Effect of development of antibodies to hla and cytomegalovirus mismatch on lung transplantation survival and development of bronchiolitis obliterans syndrome,☆☆,,★★,,♢♢

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Abstract

Objective: A retrospective analysis was performed to examine the role of HLA antibodies and cytomegalovirus mismatch on the development of bronchiolitis obliterans syndrome and survival after lung transplantation. Methods: Of 339 consecutive lung transplantations performed over a 102-month interval, 301 patients survived at least 3 months. There was a minimum follow-up period of 13 months. Bronchiolitis obliterans syndrome was defined as a decline in forced expiratory volume in 1 second less than 80% of posttransplantation baseline and/or histologic presence of obliterative bronchiolitis and was defined as occurring “early” if documented within 3 years of transplantation. Variables analyzed included preoperative donor and recipient cytomegalovirus status and the development of antibodies to human leukocyte antigens after transplantation. Microcytotoxicity was used to determine the presence of antibodies to human leukocyte antigens. Variables were subjected to Kaplan-Meier analysis to determine their impact on freedom from bronchiolitis obliterans syndrome and survival. Results: The development of antibodies to human leukocyte antigens after transplantation correlated significantly with bronchiolitis obliterans syndrome (P = .02). The development of antibodies to human leukocyte antigens did not affect survival (P = .33) unless they were detected within 2 years of transplantation (P = .04). There was greater frequency of early bronchiolitis obliterans syndrome in cytomegalovirus seronegative patients who received allografts from seropositive donors compared with all other combinations (P = .02). There was also a trend toward worse survival of cytomegalovirus seronegative patients who received allografts from seropositive donors (P = .13). Conclusion: These data suggest that bronchiolitis obliterans syndrome is the result of an immune-mediated process in which HLA antibodies and cytomegalovirus may play a significant role. (J Thorac Cardiovasc Surg 1998;116:812-20)

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From the Divisions of Cardiothoracic Surgerya and Transplantation,b Department of Surgery; Division of Pulmonary and Critical Care Medicine, Department of Medicinec; and the HLA Laboratoryd; Barnes-Jewish Hospital, Washington University School of Medicine, St Louis.

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This work supported in part by NIH grant HL56643.

M.A.S. is a US Public Health Service National Research Service Award recipient.

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Read at the Seventy-eighth Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass, May 3-6, 1998.

Address for reprints: Sudhir Sundaresan, MD, Washington University School of Medicine, Division of Cardiothoracic Surgery, Suite 3108, Queeny Tower, One Barnes Hospital Plaza, St Louis, MO 63110.

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