are negatively associated with C4D staining, which is a marker for antibody- ... exercise compared with patients without complement fixating DSA. RHC revealed ...
Abstracts S41 8( 7) Donor Specific Antibodies Associated with Micro- and Macrovascular Coronary Disease and Restrictive Myocardial Damage in Heart Transplanted Patients T.S. Clemmensen ,1 P. Koefoed-Nielsen,2 S.H. Poulsen,1 N.R. Holm,1 B.B. Løgstrup,1 E.H. Christiansen,1 L.P. Tolbod,3 H.J. Harms,3 H. Eiskjær.1 1Department of Cardiology, Aarhus University Hospital, Skejby, Denmark, Aarhus N, Denmark; 2Department of Immunology, Aarhus University Hospital, Skejby, Denmark, Aarhus N, Denmark; 3Department of Nuclear Medicine & PET Center, Aarhus University Hospital, Skejby, Denmark, Aarhus N, Denmark.
II. Of the Class II antibodies, 53%, 42.6%, and 4.4% were DR, DQ, and DP respectively. The Class I was predominately against B (54.3%) followed by Cw (28.6%) and A (17.1%). The 1, 2 and 3 year survival after the development of Class I DSA was 91%, 81% and 79% and after Class II DSA was 93%, 80%, and 80%, respectively. Conclusion: At five years, more than a third of CTX patients developed DSA, primarily to Class II. Patients who developed DSA were more than twice as likely to have a PRA > = 20. Once a patient developed DSA their mortality in the subsequent 3 years was approximately 20%. Additional studies are warranted to evaluate long-term survival and graft function.
Purpose: The present study aimed to characterize graft function and hemodynamics at rest and during exercise in stable long-term heart transplanted (HTx) patients with and without donor specific antibodies (DSA). Furthermore, we aimed to evaluate micro and macrovascular function in these patients. Methods: Fifty-seven stable HTx-patients not clinically suspected for antibody-mediated rejection were tested for presence of DSA by Labscreen single antigen bead and Labscreen C1q analysis. The patients underwent echocardiographic graft function assessment during symptom-limited, semisupine exercise test with simultaneous right heart catheterization (RHC). The vasculopathy burden was determined by coronary angiography (CAG), optical coherence tomography (OCT), and perfusion positron emission tomography (PET). Patients were divided into three groups: No DSA, none complement fixating DSA, and C1q positive DSA. Results: Time since transplantation was 9.1±6.2 years. Forty-four patients (77%) had no circulating DSA and thirteen patients (23%) had DSA. DSA were complement fixating in six patients. Patients with complement fixating DSA had significantly reduced longitudinal myocardial deformation measured by global longitudinal strain (GLS) and failed to increase GLS during exercise compared with patients without complement fixating DSA. RHC revealed elevated LV and RV filling pressures in the complement fixating DSA-group. All patients with complement fixating DSA had angiographic signs of cardiac allograft vasculopathy (CAV), and the presence of complement fixating DSA was strongly associated with presence of severe coronary stenosis > 70%, (Odds ratio 20.5 (2.15-195.58), p = 20 (28% v. 12%, p= 0.009) and Class II PRA > = 20 (30% v. 12%, p= 0.006). Median time to the development of Class I DSA was 1151 days and Class II DSA was 1149 days. The 1, 2, 3, 4, and 5 year freedom from any DSA was 95%, 89%, 85%, 76% and 65%. Freedom from the development of Class I and Class II DSA are as in Figure 1. Of those who developed DSA 6 (3%) were to Class 1 alone, 26 (13%) were to Class II alone, and 13 (7%) developed both Class I and
8( 9) Human Leukocyte Antigen-G Polymorphisms Association with Post Heart Transplant Donor Specific Antibodies J. Lazarte ,1 L. Goldraich,2 C. Manlhiot,2 H. Kawajiri,3 A. Ghashghai,1 L. Grosman-Rimon,3 V. Rao,3 D. Delgado.2 1Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2Cardiology, Toronto General Hospital, Toronto, ON, Canada; 3Cardiovascular Surgery, Toronto General Hospital, Toronto, ON, Canada. Purpose: Human Leukocyte Antigen (HLA)-G is a natural immune regulator that inhibits B-lymphocytes’ differentiation, proliferation and antibody secretion. In the context of transplantation, increasing soluble HLA-G levels are negatively associated with C4D staining, which is a marker for antibodymediated rejection. HLA-G expression is regulated by polymorphisms in the gene. Indeed, the association between HLA-G polymorphisms in the recipient and donor and post-transplant donor specific antibodies (DSA) class I has never been explored. DSA can lead to antibody-mediated rejection and are associated with worse outcomes. Objective: to determine the association between HLA-G single nucleotide polymorphisms (SNPs) in the recipient and donor and post-transplant DSA class I. Methods: DNA from adult heart recipients (251) and the corresponding heart donors for (196) recipients, were genotyped for 14bp INDEL, G*01:01, G*01:03, G*01:04, G*01:05N and G*01:06 in the HLA-G gene. Patient sera are routinely assessed for HLA class I antibodies during clinical follow-up. The analysis was performed first in univariable regression models and then in