3.4 IU/ml). Among heart transplant recipients sCD30 plasma levels were higher in patients with acute rejection (17.2±6.9 IU/ml) than in those without ACR (10.8±4.6 IU/ml) (Fig.1.). p<0.01 sCD30, IU/ml 13.7+6.2* 5 before HTx 6.9+3.4 10 15 A sCD30, IU/ml 17.2+6.9* 5 ACR grade 0 or 1R ACR grade 2R or > 10.8+4.6 10 p<0.01 15 B sCD30>8 IU\ml sCD30<8 IU\ml after HTx Fig.1. Increased sCD30 plasma levels in patients after heart transplantation (A) and in recipients with acute rejection (B). p = ,00001 There was no significant correlation for sCD30 with age, gender, or plasma levels of C-reactive protein, interleukin-6, neopterin, homocysteine, cardiolipin autoantibodies (aCL), pregnancy-associated plasma protein A (PAPP-A), placenta growth factor (PlGF) (Table). Fig.3. Pre-transplant sCD30 is a potential biomarker of a raised risk of early development of ACR after HTx Table. Association between sCD30 and parameters in heart transplant recipients Conclusions Measurement of pre-transplant sCD30 plasma levels might offer a tool to recognize patients at high risk of acute cellular rejection after HTx. Parameters r value p value age 0.098 0.724 total cholesterol, mmol/l 0.131 0.567 LDL-C, mmol/l 0.128 0.648 HLD-C, mmol/l 0.182 0.679 triglyceride, mmol/l 0.093 0.842 hsCRP, mg/l 0.135 IL-6, pg/ml 0.308 0.091 neopterin, nmol/l 0.089 0.124 homocysteine, μmol/l 0.255 0.189 aCL antibodies, IU/ml 0.197 0.092 PAPP-A, mlU/l 0.304 0.075 PlGF, pg/ml 0.298 0.087 References Heinemann F, Rebmann V, Witzke O. et al. Association of elevated pretransplant sCD30 levels with graft loss in 206 patients treated with modern immunosupressive therapies after renal transplantation. Clin Transplant 2007 Kamali K, Abbasi MA, Farokhi B. et al. Posttransplant soluble CD30 as a predictor of acute renal allograft rejection. Exp Clin Transplant 2009 Spiridon C, Hunt J, Mack M. et al. Evaluation of soluble CD30 as an immunologic marker in heart transplant recipients. Transplant Proc 2006 Stehlik J, Edwards LB, Kucheryavaya AY. et al. The Registry of the International Society for Heart and Lung Transplantation: Twenty-seventh official adult heart transplant report-2010. The J Heart and Lung Transplantation 2010 Presented at the 15th Congress of the European Society for Organ Transplantation, 4-7 September 2011, Glasgow, Scotland