Detection of citrate synthase-reacting autoantibodies after heart transplantation: an epitope mapping study (original) (raw)
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Transplantation Journal, 2013
Background-Although a link between donor-specific antibodies against human leukocyte antigens type II (DSA II+) and transplant glomerulopathy has been clearly established, its role in cardiac allograft vasculopathy (CAV) is unclear. Methods-DSA were evaluated using solid phase Single Antigen Bead assay before transplant in 51 heart transplant (HTX) recipients. Coronary angiography and three-dimensional intravascular ultrasound (3D IVUS) were performed at baseline and approximately one year after the baseline exam. Results-There were 4 (7.8 %), 11 (21.5%), and 2 (3.9%) patients who had DSA against donor Class I (DSA I+), DSA II+, or both respectively. All patients had negative complement dependent cytotoxic cross match. There was accelerated progression of CAV in the DSA II+ group demonstrated by accelerated progression in plaque index (plaque volume/vessel volume) compared to patients with no DSA II+ antibodies (13.8±12% vs. −7.9±37%; p=0.01). The development of any angiographic CAV was also more common in DSA II+ patients as compared
Cardiac allograft vasculopathy – the cellular attack
Zeitschrift f�r Kardiologie, 2000
Cardiac allograft vasculopathythe cellular attack Summary Studies using genetically manipulated mice show that CD4 T cells and macrophages are important components of the recipient response to transplanted tissues, playing a major role in the development of cardiac allograft vasculopathy (CAV). Under attack, the cells of the graft respond by producing cytokines and growth factors that ultimately lead to Þbroproliferative lesions in the graft vasculature. The progression and severity of these lesions are inßuenced by genetic variation in both donor and recipient.
American Journal of Transplantation, 2004
We studied 361 patients, to evaluate risk factors for cardiac allograft vasculopathy (CAV) onset and severity/diffusion in heart transplantation (HT). Rejection scores (RS) on endomyocardial biopsy were calculated (first year and whole follow-up). CAV onset was defined as any lesion seen at yearly angiography. A CAV severity/diffusion index was calculated for each patient summing up the scores of all lesions. Cox multivariate analysis included: donor age, sex, and weight; recipient sex, age, pre-HT diagnosis, hypertension, diabetes and hyperlipidemia post-HT; number of treated rejections and RS; and immunosuppressive dosage at 3, 6, and 12 months. CAV frequency was 2% at 1 year, 22% at 5 and 39% at 10 years. Risk factors for CAV onset were older donor age [p < 0.0001, relative risk (RR) = = 9.9], male donor (p < 0.001, RR = = 3.2), high RS for severe (≥ 3A) grades (p < 0.02, RR = = 2.01), high cyclosporine at 3 months (p < 0.02, RR = = 1.9). Risk factors for CAV severity/diffusion were higher donor weight (p < 0.01, RR = = 7.5), high prednisone dosage at 1 year (p < 0.0001, RR = = 21.1), and coronary disease pre-HT (p < 0.002, RR = = 9.7). High RS was an independent predictor for CAV onset, not severity/diffusion. This suggests an immune basis for CAV onset and nonimmune modulation for progression. High RS for severe grades may provide a predictor for patients at risk.
Detection of allo- and autoantibodies in kidney transplantation by flow cytometry
Transplantation Proceedings, 1999
A LLOANTIBODIES present in the serum of kidney graft recipients and induced by prior transfusions, transplants, or pregnancies recognize antigens on the graft's surfaces that can lead to graft rejection and loss. 1,2 These alloantibodies may be directed against major histocompatibility antigens or other antigenic systems. 1,2 Recipients may also have autoantibodies whose presence is associated with a better graft acceptance. 1-5 Many techniques have been developed for allo-and autoantibodies detection. The complement-dependent cytotoxicity (CDC) crossmatches are the most commonly used. Among these are the classic NIH, 2,6 Amos, 7 and Antikappa crossmatches 8,9 and the use of DTT for differentiation of IgG and IgM antibodies. 11 The flow cytometry crossmatch (FCXM) is an indirect immunofluorescence test that offers higher reliability and sensitivity. 10 -15 It is controversial whether FCXM has a prognostic value in kidney transplantation. It has been reported that kidney graft recipients with FCXM positive and CDC negative crossmatches have increased rejection episodes and lower graft survival, compared to patients with both FCXM and CDC negative tests. [15][16][17] In high risk groups like retransplanted and multitransfused patients and women with previous pregnancies, the correlation with FCXM is more clear than for low risk patients. 19 -21 Moreover, posttransplant positivization detected by FCXM has also been associated with lower survival rates. 22,23 However, there are also reports showing no association of FCXM positivity and rejection or graft loss. The aim of this study was to evaluate the capacity of FCXM to detect alloantibodies that lead to rejection and graft loss in both cadaveric and living related kidney transplants. Our results show that the alloantibodies detected by flow cytometry are significantly associated with hyperacute and accelerated rejections.
The Challenge of Rejection and Cardiac Allograft Vasculopathy
Heart Failure Reviews - HEART FAIL REV, 2001
Since the first human heart transplantation was performed in 1967, the field of heart transplantation has advanced to the point where survival and acceptable quality of life are commonplace. Despite remarkable progress in the clinical management of rejection, rejection continues to limit survival and quality of life in the heart transplant population. This review will discuss the biologic processes involved in hyperacute rejection, acute rejection, and humoral (vascular) rejection. The development of endomyocardial biopsy techniques represented a significant advancement in the diagnosis of cardiac rejection, and endomyocardial biopsy remains the ‘gold standard’ in the diagnosis of cellular rejection. To date, no noninvasive parameters will diagnose rejection with adequate sensitivity and specificity. Biopsy frequency and immunosuppressive therapies may be tailored to the risk of rejection. Immunosuppression for cardiac transplantation can be divided into three major phases: 1) perio...