C4d staining in humoral rejection of cardiac allografts
Julius M. CruseJeanann L. SuggsRobert E. LewisJoshua GoodinBret C. AllenSteven A. BiglerCharles K. MooreRegina ThompsonHolly McIntire
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Abstract:
C4d “staining” of interstitial capillaries of endomyocardial biopsies serves as an indicator of a humoral component of cardiac allograft rejection. In the present study, two cardiac allograft recipients were monitored serially for both cellular and humoral rejection. Cellular rejection, evaluated by light microscopy, and humoral rejection, judged by C4d immunofluorescent “staining”, were treated with appropriate immunosuppressants. Weekly serial biopsies of the first patient for nine weeks revealed grade 1A to 1B moderate cellular rejection. Humoral rejection peaked at 3+ “staining” for C4d after one week transplant, and then wavered between 2+ (moderate “staining”) to 1+ (weak”staining”) Biopsies of the second patient revealed maximal humoral rejection (3+) after one week but diminished to 2+ thereafter. Cellular rejection was graded as 3A after three weeks but declined steadily to negligible cellular rejection through week 15. Whereas, cellular rejection peaked at 14 – 21 days, humoral rejection was greatest in the early post transplant period. Results revealed the significance not only of traditional light microscopy in evaluating the severity of cellular rejection in endomyocardial biopsies of cardiac allotransplants, but also the value of C4d immunofluorescent “staining” of interstitial capillaries as an indicator of humoral rejection episodes, which may require modified therapy.Keywords:
Endomyocardial Biopsy
Humoral immunity
Positive staining
Transplant rejection
Immunosuppression
Endomyocardial Biopsy
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In 15 patients after orthotopic transplantation of the heart the authors made repeated examinations of electromaps of the R wave and endomyocardial biopsies (TMB) during a long-term, at least one-year, investigation. In the detection of rejection EMB plays a dominating role. In three patients the authors found at the time of rejection a significant reduction of the R waves on maps, which correlated closely with the bioptic findings. It was revealed that maps of R waves are a good indicator of rejection of the transplanted heart. The examination may prove helpful when checking treatment of rejection but does not lead so far to a restriction of the number of endomyocardial biopsies of the heart.
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Graft rejection
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Among patients undergoing heart transplantation, a fundamental clinical concern is the risk of rejection of the new organ. Although modern immunosuppressive regimens have reduced the incidence of rejection substantially, about one quarter of recipients will still have a rejection episode requiring treatment during the first year after transplantation.1 Acute rejection is the cause of 12% of deaths occurring between 1 month and 1 year after transplantation.1 There is no established noninvasive marker of rejection available for heart-transplant recipients; instead they must undergo serial endomyocardial biopsies with histologic evaluation of myocardial tissue to monitor for rejection. Endomyocardial biopsy is an invasive . . .
Endomyocardial Biopsy
Graft rejection
Heart transplants
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The purpose of this study was to investigate the frequency and prognostic importance of acute cellular rejection after heart transplant.All 84 heart transplant patients at our center from January 1993 to January 2014, including all 576 endomyocardial biopsies, were evaluated with retrospective review of clinical records and endomyocardial biopsies. Routine and clinically indicated endomyocardial biopsies after heart transplant were graded for acute cellular rejection (2005 International Society for Heart and Lung Transplantation Working Formulation). Survival analysis was performed using Kaplan-Meier method.There were 61 male (73%) and 23 female recipients. Median age at heart transplant was 29 years (range, 1-62 y). Posttransplant early mortality rate was 17.9% (15 patients). In the other 69 patients, 23 patients died and 46 patients (66.7%) were alive at mean 69.3 ± 7.2 months after heart transplant. Mean follow-up was 35.4 ± 29.8 months (range, 0.07-117.5 mo). Mean 8.4 ± 4.2 endomyocardial biopsies (range, 1-19 biopsies) were performed per patient. Median first biopsy time was 7 days (range, 1-78 d). The frequency of posttransplant acute cellular rejection was 63.8% (44 of 69 patients) by histopathology; 86% patients experienced the first episode of acute cellular rejection within 6 months after transplant. There were 18 patients with acute cellular rejection ≥ grade 2R on ≥ 1 endomyocardial biopsy in 44 patients with acute cellular rejection. No significant difference was observed between survival rates of patients with grade 1R or ≥ grade 2R acute cellular rejection, or between survival rates of patients with or without diagnosis of any grade of acute cellular rejection. Acute cellular rejection was not related to any prognostic risk factor.Acute cellular rejection had no negative effect on heart recipient long-term survival, but it was a frequent complication after heart transplant, especially within the first 6 months.
Endomyocardial Biopsy
Single Center
Histopathology
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The author reconsiders Stanford classification which separates 3 degrees of rejection of transplanted hearts: minimal, moderate or severe rejection. This classification, widely used, was enriched with J. Kennitz's sub-varieties, based on more than 4,000 endomyocardial biopsies, performed on 132 patients who underwent heart transplantation. Interpretation of the histopathologic results of endomyocardial biopsies requires careful knowledge of simultaneous clinical or biochemical data. However, heart biopsy remains indispensible since it is the only test providing information on the presence or absence of cellular infiltrate and on myocardial fibers changes. The difficulties result from the very small size of all samples. Several types of rejection are illustrated and commented. However, the author's experience is presently restricted and hardly allows separating moderate rejections from minimal or severe rejections.
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Graft rejection
Human heart
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