The Journal of Heart and Lung Transplantation
Volume 29, Issue 4 , Pages 410-416 , April 2010

Increased erythrocyte C4D is associated with known alloantibody and autoantibody markers of antibody-mediated rejection in human lung transplant recipients

  • Angali Golocheikine, MD

      Affiliations

    • Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
    • ,
  • Dilip S. Nath, MD

      Affiliations

    • Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri
    • ,
  • Haseeb Ilias Basha, MD

      Affiliations

    • Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
    • ,
  • Deepti Saini, PhD

      Affiliations

    • Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
    • ,
  • Donna Phelan, BS

      Affiliations

    • HLA Laboratory, Barnes-Jewish Hospital, St. Louis, Missouri
    • ,
  • Aviva Aloush, RN

      Affiliations

    • Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
    • ,
  • Elbert P. Trulock, MD

      Affiliations

    • Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
    • ,
  • Ramsey R. Hachem, MD

      Affiliations

    • Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
    • ,
  • G. Alexander Patterson, MD

      Affiliations

    • Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri
    • ,
  • Joseph M. Ahearn, MD

      Affiliations

    • Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
    • ,
  • Thalachallour Mohanakumar, PhD

      Affiliations

    • Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
    • Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri
    • Corresponding Author InformationReprint requests: T. Mohanakumar, PhD, Washington University School of Medicine, Department of Surgery, Box 8109-3328 CSRB, 660 S Euclid Ave, St. Louis, MO 63110. Telephone: 314-362-8463. Fax: 314-747-1560

References 

  1. Terasaki PI. Humoral theory of transplantation. Am J Transplant. 2003;3:665–673
  2. Masson E, Stern M, Chabod J, et al. Hyperacute rejection after lung transplantation caused by undetected low-titer anti-HLA antibodies. J Heart Lung Transplant. 2007;26:642–645
  3. Sundaresan S, Mohanakumar T, Smith MA, et al. HLA-A locus mismatches and development of antibodies to HLA after lung transplantation correlate with the development of bronchiolitis obliterans syndrome. Transplantation. 1998;65:648–653
  4. Girnita AL, McCurry KR, Iacono AT, et al. HLA-specific antibodies are associated with high-grade and persistent-recurrent lung allograft acute rejection. J Heart Lung Transplant. 2004;23:1135–1141
  5. Girnita AL, Duquesnoy R, Yousem SA, et al. HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction. Am J Transplant. 2005;5:131–138
  6. Collins AB, Schneeberger EE, Pascual MA, et al. Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries. J Am Soc Nephrol. 1999;10:2208–2214
  7. Feucht HE, Schneeberger H, Hillebrand G, et al. Capillary deposition of C4d complement fragment and early renal graft loss. Kidney Int. 1993;43:1333–1338
  8. Feucht HE. Complement C4d in graft capillaries—the missing link in the recognition of humoral alloreactivity. Am J Transplant. 2003;3:646–652
  9. Stewart S, Fishbein MC, Snell GI, et al. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant. 2007;26:1229–1242
  10. Fukami N, Ramachandran S, Saini D, et al. Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of chronic rejection. J Immunol. 2009;182:309–318
  11. Bharat A, Fields RC, Trulock EP, Patterson GA, Mohanakumar T. Induction of IL-10 suppressors in lung transplant patients by CD4+25+ regulatory T cells through CTLA-4 signaling. J Immunol. 2006;177:5631–5638
  12. Goers TA, Ramachandran S, Aloush A, Trulock E, Patterson GA, Mohanakumar T. De novo production of K-alpha1 tubulin-specific antibodies: role in chronic lung allograft rejection. J Immunol. 2008;180:4487–4494
  13. Jaramillo A, Smith MA, Phelan D, et al. Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation. Transplantation. 1999;67:1155–1161
  14. Manzi S, Navratil JS, Ruffing MJ, et al. Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus. Arthritis Rheum. 2004;50:3596–3604
  15. Lee KC, Chang CY, Chuang YC, et al. Measurement of human erythrocyte C4d to erythrocyte complement receptor 1 ratio in cardiac transplant recipients with acute symptomatic allograft failure. Transplant Proc. 2008;40:2638–2642
  16. Iwata T, Philipovskiy A, Fisher AJ, et al. Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction. J Immunol. 2008;181:5738–5747
  17. Westall GP, Snell GI, McLean C, Kotsimbos T, Williams T, Magro C. C3d and C4d deposition early after lung transplantation. J Heart Lung Transplant. 2008;27:722–728
  18. Woo MS. Overview of lung transplantation. Clin Rev Allergy Immunol. 2008;35:154–163
  19. Orens JB, Garrity ER. General overview of lung transplantation and review of organ allocation. Proc Am Thorac Soc. 2009;6:13–19
  20. Ng CY, Madsen JC, Rosengard BR, Allan JS. Immunosuppression for lung transplantation. Front Biosci. 2009;14:1627–1641
  21. Allan JS. Immunosuppression for lung transplantation. Semin Thorac Cardiovasc Surg. 2004;16:333–341
  22. Reinsmoen NL, Bolman RM, Savik K, Butters K, Hertz MI. Are multiple immunopathogenetic events occurring during the development of obliterative bronchiolitis and acute rejection?. Transplantation. 1993;55:1040–1044
  23. Schulman LL, Ho EK, Reed EF, et al. Immunologic monitoring in lung allograft recipients. Transplantation. 1996;61:252–257
  24. Scornik JC, Zander DS, Baz MA, Donnelly WH, Staples ED. Susceptibility of lung transplants to preformed donor-specific HLA antibodies as detected by flow cytometry. Transplantation. 1999;68:1542–1546
  25. Takemoto SK, Zeevi A, Feng S, et al. National conference to assess antibody-mediated rejection in solid organ transplantation. Am J Transplant. 2004;4:1033–1041
  26. Diujvestijn AM, Derhaag JG, van Breda Vriesman PJ. Complement activation by anti-endothelial cell antibodies in MHC-mismatched and MHC-matched heart allograft rejection: anti-MHC-, but not anti non-MHC alloantibodies are effective in complement activation. Transpl Int. 2000;13:363–371
  27. Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV. Genotypic variation in the transforming growth factor-beta 1 gene: association with transforming growth factor beta 1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation. 1998;66:1014–1020
  28. Morrell MR, Patterson GA, Trulock EP, Hachem RR. Acute antibody-mediated rejection after lung transplantation. J Heart Lung Transplant. 2009;28:96–100
  29. Magro CM, Pope Harman A, Klinger D, et al. Use of C4d as a diagnostic adjunct in lung allograft biopsies. Am J Transplant. 2003;3:1143–1154
  30. Wallace WD, Reed EF, Ross D, Lassman CR, Fishbein MC. C4d staining of pulmonary allograft biopsies: an immunoperoxidase study. J Heart Lung Transplant. 2005;24:1565–1570

PII: S1053-2498(09)00798-0

doi: 10.1016/j.healun.2009.10.003

The Journal of Heart and Lung Transplantation
Volume 29, Issue 4 , Pages 410-416 , April 2010

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