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Immunology in Lung Transplantation

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Lung Transplantation

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Abstract

Immunology plays an expanded role in lung transplantation compared to transplantation of other vascularized allografts, specifically the contribution of innate immunity. The lung is in constant contact with the external environment, contending with exposure to pathogens and irritants. Specialized tissues in addition to innate and adaptive immune responses have evolved to protect the lung from these external threats; these systems must continue to function in the lung allograft. After lung transplantation, mismatched HLA antigens are the most common target of the adaptive immune system. In addition, other proteins normally not available to the immune system but exposed after tissue damage can stimulate antibody responses and contribute to allograft destruction. Immunosuppressive therapy does not discriminate between allogenic responses and those required to fight external pathogens. Precision medicine including laboratory testing to identify the targets of the alloimmune response is needed to tailor therapy for each recipient.

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References

  1. Whitsett JA, Alenghat T. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nat Immunol. 2015;16(1):27–35.

    Article  PubMed  CAS  Google Scholar 

  2. Kopf M, Schneider C, Nobs SP. The development and function of lung-resident macrophages and dendritic cells. Nat Immunol. 2015;16(1):36–44.

    Article  PubMed  CAS  Google Scholar 

  3. Hussell T, Bell TJ. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol. 2014;14(2):81–93.

    Article  PubMed  CAS  Google Scholar 

  4. Cauley LS, Lefrancois L. Guarding the perimeter: protection of the mucosa by tissue-resident memory T cells. Mucosal Immunol. 2013;6(1):14–23.

    Article  PubMed  CAS  Google Scholar 

  5. Chiu C, Openshaw PJ. Antiviral B cell and T cell immunity in the lungs. Nat Immunol. 2015;16(1):18–26.

    Article  PubMed  CAS  Google Scholar 

  6. Rangel-Moreno J, Hartson L, Navarro C, Gaxiola M, Selman M, Randall TD. Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis. J Clin Invest. 2006;116(12):3183–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Moyron-Quiroz JE, Rangel-Moreno J, Kusser K, Hartson L, Sprague F, Goodrich S, et al. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat Med. 2004;10(9):927–34.

    Article  PubMed  CAS  Google Scholar 

  8. Foo SY, Phipps S. Regulation of inducible BALT formation and contribution to immunity and pathology. Mucosal Immunol. 2010;3(6):537–44.

    Article  PubMed  CAS  Google Scholar 

  9. Aurora P, Boucek MM, Christie J, Dobbels F, Edwards LB, Keck BM, et al. Registry of the International Society for Heart and Lung Transplantation: tenth official pediatric lung and heart/lung transplantation report--2007. J Heart Lung Transplant. 2007;26(12):1223–8.

    Article  PubMed  Google Scholar 

  10. Kim IK, Bedi DS, Denecke C, Ge X, Tullius SG. Impact of innate and adaptive immunity on rejection and tolerance. Transplantation. 2008;86(7):889–94.

    Article  PubMed  CAS  Google Scholar 

  11. Wood KJ, Goto R. Mechanisms of rejection: current perspectives. Transplantation. 2012;93(1):1–10.

    Article  PubMed  Google Scholar 

  12. Neefjes J, Jongsma ML, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol. 2011;11(12):823–36.

    Article  PubMed  CAS  Google Scholar 

  13. Afzali B, Lombardi G, Lechler RI. Pathways of major histocompatibility complex allorecognition. Curr Opin Organ Transplant. 2008;13(4):438–44.

    Article  PubMed  Google Scholar 

  14. Palmer MT, Weaver CT. Autoimmunity: increasing suspects in the CD4+ T cell lineup. Nat Immunol. 2010;11(1):36–40.

    Article  PubMed  CAS  Google Scholar 

  15. Vukmanovic-Stejic M, Vyas B, Gorak-Stolinska P, Noble A, Kemeny DM. Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell surface and functional phenotypes. Blood. 2000;95(1):231–40.

    PubMed  CAS  Google Scholar 

  16. Strom TB, Koulmanda M. Recently discovered T cell subsets cannot keep their commitments. J Am Soc Nephrol. 2009;20(8):1677–80.

    Article  PubMed  CAS  Google Scholar 

  17. Hanidziar D, Koulmanda M. Inflammation and the balance of Treg and Th17 cells in transplant rejection and tolerance. Curr Opin Organ Transplant. 2010;15(4):411–5.

    Article  PubMed  Google Scholar 

  18. Hall DJ, Baz M, Daniels MJ, Staples ED, Klodell CT, Moldawer LL, et al. Immediate postoperative inflammatory response predicts long-term outcome in lung-transplant recipients. Interact Cardiovasc Thorac Surg. 2012;15(4):603–7.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Vanaudenaerde BM, Wuyts WA, Geudens N, Nawrot TS, Vos R, Dupont LJ, et al. Broncho-alveolar lavage fluid recovery correlates with airway neutrophilia in lung transplant patients. Respir Med. 2008;102(3):339–47.

    Article  PubMed  Google Scholar 

  20. Wu Q, Gupta PK, Suzuki H, Wagner SR, Zhang C, Cummings OW, et al. CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis. Am J Transplant. 2015;15(7):1793–804.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. O’Boyle G, Ali S, Kirby JA. Chemokines in transplantation: what can atypical receptors teach us about anti-inflammatory therapy? Transplant Rev. 2011;25(4):136–44.

    Article  Google Scholar 

  22. Husain S, Resende MR, Rajwans N, Zamel R, Pilewski JM, Crespo MM, et al. Elevated CXCL10 (IP-10) in bronchoalveolar lavage fluid is associated with acute cellular rejection after human lung transplantation. Transplantation. 2014;97(1):90–7.

    Article  PubMed  CAS  Google Scholar 

  23. Neujahr DC, Perez SD, Mohammed A, Ulukpo O, Lawrence EC, Fernandez F, et al. Cumulative exposure to gamma interferon-dependent chemokines CXCL9 and CXCL10 correlates with worse outcome after lung transplant. Am J Transplant. 2012;12(2):438–46.

    Article  PubMed  CAS  Google Scholar 

  24. Verleden SE, Ruttens D, Vos R, Vandermeulen E, Moelants E, Mortier A, et al. Differential cytokine, chemokine and growth factor expression in phenotypes of chronic lung allograft dysfunction. Transplantation. 2015;99(1):86–93.

    Article  CAS  PubMed  Google Scholar 

  25. Bach F, Hirschhorn K. Lymphocyte interaction: a potential histocompatibility test in vitro. Science. 1964;143(3608):813–4.

    Article  PubMed  CAS  Google Scholar 

  26. Tinckam K. Histocompatibility methods. Transplant Rev. 2009;23(2):80–93.

    Article  Google Scholar 

  27. Holl V, Schmidt S, Aubertin AM, Moog C. The major population of PHA-stimulated PBMC infected by R5 or X4 HIV variants after a single cycle of infection is predominantly composed of CD45RO+CD4+ T lymphocytes. Arch Virol. 2007;152(3):507–18.

    Article  PubMed  CAS  Google Scholar 

  28. Rodrigo E, Lopez-Hoyos M, Corral M, Fabrega E, Fernandez-Fresnedo G, San Segundo D, et al. ImmuKnow as a diagnostic tool for predicting infection and acute rejection in adult liver transplant recipients: a systematic review and meta-analysis. Liver Transpl. 2012;18(10):1245–53.

    Article  PubMed  Google Scholar 

  29. Torio A, Fernandez EJ, Montes-Ares O, Guerra RM, Perez MA, Checa MD. Lack of association of immune cell function test with rejection in kidney transplantation. Transplant Proc. 2011;43(6):2168–70.

    Article  PubMed  CAS  Google Scholar 

  30. Ling X, Xiong J, Liang W, Schroder PM, Wu L, Ju W, et al. Can immune cell function assay identify patients at risk of infection or rejection? A meta-analysis. Transplantation. 2012;93(7):737–43.

    Article  PubMed  Google Scholar 

  31. Reynaud-Gaubert M, Thomas P, Gregoire R, Badier M, Cau P, Sampol J, et al. Clinical utility of bronchoalveolar lavage cell phenotype analyses in the postoperative monitoring of lung transplant recipients. Eur J Cardiothorac Surg. 2002;21(1):60–6.

    Article  PubMed  Google Scholar 

  32. Neurohr C, Huppmann P, Samweber B, Leuschner S, Zimmermann G, Leuchte H, et al. Prognostic value of bronchoalveolar lavage neutrophilia in stable lung transplant recipients. J Heart Lung Transplant. 2009;28(5):468–74.

    Article  PubMed  Google Scholar 

  33. Clatworthy MR. Targeting B cells and antibody in transplantation. Am J Transplant. 2011;11(7):1359–67.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Martinu T, Howell DN, Palmer SM. Acute cellular rejection and humoral sensitization in lung transplant recipients. Semin Respir Crit Care Med. 2010;31(2):179–88.

    Article  PubMed  Google Scholar 

  35. Diebolder CA, Beurskens FJ, de Jong RN, Koning RI, Strumane K, Lindorfer MA, et al. Complement is activated by IgG hexamers assembled at the cell surface. Science. 2014;343(6176):1260–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Colvin RB, Smith RN. Antibody-mediated organ-allograft rejection. Nat Rev Immunol. 2005;5(10):807–17.

    Article  PubMed  CAS  Google Scholar 

  37. Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;5:520.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Albrecht EA, Chinnaiyan AM, Varambally S, Kumar-Sinha C, Barrette TR, Sarma JV, et al. C5a-induced gene expression in human umbilical vein endothelial cells. Am J Pathol. 2004;164(3):849–59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Al-Daccak R, Mooney N, Charron D. MHC class II signaling in antigen-presenting cells. Curr Opin Immunol. 2004;16(1):108–13.

    Article  PubMed  CAS  Google Scholar 

  40. Li F, Atz ME, Reed EF. Human leukocyte antigen antibodies in chronic transplant vasculopathy-mechanisms and pathways. Curr Opin Immunol. 2009;21(5):557–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Zhang X, Reed EF. HLA class I: an unexpected role in integrin beta4 signaling in endothelial cells. Hum Immunol. 2012;73(12):1239–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Jaramillo A, Smith CR, Maruyama T, Zhang L, Patterson GA, Mohanakumar T. Anti-HLA class I antibody binding to airway epithelial cells induces production of fibrogenic growth factors and apoptotic cell death: a possible mechanism for bronchiolitis obliterans syndrome. Hum Immunol. 2003;64(5):521–9.

    Article  PubMed  CAS  Google Scholar 

  43. Jindra PT, Zhang X, Mulder A, Claas F, Veale J, Jin YP, et al. Anti-HLA antibodies can induce endothelial cell survival or proliferation depending on their concentration. Transplantation. 2006;82(1 Suppl):S33–5.

    Article  PubMed  CAS  Google Scholar 

  44. Jindra PT, Jin YP, Rozengurt E, Reed EFHLA, class I. antibody-mediated endothelial cell proliferation via the mTOR pathway. J Immunol. 2008;180(4):2357–66.

    Article  PubMed  CAS  Google Scholar 

  45. Zhang X, Reed EF. Effect of antibodies on endothelium. Am J Transplant. 2009;9(11):2459–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Valenzuela NM, Reed EF. Antibodies in transplantation: the effects of HLA and non-HLA antibody binding and mechanisms of injury. Methods Mol Biol. 2013;1034:41–70.

    Article  PubMed  CAS  Google Scholar 

  47. Snyder LD, Wang Z, Chen DF, Reinsmoen NL, Finlen-Copeland CA, Davis WA, et al. Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients. Chest. 2013;144(1):226–33.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Morrell MR, Pilewski JM, Gries CJ, Pipeling MR, Crespo MM, Ensor CR, et al. De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation. J Heart Lung Transplant. 2014;33(12):1288–94.

    Article  PubMed  Google Scholar 

  49. Safavi S, Robinson DR, Soresi S, Carby M, Smith JD. De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant. 2014;33(12):1273–81.

    Article  PubMed  Google Scholar 

  50. Brugiere O, Suberbielle C, Thabut G, Lhuillier E, Dauriat G, Metivier AC, et al. Lung transplantation in patients with pretransplantation donor-specific antibodies detected by Luminex assay. Transplantation. 2013;95(5):761–5.

    Article  PubMed  CAS  Google Scholar 

  51. Smith JD, Ibrahim MW, Newell H, Danskine AJ, Soresi S, Burke MM, et al. Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation. J Heart Lung Transplant. 2014;33(10):1074–82.

    Article  PubMed  Google Scholar 

  52. Witt CA, Gaut JP, Yusen RD, Byers DE, Iuppa JA, Bennett Bain K, et al. Acute antibody-mediated rejection after lung transplantation. J Heart Lung Transplant. 2013;32(10):1034–40.

    Article  PubMed  Google Scholar 

  53. Palmer SM, Davis RD, Hadjiliadis D, Hertz MI, Howell DN, Ward FE, et al. Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome. Transplantation. 2002;74(6):799–804.

    Article  PubMed  CAS  Google Scholar 

  54. Girnita AL, Duquesnoy R, Yousem SA, Iacono AT, Corcoran TE, Buzoianu M, et al. HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction. Am J Transplant. 2005;5(1):131–8.

    Article  PubMed  CAS  Google Scholar 

  55. Ius F, Sommer W, Tudorache I, Kuhn C, Avsar M, Siemeni T, et al. Early donor-specific antibodies in lung transplantation: risk factors and impact on survival. J Heart Lung Transplant. 2014;33(12):1255–63.

    Article  PubMed  Google Scholar 

  56. Tikkanen JM, Singer LG, Kim SJ, Li Y, Binnie M, Chaparro C, et al. De Novo DQ donor-specific antibodies are associated with chronic lung allograft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2016;194(5):596–606.

    Article  PubMed  CAS  Google Scholar 

  57. Roux A, Bendib Le Lan I, Holifanjaniaina S, Thomas KA, Hamid AM, Picard C, et al. Antibody-mediated rejection in lung transplantation: clinical outcomes and donor-specific antibody characteristics. Am J Transplant. 2016;16(4):1216–28.

    Article  PubMed  CAS  Google Scholar 

  58. Ferry BL, Welsh KI, Dunn MJ, Law D, Proctor J, Chapel H, et al. Anti-cell surface endothelial antibodies in sera from cardiac and kidney transplant recipients: association with chronic rejection. Transpl Immunol. 1997;5(1):17–24.

    Article  PubMed  CAS  Google Scholar 

  59. Sun Q, Liu Z, Chen J, Chen H, Wen J, Cheng D, et al. Circulating anti-endothelial cell antibodies are associated with poor outcome in renal allograft recipients with acute rejection. Clin J Am Soc Nephrol. 2008;3(5):1479–86.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Sun Q, Cheng Z, Cheng D, Chen J, Ji S, Wen J, et al. De novo development of circulating anti-endothelial cell antibodies rather than pre-existing antibodies is associated with post-transplant allograft rejection. Kidney Int. 2011;79(6):655–62.

    Article  PubMed  CAS  Google Scholar 

  61. Angaswamy N, Saini D, Ramachandran S, Nath DS, Phelan D, Hachem R, et al. Development of antibodies to human leukocyte antigen precedes development of antibodies to major histocompatibility class I-related chain A and are significantly associated with development of chronic rejection after human lung transplantation. Hum Immunol. 2010;71(6):560–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Zhang Q, Cecka JM, Gjertson DW, Ge P, Rose ML, Patel JK, et al. HLA and MICA: targets of antibody-mediated rejection in heart transplantation. Transplantation. 2011;91(10):1153–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Luo L, Li Z, Wu W, Luo G, Mei H, Sun Z, et al. The effect of MICA antigens on kidney transplantation outcomes. Immunol Lett. 2013;156(1-2):54–8.

    Article  PubMed  CAS  Google Scholar 

  64. Dragun D, Muller DN, Brasen JH, Fritsche L, Nieminen-Kelha M, Dechend R, et al. Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med. 2005;352(6):558–69.

    Article  PubMed  CAS  Google Scholar 

  65. Giral M, Foucher Y, Dufay A, Van Huyen JP, Renaudin K, Moreau A, et al. Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss. Am J Transplant. 2013;13(10):2567–76.

    Article  PubMed  CAS  Google Scholar 

  66. Reinsmoen NL, Lai CH, Mirocha J, Cao K, Ong G, Naim M, et al. Increased negative impact of donor HLA-specific together with non-HLA-specific antibodies on graft outcome. Transplantation. 2014;97(5):595–601.

    Article  PubMed  CAS  Google Scholar 

  67. Arnaoutakis GJ, Eng HS, George TJ, Beaty CA, Merlo CA, Shah AS, et al. The impact of angiotensin II type 1 receptor auto-antibodies and early lung transplant outcomes. Am J Transplant. 2012;12(S3):170.

    Google Scholar 

  68. Reinsmoen NL, Mirocha J, Ensor C, Marrari M, Chaux GE, Lai C, Levine D, Zeevi A. A three center study reveals new insights into the impact of non-HLA antibodies on the acute rejection process in lung transplantation. J Heart Lung Transplant. 2015;34(4):S119–S20.

    Article  Google Scholar 

  69. Kalache S, Dinavahi R, Pinney S, Mehrotra A, Cunningham MW, Heeger PS. Anticardiac myosin immunity and chronic allograft vasculopathy in heart transplant recipients. J Immunol. 2011;187(2):1023–30.

    Article  PubMed  CAS  Google Scholar 

  70. Nath DS, Illias Basha H, Saini D, Ramachandran S, Ewald GA, Moazami N, Mohanakumar T. The important role of immune responses to self-antigen in pathogenesis of coronary artery vasculopathy following human cardiac transplantation. J Heart Lung Transplant. 2010;29(2):S84–S5.

    Article  Google Scholar 

  71. Angaswamy N, Klein C, Tiriveedhi V, Gaut J, Anwar S, Rossi A, et al. Immune responses to collagen-IV and fibronectin in renal transplant recipients with transplant glomerulopathy. Am J Transplant. 2014;14(3):685–93.

    Article  PubMed  CAS  Google Scholar 

  72. Joosten SA, Sijpkens YW, van Ham V, Trouw LA, van der Vlag J, van den Heuvel B, et al. Antibody response against the glomerular basement membrane protein agrin in patients with transplant glomerulopathy. Am J Transplant. 2005;5(2):383–93.

    Article  PubMed  CAS  Google Scholar 

  73. Tiriveedhi V, Gautam B, Sarma NJ, Askar M, Budev M, Aloush A, et al. Pre-transplant antibodies to Kalpha1 tubulin and collagen-V in lung transplantation: clinical correlations. J Heart Lung Transplant. 2013;32(8):807–14.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Hachem RR, Tiriveedhi V, Patterson GA, Aloush A, Trulock EP, Mohanakumar T. Antibodies to K-alpha 1 tubulin and collagen V are associated with chronic rejection after lung transplantation. Am J Transplant. 2012;12(8):2164–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Nath DS, Tiriveedhi V, Basha HI, Phelan D, Moazami N, Ewald GA, et al. A role for antibodies to human leukocyte antigens, collagen-V, and K-alpha1-Tubulin in antibody-mediated rejection and cardiac allograft vasculopathy. Transplantation. 2011;91(9):1036–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Jaramillo A, Naziruddin B, Zhang L, Reznik SI, Smith MA, Aloush AA, et al. Activation of human airway epithelial cells by non-HLA antibodies developed after lung transplantation: a potential etiological factor for bronchiolitis obliterans syndrome. Transplantation. 2001;71(7):966–76.

    Article  PubMed  CAS  Google Scholar 

  77. Burlingham WJ, Love RB, Jankowska-Gan E, Haynes LD, Xu Q, Bobadilla JL, et al. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest. 2007;117(11):3498–506.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. 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(7):4487–94.

    Article  PubMed  CAS  Google Scholar 

  79. Iwata T, Philipovskiy A, Fisher AJ, Presson RG Jr, Chiyo M, Lee J, et al. Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction. J Immunol. 2008;181(8):5738–47.

    Article  PubMed  CAS  Google Scholar 

  80. Hagedorn PH, Burton CM, Carlsen J, Steinbruchel D, Andersen CB, Sahar E, et al. Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies. Immunology. 2010;130(3):427–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Bharat A, Saini D, Steward N, Hachem R, Trulock EP, Patterson GA, et al. Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection. Ann Thorac Surg. 2010;90(4):1094–101.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Paantjens AW, van de Graaf EA, Kwakkel-van Erp JM, Hoefnagel T, van Ginkel WG, Fakhry F, et al. The induction of IgM and IgG antibodies against HLA or MICA after lung transplantation. Pulm Med. 2011;2011:432169.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Levine DJ, Glanville AR, Aboyoun C, Belperio J, Benden C, Berry GJ, et al. Antibody-mediated rejection of the lung: a consensus report of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2016;35(4):397–406.

    Article  PubMed  Google Scholar 

  84. Book BK, Agarwal A, Milgrom AB, Bearden CM, Sidner RA, Higgins NG, et al. New crossmatch technique eliminates interference by humanized and chimeric monoclonal antibodies. Transplant Proc. 2005;37(2):640–2.

    Article  PubMed  CAS  Google Scholar 

  85. Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969;280(14):735–9.

    Article  PubMed  CAS  Google Scholar 

  86. Grenzi PC, de Marco R, Silva RZ, Campos EF, Gerbase-DeLima M. Antibodies against denatured HLA class II molecules detected in luminex-single antigen assay. Hum Immunol. 2013;74(10):1300–3.

    Article  PubMed  CAS  Google Scholar 

  87. Kao KJ, Scornik JC, Small SJ. Enzyme-linked immunoassay for anti-HLA antibodies--an alternative to panel studies by lymphocytotoxicity. Transplantation. 1993;55(1):192–6.

    Article  PubMed  CAS  Google Scholar 

  88. Weinstock C, Schnaidt M. The complement-mediated prozone effect in the Luminex single-antigen bead assay and its impact on HLA antibody determination in patient sera. Int J Immunogenet. 2013;40(3):171–7.

    Article  PubMed  CAS  Google Scholar 

  89. Poli F, Benazzi E, Innocente A, Nocco A, Cagni N, Gianatti A, et al. Heart transplantation with donor-specific antibodies directed toward denatured HLA-A*02:01: a case report. Hum Immunol. 2011;72(11):1045–8.

    Article  PubMed  CAS  Google Scholar 

  90. Yabu JM, Higgins JP, Chen G, Sequeira F, Busque S, Tyan DB. C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation. Transplantation. 2011;91(3):342–7.

    Article  PubMed  CAS  Google Scholar 

  91. Zeevi A, Lunz J, Feingold B, Shullo M, Bermudez C, Teuteberg J, et al. Persistent strong anti-HLA antibody at high titer is complement binding and associated with increased risk of antibody-mediated rejection in heart transplant recipients. J Heart Lung Transplant. 2013;32(1):98–105.

    Article  PubMed  Google Scholar 

  92. Gebel HM, Bray RA, Nickerson P. Pre-transplant assessment of donor-reactive, HLA-specific antibodies in renal transplantation: contraindication vs. risk. Am J Transplant. 2003;3(12):1488–500.

    Article  PubMed  Google Scholar 

  93. Aubert V, Venetz JP, Pantaleo G, Pascual M. Low levels of human leukocyte antigen donor-specific antibodies detected by solid phase assay before transplantation are frequently clinically irrelevant. Hum Immunol. 2009;70(8):580–3.

    Article  PubMed  CAS  Google Scholar 

  94. Susal C, Dohler B, Sadeghi M, Ovens J, Opelz G. HLA antibodies and the occurrence of early adverse events in the modern era of transplantation: a collaborative transplant study report. Transplantation. 2009;87(9):1367–71.

    Article  PubMed  CAS  Google Scholar 

  95. Singh N, Djamali A, Lorentzen D, Pirsch JD, Leverson G, Neidlinger N, et al. Pretransplant donor-specific antibodies detected by single-antigen bead flow cytometry are associated with inferior kidney transplant outcomes. Transplantation. 2010;90(10):1079–84.

    Article  PubMed  CAS  Google Scholar 

  96. Everly MJ. Summarizing the use of donor specific anti-HLA antibody monitoring in transplant patients. Clin Transpl. 2011:333–6.

    Google Scholar 

  97. Sicard A, Amrouche L, Suberbielle C, Carmagnat M, Candon S, Thervet E, et al. Outcome of kidney transplantations performed with preformed donor-specific antibodies of unknown etiology. Am J Transplant. 2014;14(1):193–201.

    Article  PubMed  CAS  Google Scholar 

  98. Morath C, Opelz G, Zeier M, Susal C. Clinical relevance of HLA antibody monitoring after kidney transplantation. J Immunol Res. 2014;2014:845040.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Iwasaki K, Miwa Y, Ogawa H, Yazaki S, Iwamoto M, Furusawa T, et al. Comparative study on signal transduction in endothelial cells after anti-a/b and human leukocyte antigen antibody reaction: implication of accommodation. Transplantation. 2012;93(4):390–7.

    Article  PubMed  CAS  Google Scholar 

  101. Zipfel PF, Skerka C. Complement regulators and inhibitory proteins. Nat Rev Immunol. 2009;9(10):729–40.

    Article  PubMed  CAS  Google Scholar 

  102. Sorman A, Zhang L, Ding Z, Heyman B. How antibodies use complement to regulate antibody responses. Mol Immunol. 2014;61(2):79–88.

    Article  PubMed  CAS  Google Scholar 

  103. Dunkelberger JR, Song WC. Role and mechanism of action of complement in regulating T cell immunity. Mol Immunol. 2010;47(13):2176–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Abe M, Shibata K, Akatsu H, Shimizu N, Sakata N, Katsuragi T, et al. Contribution of anaphylatoxin C5a to late airway responses after repeated exposure of antigen to allergic rats. J Immunol. 2001;167(8):4651–60.

    Article  PubMed  CAS  Google Scholar 

  105. Baelder R, Fuchs B, Bautsch W, Zwirner J, Kohl J, Hoymann HG, et al. Pharmacological targeting of anaphylatoxin receptors during the effector phase of allergic asthma suppresses airway hyperresponsiveness and airway inflammation. J Immunol. 2005;174(2):783–9.

    Article  PubMed  CAS  Google Scholar 

  106. Agrawal A, Sinha A, Ahmad T, Aich J, Singh P, Sharma A, et al. Maladaptation of critical cellular functions in asthma: bioinformatic analysis. Physiol Genomics. 2009;40(1):1–7.

    Article  PubMed  CAS  Google Scholar 

  107. Drouin SM, Corry DB, Hollman TJ, Kildsgaard J, Wetsel RA. Absence of the complement anaphylatoxin C3a receptor suppresses Th2 effector functions in a murine model of pulmonary allergy. J Immunol. 2002;169(10):5926–33.

    Article  PubMed  CAS  Google Scholar 

  108. Wills-Karp M. Complement activation pathways: a bridge between innate and adaptive immune responses in asthma. Proc Am Thorac Soc. 2007;4(3):247–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Suzuki H, Lasbury ME, Fan L, Vittal R, Mickler EA, Benson HL, et al. Role of complement activation in obliterative bronchiolitis post-lung transplantation. J Immunol. 2013;191(8):4431–9.

    Article  PubMed  CAS  Google Scholar 

  110. Pratt JR, Basheer SA, Sacks SH. Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat Med. 2002;8(6):582–7.

    Article  PubMed  CAS  Google Scholar 

  111. Pavlov V, Raedler H, Yuan S, Leisman S, Kwan WH, Lalli PN, et al. Donor deficiency of decay-accelerating factor accelerates murine T cell-mediated cardiac allograft rejection. J Immunol. 2008;181(7):4580–9.

    Article  PubMed  CAS  Google Scholar 

  112. Ratajczak MZ, Reca R, Wysoczynski M, Kucia M, Baran JT, Allendorf DJ, et al. Transplantation studies in C3-deficient animals reveal a novel role of the third complement component (C3) in engraftment of bone marrow cells. Leukemia. 2004;18(9):1482–90.

    Article  PubMed  CAS  Google Scholar 

  113. Rao DA, Pober JS. Endothelial injury, alarmins, and allograft rejection. Crit Rev Immunol. 2008;28(3):229–48.

    Article  PubMed  CAS  Google Scholar 

  114. Goldstein I, Ben-Horin S, Li J, Bank I, Jiang H, Chess L. Expression of the alpha1beta1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells. J Clin Invest. 2003;112(9):1444–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Shimamoto A, Pohlman TH, Shomura S, Tarukawa T, Takao M, Shimpo H. Toll-like receptor 4 mediates lung ischemia-reperfusion injury. Ann Thorac Surg. 2006;82(6):2017–23.

    Article  PubMed  Google Scholar 

  116. Kaczorowski DJ, Tsung A, Billiar TR. Innate immune mechanisms in ischemia/reperfusion. Front Biosci (Elite Ed). 2009;1:91–8.

    Google Scholar 

  117. Tsung A, Sahai R, Tanaka H, Nakao A, Fink MP, Lotze MT, et al. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med. 2005;201(7):1135–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Oberbarnscheidt MH, Zecher D, Lakkis FG. The innate immune system in transplantation. Semin Immunol. 2011;23(4):264–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Kim JI, Lee MK IV, Moore DJ, Sonawane SB, Duff PE, O’Connor MR, et al. Regulatory T-cell counter-regulation by innate immunity is a barrier to transplantation tolerance. Am J Transplant. 2009;9(12):2736–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Kreisel D, Nava RG, Li W, Zinselmeyer BH, Wang B, Lai J, et al. In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. Proc Natl Acad Sci U S A. 2010;107(42):18073–8.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Gelman AE, Okazaki M, Sugimoto S, Li W, Kornfeld CG, Lai J, et al. CCR2 regulates monocyte recruitment as well as CD4 T1 allorecognition after lung transplantation. Am J Transplant. 2010;10(5):1189–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Dominguez PM, Ardavin C. Differentiation and function of mouse monocyte-derived dendritic cells in steady state and inflammation. Immunol Rev. 2010;234(1):90–104.

    Article  PubMed  CAS  Google Scholar 

  123. Heidecke CD, Araujo JL, Kupiec-Weglinski JW, Abbud-Filho M, Araneda D, Stadler J, et al. Lack of evidence for an active role for natural killer cells in acute rejection of organ allografts. Transplantation. 1985;40(4):441–4.

    Article  PubMed  CAS  Google Scholar 

  124. Maier S, Tertilt C, Chambron N, Gerauer K, Huser N, Heidecke CD, et al. Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28-/- mice. Nat Med. 2001;7(5):557–62.

    Article  PubMed  CAS  Google Scholar 

  125. Murphy WJ, Kumar V, Bennett M. Acute rejection of murine bone marrow allografts by natural killer cells and T cells. Differences in kinetics and target antigens recognized. J Exp Med. 1987;166(5):1499–509.

    Article  PubMed  CAS  Google Scholar 

  126. Nicotra ML, Powell AE, Rosengarten RD, Moreno M, Grimwood J, Lakkis FG, et al. A hypervariable invertebrate allodeterminant. Curr Biol. 2009;19(7):583–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Rosengarten RD, Nicotra ML. Model systems of invertebrate allorecognition. Curr Biol. 2011;21(2):R82–92.

    Article  PubMed  CAS  Google Scholar 

  128. Valapour M, Skeans MA, Smith JM, Edwards LB, Cherikh WS, Uccellini K, et al. OPTN/SRTR 2015 Annual Data Report: Lung. Am J Transplant. 2017;17(Suppl 1):357–424.

    Article  PubMed  Google Scholar 

  129. Snell GI, Holmes M, Levvey BJ, Shipp A, Robertson C, Westall GP, et al. Lessons and insights from ABO-incompatible lung transplantation. Am J Transplant. 2013;13(5):1350–3.

    Article  PubMed  CAS  Google Scholar 

  130. Pouliquen E, Koenig A, Chen CC, Sicard A, Rabeyrin M, Morelon E, et al. Recent advances in renal transplantation: antibody-mediated rejection takes center stage. F1000Prime Rep. 2015;7:51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Immunogenetics/HLA, Bloodworks Northwest, Seattle, WA, USA

    Idoia Gimferrer & Karen A. Nelson

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  1. Idoia Gimferrer
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  2. Karen A. Nelson
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  1. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine University of Washington, Seattle, Washington, USA

    Ganesh Raghu

  2. Department of Internal Medicine, University of Genoa, Genoa, Italy

    Roberto G. Carbone

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Gimferrer, I., Nelson, K.A. (2018). Immunology in Lung Transplantation. In: Raghu, G., Carbone, R. (eds) Lung Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-91184-7_9

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