11th banff conference lung transplant pathology
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Summary presentation by Carol F. Farver, MD and W. Dean Wallace, MD, Co-Chairs, 11th Banff Conference-Lung, Paris, France June 2011.
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11th banff conference lung transplant pathology
- 1. 11 th Banff Conference on Allograft Pathology Carol F. Farver, MD Cleveland Clinic W. Dean Wallace, MD UCLA Co-Chairs, 11 th Banff Conference-Lung June 2011
- 4. CLINICAL FEATURES OF AMR IN LUNG TRANSPLANTATION Ramsey Hachem, MD June 7, 2011
- 10. b Capillaries injury with pneumonitis: n=9
- 11. +C4d staining: n=19
- 13. DSA clearance Persistent DSA Cleared DSA log rank p = 0.005
- 15. Overall Survival (n=19 patients) 10/19 (53%) died AMR, n = 5 BOS, n = 4 Pneumonia, n = 1
- 18. Immunology of AMR in Lung Transplantation 11 th Banff Conference | June 7, 2011 Medhat Askar, MD, PhD Director, Allogen Laboratories, Cleveland Clinic Associate Professor, Department of Surgery Cleveland Clinic Lerner College of Medicine at Case Western Reserve University School of Medicine
- 21. RESULTS Positive Pre-Tx DSA Reference Group P Value ACR (≥ ISHLT grade II) 43% 29% 0.0009 ACR/100 Pt./Yr 20.6 7.7
- 23. Pos C4d
- 24. Pos C4d
- 25. Pos C4d
- 29. W. Dean Wallace, M.D. Associate Professor of Pathology David Geffen School of Medicine UCLA Medical Center Pathology of Antibody-Mediated Rejection of the Lung Allograft
- 33. Post capillary venule Nonspecific background staining Nonspecific C4d staining
- 34. Nonspecific C4d staining Nonspecific elastic staining Hyaline membranes in DAD
- 35. Capillaritis in transplant patient with acute pneumonia
- 38. Putative Stages of Humoral Response to an Organ Graft – 2003 NIH recommendations I: Latent humoral response/Silent humoral reaction Circulating antibody alone (without biopsy findings or graft dysfunction) III: Sub-clinical humoral rejection Circulating antibody, (without graft dysfunction) IV: Humoral rejection Circulating antibody, graft dysfunction tissue pathology tissue pathology,
- 39. I: Latent humoral response/Silent humoral reaction/Sub-clinical humoral rejection Circulating antibody alone (without biopsy findings or graft dysfunction) II: Humoral rejection Circulating antibody, graft dysfunction Where is the pathologist?
- 44. C4d
- 45. C4d does not correlate with pathology
- 46. Pathology does correlate with DSA
- 47. Pathology is associated with lung allograft survival
- 48. Pathology + DSA is associated with lung allograft survival
- 49. Suspected AMR (Pathology + DSA + dysfunction) is associated with lung allograft survival
- 57. The journey of a thousand miles begins with a single step…… Lao-tzu, Chinese philosopher 604 BC - 531 BC
Editor's Notes
- Traditionally, lung rejection has been regarded as a T-cell mediated process And standard immunosuppression targeting T-cell proliferation and function has improved graft survival and made transplantation a clinical reality But a potential role for antibodies in rejection has long been suspected since HLA antibodies are detected in patients with rejection HLA antibodies are known to cause different syndromes of rejection after kidney transplantation And HLA antibodies are associated with acute cellular rejection and BOS after lung transplantation But AMR remains enigmatic after LTX
- The association between the development of HLA antibodies and BOS was recognized in the late 90s The development of AB preceded the diagnosis of BOS by an average of 20 months Multiple centers corroborated these findings and AB to both class I and class II molecules were associated with BOS These findings underscore the role of humoral immunity in graft rejection after lung transplantation
- The purpose of this study is to review a series of cases of AMR from our center and describe the clinicopathological findings
- All patients had circulating DSA detected at the time of diagnosis The DSA was to Class I only in 2 of 19; to Class II only in 13 of 19; and to Class I and II in 4 of 19 DSA mean MFI 5841; range: 975-14232
- Pneumonitis with fibrin deposition and diffuse alveolar damage Neutrophilic interstitial infiltration Alveolar hemorrhage
- Neutrophils in alveolar septa
- Focal capillary endothelial C4d deposition
- Overall, 9 of the 12 patients with persistent DSA died compared to 1 of the 7 patients who cleared the DSA
- Overall, 10 of the 19 patients have died 5 died acutely of refractory AMR 4 of BOS 1 of pneumonia
- AMR may be the cause of acute graft failure But a high index of suspicion is necessary for the diagnosis Less severe cases may not result in clinical graft dysfunction similar to most cases of acute cellular rejection & may be unrecognized Yet, these cases may have an impact on BOS development