Download PDF
Semin Respir Crit Care Med 2013; 34(03): 320-335
DOI: 10.1055/s-0033-1348471
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acute Cellular and Antibody-Mediated Allograft Rejection

William McManigle
1   Division of Pulmonary and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina
,
Elizabeth N. Pavlisko
2   Department of Pathology, Duke University Medical Center, Durham, North Carolina
,
Tereza Martinu
1   Division of Pulmonary and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina
› Author Affiliations
Further Information

Publication History

Publication Date:
02 July 2013 (online)

    Permissions and Reprints

Abstract

Survival post–lung transplantation remains limited to ∼ 50% at 5 years, far below survival after other solid organ transplants. Allograft rejection is a major cause of this limited survival. At least a third of lung transplant recipients experience acute rejection within 1 year posttransplantation. Acute rejection, though rarely a direct cause of death, represents the principal risk factor for chronic rejection, which is the greatest obstacle to long-term post–lung transplant survival. This article reviews in detail the two major subtypes of acute rejection: acute cellular rejection (ACR) and antibody-mediated rejection (AMR). ACR is diagnosed primarily by bronchoscopic transbronchial biopsies and is defined as perivascular or peribronchiolar lymphocytic infiltrates in the absence of infection. AMR remains poorly defined but is thought to involve anti–donor antibodies, allograft dysfunction, and pathological evidence of lung tissue injury or deposition of complement. Pathophysiological mechanisms, clinical presentation, clinical significance, known risk factors, and treatment strategies are discussed. Additionally, the limitations of current diagnostic modalities for both ACR and AMR are explained. Emerging data on the importance of donor-specific and non-donor-specific anti–human leukocyte antigen (anti-HLA) antibodies as well as non-HLA antibodies are presented. Larger cohorts have improved statistical analyses in recent years, leading to a clearer understanding of important topics related to ACR and AMR. Further collaborative studies and multicenter trials will be key in further advancing lung transplantation knowledge and improving outcomes in years to come.

Keywords

lung transplantation - acute rejection - humoral rejection - antibody-mediated rejection
 

  • References

  • 1 Snyder LD, Palmer SM. Immune mechanisms of lung allograft rejection. SeminRespirCrit Care Med 2006; 27 (5) 534-543
    PubMedGoogle Scholar
  • 2 Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 6th ed. Philadelphia, PA: Elsevier; 2010
  • 3 Valujskikh A, Baldwin III WM, Fairchild RL. Recent progress and new perspectives in studying T cell responses to allografts. Am J Transplant 2010; 10 (5) 1117-1125
    CrossrefPubMedGoogle Scholar
  • 4 Gelman AE, Li W, Richardson SB , et al. Cutting edge: acute lung allograft rejection is independent of secondary lymphoid organs. J Immunol 2009; 182 (7) 3969-3973
    CrossrefPubMedGoogle Scholar
  • 5 Sato M, Hirayama S, Hwang DM , et al. The role of intrapulmonary de novo lymphoid tissue in obliterative bronchiolitis after lung transplantation. J Immunol 2009; 182 (11) 7307-7316
    CrossrefPubMedGoogle Scholar
  • 6 Csencsits KL, Bishop DK. Contrasting alloreactive CD4+ and CD8+ T cells: there's more to it than MHC restriction. Am J Transplant 2003; 3 (2) 107-115
    CrossrefPubMedGoogle Scholar
  • 7 Burlingham WJ, Love RB, Jankowska-Gan E , 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) 3498-3506
    CrossrefPubMedGoogle Scholar
  • 8 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 (8) 5631-5638
    PubMedGoogle Scholar
  • 9 Braun RK, Molitor-Dart M, Wigfield C , et al. Transfer of tolerance to collagen type V suppresses T-helper-cell-17 lymphocyte-mediated acute lung transplant rejection. Transplantation 2009; 88 (12) 1341-1348
    CrossrefPubMedGoogle Scholar
  • 10 Bharat A, Fields RC, Steward N, Trulock EP, Patterson GA, Mohanakumar T. CD4+25+ regulatory T cells limit Th1-autoimmunity by inducing IL-10 producing T cells following human lung transplantation. Am J Transplant 2006; 6 (8) 1799-1808
    CrossrefPubMedGoogle Scholar
  • 11 De Vito Dabbs A, Hoffman LA, Iacono AT, Zullo TG, McCurry KR, Dauber JH. Are symptom reports useful for differentiating between acute rejection and pulmonary infection after lung transplantation?. Heart Lung 2004; 33 (6) 372-380
    CrossrefPubMedGoogle Scholar
  • 12 Gotway MB, Dawn SK, Sellami D , et al. Acute rejection following lung transplantation: limitations in accuracy of thin-section CT for diagnosis. Radiology 2001; 221 (1) 207-212
    CrossrefPubMedGoogle Scholar
  • 13 Ng YL, Paul N, Patsios D , et al. Imaging of lung transplantation: review. AJR Am J Roentgenol 2009; 192 (3, Suppl): S1-S13 , quiz S14–S19
    CrossrefPubMedGoogle Scholar
  • 14 Van Muylem A, Mélot C, Antoine M, Knoop C, Estenne M. Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation. Thorax 1997; 52 (7) 643-647
    CrossrefPubMedGoogle Scholar
  • 15 Gordon IO, Bhorade S, Vigneswaran WT, Garrity ER, Husain AN. SaLUTaRy: survey of lung transplant rejection. J Heart Lung Transplant 2012; 31 (9) 972-979
    CrossrefPubMedGoogle Scholar
  • 16 Hasegawa T, Iacono AT, Yousem SA. The anatomic distribution of acute cellular rejection in the allograft lung. Ann Thorac Surg 2000; 69 (5) 1529-1531
    CrossrefPubMedGoogle Scholar
  • 17 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 (12) 1229-1242
    CrossrefPubMedGoogle Scholar
  • 18 Vanaudenaerde BM, Dupont LJ, Wuyts WA , et al. The role of interleukin-17 during acute rejection after lung transplantation. Eur Respir J 2006; 27 (4) 779-787
    CrossrefPubMedGoogle Scholar
  • 19 Bhorade SM, Yu A, Vigneswaran WT, Alex CG, Garrity ER. Elevation of interleukin-15 protein expression in bronchoalveolar fluid in acute lung allograft rejection. Chest 2007; 131 (2) 533-538
    CrossrefPubMedGoogle Scholar
  • 20 Ross DJ, Moudgil A, Bagga A , et al. Lung allograft dysfunction correlates with gamma-interferon gene expression in bronchoalveolar lavage. J Heart Lung Transplant 1999; 18 (7) 627-636
    CrossrefPubMedGoogle Scholar
  • 21 Patel JM, Hu H, Lu L , et al. Thioredoxin as a biomarker for graft rejection in lung transplant recipients. Biomarkers 2008; 13 (5) 486-495
    CrossrefPubMedGoogle Scholar
  • 22 Vos R, Vanaudenaerde BM, Verleden SE , et al. Bronchoalveolar lavage neutrophilia in acute lung allograft rejection and lymphocytic bronchiolitis. J Heart Lung Transplant 2010; 29 (11) 1259-1269
    CrossrefPubMedGoogle Scholar
  • 23 Gregson AL, Hoji A, Saggar R , et al. Bronchoalveolar immunologic profile of acute human lung transplant allograft rejection. Transplantation 2008; 85 (7) 1056-1059
    CrossrefPubMedGoogle Scholar
  • 24 Meehan AC, Sullivan LC, Mifsud NA , et al. Natural killer cell activation in the lung allograft early posttransplantation. Transplantation 2010; 89 (6) 756-763
    CrossrefPubMedGoogle Scholar
  • 25 Madsen CB, Nørgaard A, Iversen M, Ryder LP. Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts. Transpl Immunol 2010; 24 (1) 26-32
    CrossrefPubMedGoogle Scholar
  • 26 San Segundo D, Brunet M, Ballesteros MA , et al. Prospective study of biomarkers of immune response in lung transplant recipients. Transplant Proc 2012; 44 (9) 2666-2668
    CrossrefPubMedGoogle Scholar
  • 27 Patil J, Lande JD, Li N, Berryman TR, King RA, Hertz MI. Bronchoalveolar lavage cell gene expression in acute lung rejection: development of a diagnostic classifier. Transplantation 2008; 85 (2) 224-231
    CrossrefPubMedGoogle Scholar
  • 28 Chambers DC, Hodge S, Hodge G , et al. A novel approach to the assessment of lymphocytic bronchiolitis after lung transplantation—transbronchial brush. J Heart Lung Transplant 2011; 30 (5) 544-551
    CrossrefPubMedGoogle Scholar
  • 29 Hodge G, Hodge S, Chambers DC, Reynolds PN, Holmes M. Increased expression of graft intraepithelial T-cell pro-inflammatory cytokines compared with native lung during episodes of acute rejection. J Heart Lung Transplant 2012; 31 (5) 538-544
    CrossrefPubMedGoogle Scholar
  • 30 Kowalski RJ, Post DR, Mannon RB , et al. Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation 2006; 82 (5) 663-668
    PubMedGoogle Scholar
  • 31 Bhorade SM, Janata K, Vigneswaran WT, Alex CG, Garrity ER. Cylex ImmuKnow assay levels are lower in lung transplant recipients with infection. J Heart Lung Transplant 2008; 27 (9) 990-994
    CrossrefPubMedGoogle Scholar
  • 32 Husain S, Raza K, Pilewski JM , et al. Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection. Transplantation 2009; 87 (12) 1852-1857
    CrossrefPubMedGoogle Scholar
  • 33 Shino MY, Weigt SS, Saggar R , et al. Usefulness of immune monitoring in lung transplantation using adenosine triphosphate production in activated lymphocytes. J Heart Lung Transplant 2012; 31 (9) 996-1002
    CrossrefPubMedGoogle Scholar
  • 34 Chakinala MM, Ritter J, Gage BF , et al. Reliability for grading acute rejection and airway inflammation after lung transplantation. J Heart Lung Transplant 2005; 24 (6) 652-657
    CrossrefPubMedGoogle Scholar
  • 35 Stephenson A, Flint J, English J , et al. Interpretation of transbronchial lung biopsies from lung transplant recipients: inter- and intraobserver agreement. Can Respir J 2005; 12 (2) 75-77
    PubMedGoogle Scholar
  • 36 Colombat M, Groussard O, Lautrette A , et al. Analysis of the different histologic lesions observed in transbronchial biopsy for the diagnosis of acute rejection. Clinicopathologic correlations during the first 6 months after lung transplantation. Hum Pathol 2005; 36 (4) 387-394
    CrossrefPubMedGoogle Scholar
  • 37 Arcasoy SM, Berry G, Marboe CC , et al. Pathologic interpretation of transbronchial biopsy for acute rejection of lung allograft is highly variable. Am J Transplant 2011; 11 (2) 320-328
    CrossrefPubMedGoogle Scholar
  • 38 Hasegawa T, Iacono A, Yousem SA. The significance of bronchus-associated lymphoid tissue in human lung transplantation: is there an association with acute and chronic rejection?. Transplantation 1999; 67 (3) 381-385
    CrossrefPubMedGoogle Scholar
  • 39 Shenoy KV, Solomides C, Cordova F, Rogers TJ, Ciccolella D, Criner GJ. Low CD4/CD8 ratio in bronchus-associated lymphoid tissue is associated with lung allograft rejection. J Transplant 2012; 2012: 928081
    PubMedGoogle Scholar
  • 40 Christie JD, Edwards LB, Kucheryavaya AY , et al. The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Lung and Heart-Lung Transplant Report—2011. J Heart Lung Transplant 2011; 30 (10) 1104-1122
    CrossrefPubMedGoogle Scholar
  • 41 Burton CM, Iversen M, Carlsen J , et al. Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1. J Heart Lung Transplant 2009; 28 (9) 888-893
    CrossrefPubMedGoogle Scholar
  • 42 Sharples LD, McNeil K, Stewart S, Wallwork J. Risk factors for bronchiolitis obliterans: a systematic review of recent publications. J Heart Lung Transplant 2002; 21 (2) 271-281
    CrossrefPubMedGoogle Scholar
  • 43 Girgis RE, Tu I, Berry GJ , et al. Risk factors for the development of obliterative bronchiolitis after lung transplantation. J Heart Lung Transplant 1996; 15 (12) 1200-1208
    PubMedGoogle Scholar
  • 44 Bando K, Paradis IL, Similo S , et al. Obliterative bronchiolitis after lung and heart-lung transplantation. An analysis of risk factors and management. J Thorac Cardiovasc Surg 1995; 110 (1) 4-13 , discussion 13–14
    CrossrefPubMedGoogle Scholar
  • 45 Kim DW, Dacic S, Iacono A, Grgurich W, Yousem SA. Significance of a solitary perivascular mononuclear infiltrate in lung allograft recipients with mild acute cellular rejection. J Heart Lung Transplant 2005; 24 (2) 152-155
    CrossrefPubMedGoogle Scholar
  • 46 Burton CM, Iversen M, Scheike T, Carlsen J, Andersen CB. Minimal acute cellular rejection remains prevalent up to 2 years after lung transplantation: a retrospective analysis of 2697 transbronchial biopsies. Transplantation 2008; 85 (4) 547-553
    CrossrefPubMedGoogle Scholar
  • 47 DeVito Dabbs A, Hoffman LA, Iacono AT , et al. Pattern and predictors of early rejection after lung transplantation. Am J Crit Care 2003; 12 (6) 497-507
    PubMedGoogle Scholar
  • 48 Yousem SA. The potential role of mast cells in lung allograft rejection. Hum Pathol 1997; 28 (2) 179-182
    CrossrefPubMedGoogle Scholar
  • 49 Scholma J, Slebos DJ, Boezen HM , et al. Eosinophilic granulocytes and interleukin-6 level in bronchoalveolar lavage fluid are associated with the development of obliterative bronchiolitis after lung transplantation. Am J Respir Crit Care Med 2000; 162 (6) 2221-2225
    CrossrefPubMedGoogle Scholar
  • 50 Yousem SA, Martin T, Paradis IL, Keenan R, Griffith BP. Can immunohistological analysis of transbronchial biopsy specimens predict responder status in early acute rejection of lung allografts?. Hum Pathol 1994; 25 (5) 525-529
    CrossrefPubMedGoogle Scholar
  • 51 Glanville AR, Aboyoun CL, Havryk A, Plit M, Rainer S, Malouf MA. Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation. Am J Respir Crit Care Med 2008; 177 (9) 1033-1040
    CrossrefPubMedGoogle Scholar
  • 52 Husain AN, Siddiqui MT, Montoya A, Chandrasekhar AJ, Garrity ER. Post-lung transplant biopsies: an 8-year Loyola experience. Mod Pathol 1996; 9 (2) 126-132
    PubMedGoogle Scholar
  • 53 Irani S, Gaspert A, Vogt P , et al. Inflammation patterns in allogeneic and autologous airway tissue of lung transplant recipients. Am J Transplant 2005; 5 (10) 2456-2463
    CrossrefPubMedGoogle Scholar
  • 54 Ward C, Snell GI, Orsida B, Zheng L, Williams TJ, Walters EH. Airway versus transbronchial biopsy and BAL in lung transplant recipients: different but complementary. Eur Respir J 1997; 10 (12) 2876-2880
    CrossrefPubMedGoogle Scholar
  • 55 Xu X, Golden JA, Dolganov G , et al. Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimens. J Heart Lung Transplant 2005; 24 (8) 1055-1066
    CrossrefPubMedGoogle Scholar
  • 56 Greenland JR, Jones KD, Hays SR , et al. Association of Large-Airway Lymphocytic Bronchitis with Bronchiolitis Obliterans Syndrome. Am J Respir Crit Care Med 2013; 187 (4) 417-423
    CrossrefPubMedGoogle Scholar
  • 57 Davis WA, Finlen Copeland CA, Todd JL, Snyder LD, Martissa JA, Palmer SM. Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation. Am J Transplant 2012; 12 (3) 745-752
    CrossrefPubMedGoogle Scholar
  • 58 Schulman LL, Weinberg AD, McGregor C, Galantowicz ME, Suciu-Foca NM, Itescu S. Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation. Am J Respir Crit Care Med 1998; 157 (6, Pt 1) 1833-1837
    CrossrefPubMedGoogle Scholar
  • 59 Quantz MA, Bennett LE, Meyer DM, Novick RJ. Does human leukocyte antigen matching influence the outcome of lung transplantation? An analysis of 3,549 lung transplantations. J Heart Lung Transplant 2000; 19 (5) 473-479
    CrossrefPubMedGoogle Scholar
  • 60 Wisser W, Wekerle T, Zlabinger G , et al. Influence of human leukocyte antigen matching on long-term outcome after lung transplantation. J Heart Lung Transplant 1996; 15 (12) 1209-1216
    PubMedGoogle Scholar
  • 61 Mangi AA, Mason DP, Nowicki ER , et al. Predictors of acute rejection after lung transplantation. Ann Thorac Surg 2011; 91 (6) 1754-1762
    CrossrefPubMedGoogle Scholar
  • 62 Peltz M, Edwards LB, Jessen ME, Torres F, Meyer DM. HLA mismatches influence lung transplant recipient survival, bronchiolitis obliterans and rejection: implications for donor lung allocation. J Heart Lung Transplant 2011; 30 (4) 426-434
    CrossrefPubMedGoogle Scholar
  • 63 Opelz G, Süsal C, Ruhenstroth A, Döhler B. Impact of HLA compatibility on lung transplant survival and evidence for an HLA restriction phenomenon: a collaborative transplant study report. Transplantation 2010; 90 (8) 912-917
    PubMedGoogle Scholar
  • 64 Palmer SM, Baz MA, Sanders L , et al. Results of a randomized, prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection. Transplantation 2001; 71 (12) 1772-1776
    CrossrefPubMedGoogle Scholar
  • 65 Treede H, Glanville AR, Klepetko W , et al; European and Australian Investigators in Lung Transplantation. Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomized international trial in lung transplantation. J Heart Lung Transplant 2012; 31 (8) 797-804
    CrossrefPubMedGoogle Scholar
  • 66 Lischke R, Simonek J, Davidová R , et al. Induction therapy in lung transplantation: initial single-center experience comparing daclizumab and antithymocyte globulin. Transplant Proc 2007; 39 (1) 205-212
    CrossrefPubMedGoogle Scholar
  • 67 Gullestad L, Mortensen SA, Eiskjær H , et al. Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial. Transplantation 2010; 90 (12) 1581-1589
    CrossrefPubMedGoogle Scholar
  • 68 Bhorade S, Ahya VN, Baz MA , et al. Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation. Am J Respir Crit Care Med 2011; 183 (3) 379-387
    CrossrefPubMedGoogle Scholar
  • 69 Shyu S, Dew MA, Pilewski JM , et al. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transplant 2011; 30 (7) 743-754
    CrossrefPubMedGoogle Scholar
  • 70 Ahya VN, Douglas LP, Andreadis C , et al. Association between elevated whole blood Epstein-Barr virus (EBV)-encoded RNA EBV polymerase chain reaction and reduced incidence of acute lung allograft rejection. J Heart Lung Transplant 2007; 26 (8) 839-844
    CrossrefPubMedGoogle Scholar
  • 71 Zheng HX, Burckart GJ, McCurry K , et al. Interleukin-10 production genotype protects against acute persistent rejection after lung transplantation. J Heart Lung Transplant 2004; 23 (5) 541-546
    CrossrefPubMedGoogle Scholar
  • 72 Palmer SM, Burch LH, Trindade AJ , et al. Innate immunity influences long-term outcomes after human lung transplant. Am J Respir Crit Care Med 2005; 171 (7) 780-785
    CrossrefPubMedGoogle Scholar
  • 73 Girnita DM, Webber SA, Zeevi A. Clinical impact of cytokine and growth factor genetic polymorphisms in thoracic organ transplantation. Clin Lab Med 2008; 28 (3) 423-440 , vi
    CrossrefPubMedGoogle Scholar
  • 74 Colobran R, Casamitjana N, Roman A , et al. Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation. Genes Immun 2009; 10 (3) 254-259
    CrossrefPubMedGoogle Scholar
  • 75 Palmer SM, Klimecki W, Yu L , et al. Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. Am J Transplant 2007; 7 (3) 693-699
    CrossrefPubMedGoogle Scholar
  • 76 Zheng HX, Zeevi A, McCurry K , et al. The impact of pharmacogenomic factors on acute persistent rejection in adult lung transplant patients. Transpl Immunol 2005; 14 (1) 37-42
    CrossrefPubMedGoogle Scholar
  • 77 Gutierrez C, Al-Faifi S, Chaparro C , et al. The effect of recipient's age on lung transplant outcome. Am J Transplant 2007; 7 (5) 1271-1277
    CrossrefPubMedGoogle Scholar
  • 78 Mahidhara R, Bastani S, Ross DJ , et al. Lung transplantation in older patients?. J Thorac Cardiovasc Surg 2008; 135 (2) 412-420
    CrossrefPubMedGoogle Scholar
  • 79 Scott JP, Whitehead B, de Leval M , et al. Paediatric incidence of acute rejection and obliterative bronchiolitis: a comparison with adults. Transpl Int 1994; 7 (Suppl. 01) S404-S406
    CrossrefPubMedGoogle Scholar
  • 80 Ibrahim JE, Sweet SC, Flippin M , et al. Rejection is reduced in thoracic organ recipients when transplanted in the first year of life. J Heart Lung Transplant 2002; 21 (3) 311-318
    CrossrefPubMedGoogle Scholar
  • 81 Hartwig MG, Appel JZ, Li B , et al. Chronic aspiration of gastric fluid accelerates pulmonary allograft dysfunction in a rat model of lung transplantation. J Thorac Cardiovasc Surg 2006; 131 (1) 209-217
    CrossrefPubMedGoogle Scholar
  • 82 Shah N, Force SD, Mitchell PO , et al. Gastroesophageal reflux disease is associated with an increased rate of acute rejection in lung transplant allografts. Transplant Proc 2010; 42 (7) 2702-2706
    CrossrefPubMedGoogle Scholar
  • 83 Murthy SC, Nowicki ER, Mason DP , et al. Pretransplant gastroesophageal reflux compromises early outcomes after lung transplantation. J Thorac Cardiovasc Surg 2011; 142 (1) 47-52 , e3
    CrossrefPubMedGoogle Scholar
  • 84 Fisichella PM, Davis CS, Lundberg PW , et al. The protective role of laparoscopic antireflux surgery against aspiration of pepsin after lung transplantation. Surgery 2011; 150 (4) 598-606
    CrossrefPubMedGoogle Scholar
  • 85 Verleden SE, Scheers H, Nawrot TS , et al. Lymphocytic bronchiolitis after lung transplantation is associated with daily changes in air pollution. Am J Transplant 2012; 12 (7) 1831-1838
    CrossrefPubMedGoogle Scholar
  • 86 Kumar D, Husain S, Chen MH , et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation 2010; 89 (8) 1028-1033
    CrossrefPubMedGoogle Scholar
  • 87 Kumar D, Erdman D, Keshavjee S , et al. Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Am J Transplant 2005; 5 (8) 2031-2036
    CrossrefPubMedGoogle Scholar
  • 88 Vilchez RA, Dauber J, McCurry K, Iacono A, Kusne S. Parainfluenza virus infection in adult lung transplant recipients: an emergent clinical syndrome with implications on allograft function. Am J Transplant 2003; 3 (2) 116-120
    CrossrefPubMedGoogle Scholar
  • 89 Garantziotis S, Howell DN, McAdams HP, Davis RD, Henshaw NG, Palmer SM. Influenza pneumonia in lung transplant recipients: clinical features and association with bronchiolitis obliterans syndrome. Chest 2001; 119 (4) 1277-1280
    CrossrefPubMedGoogle Scholar
  • 90 Khalifah AP, Hachem RR, Chakinala MM , et al. Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death. Am J Respir Crit Care Med 2004; 170 (2) 181-187
    CrossrefPubMedGoogle Scholar
  • 91 Larcher C, Geltner C, Fischer H, Nachbaur D, Müller LC, Huemer HP. Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology. J Heart Lung Transplant 2005; 24 (11) 1891-1901
    CrossrefPubMedGoogle Scholar
  • 92 Soccal PM, Aubert JD, Bridevaux PO , et al. Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients. Clin Infect Dis 2010; 51 (2) 163-170
    CrossrefPubMedGoogle Scholar
  • 93 Vu DL, Bridevaux PO, Aubert JD, Soccal PM, Kaiser L. Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies. Am J Transplant 2011; 11 (5) 1071-1078
    CrossrefPubMedGoogle Scholar
  • 94 Weigt SS, Derhovanessian A, Liao E , et al. CXCR3 chemokine ligands during respiratory viral infections predict lung allograft dysfunction. Am J Transplant 2012; 12 (2) 477-484
    CrossrefPubMedGoogle Scholar
  • 95 Costa C, Delsedime L, Solidoro P , et al. Herpesviruses detection by quantitative real-time polymerase chain reaction in bronchoalveolar lavage and transbronchial biopsy in lung transplant: viral infections and histopathological correlation. Transplant Proc 2010; 42 (4) 1270-1274
    CrossrefPubMedGoogle Scholar
  • 96 Bergallo M, Costa C, Terlizzi ME , et al. Quantitative detection of the new polyomaviruses KI, WU and Merkel cell virus in transbronchial biopsies from lung transplant recipients. J Clin Pathol 2010; 63 (8) 722-725
    CrossrefPubMedGoogle Scholar
  • 97 Astegiano S, Bergallo M, Solidoro P , et al. Prevalence and clinical impact of polyomaviruses KI and WU in lung transplant recipients. Transplant Proc 2010; 42 (4) 1275-1278
    CrossrefPubMedGoogle Scholar
  • 98 Palmer SM, Limaye AP, Banks M , et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial. Ann Intern Med 2010; 152 (12) 761-769
    CrossrefPubMedGoogle Scholar
  • 99 Yamamoto S, Nava RG, Zhu J , et al. Cutting edge: Pseudomonas aeruginosa abolishes established lung transplant tolerance by stimulating B7 expression on neutrophils. J Immunol 2012; 189 (9) 4221-4225
    CrossrefPubMedGoogle Scholar
  • 100 Shields RK, Clancy CJ, Minces LR , et al. Staphylococcus aureus infections in the early period after lung transplantation: epidemiology, risk factors, and outcomes. J Heart Lung Transplant 2012; 31 (11) 1199-1206
    CrossrefPubMedGoogle Scholar
  • 101 Glanville AR, Gencay M, Tamm M , et al. Chlamydia pneumoniae infection after lung transplantation. J Heart Lung Transplant 2005; 24 (2) 131-136
    CrossrefPubMedGoogle Scholar
  • 102 Clelland C, Higenbottam T, Stewart S , et al. Bronchoalveolar lavage and transbronchial lung biopsy during acute rejection and infection in heart-lung transplant patients. Studies of cell counts, lymphocyte phenotypes, and expression of HLA-DR and interleukin-2 receptor. Am Rev Respir Dis 1993; 147 (6 Pt 1) 1386-1392
    CrossrefPubMedGoogle Scholar
  • 103 Lau CL, Palmer SM, D'Amico TA, Tapson VF, Davis RD. Lung transplantation at Duke University Medical Center. Clin Transpl 1998; 327-340
    PubMedGoogle Scholar
  • 104 Fuehner T, Simon A, Dierich M , et al. Indicators for steroid response in biopsy proven acute graft rejection after lung transplantation. Respir Med 2009; 103 (8) 1114-1121
    CrossrefPubMedGoogle Scholar
  • 105 Vitulo P, Oggionni T, Cascina A , et al. Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation. J Heart Lung Transplant 2002; 21 (4) 435-439
    CrossrefPubMedGoogle Scholar
  • 106 Sarahrudi K, Estenne M, Corris P , et al. International experience with conversion from cyclosporine to tacrolimus for acute and chronic lung allograft rejection. J Thorac Cardiovasc Surg 2004; 127 (4) 1126-1132
    CrossrefPubMedGoogle Scholar
  • 107 Shennib H, Massard G, Reynaud M, Noirclerc M. Efficacy of OKT3 therapy for acute rejection in isolated lung transplantation. J Heart Lung Transplant 1994; 13 (3) 514-519
    PubMedGoogle Scholar
  • 108 Reams BD, Musselwhite LW, Zaas DW , et al. Alemtuzumab in the treatment of refractory acute rejection and bronchiolitis obliterans syndrome after human lung transplantation. Am J Transplant 2007; 7 (12) 2802-2808
    CrossrefPubMedGoogle Scholar
  • 109 Keenan RJ, Iacono A, Dauber JH , et al. Treatment of refractory acute allograft rejection with aerosolized cyclosporine in lung transplant recipients. J Thorac Cardiovasc Surg 1997; 113 (2) 335-340 , discussion 340–341
    CrossrefPubMedGoogle Scholar
  • 110 Iacono A, Dauber J, Keenan R , et al. Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine. Transplantation 1997; 64 (2) 263-269
    CrossrefPubMedGoogle Scholar
  • 111 Dall'Amico R, Murer L. Extracorporeal photochemotherapy: a new therapeutic approach for allograft rejection. Transfus Apheresis Sci 2002; 26 (3) 197-204
    CrossrefPubMedGoogle Scholar
  • 112 Valentine VG, Robbins RC, Wehner JH, Patel HR, Berry GJ, Theodore J. Total lymphoid irradiation for refractory acute rejection in heart-lung and lung allografts. Chest 1996; 109 (5) 1184-1189
    CrossrefPubMedGoogle Scholar
  • 113 Tait BD, Süsal C, Gebel HM , et al. Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation 2013; 95 (1) 19-47
    CrossrefPubMedGoogle Scholar
  • 114 Colvin RB, Smith RN. Antibody-mediated organ-allograft rejection. Nat Rev Immunol 2005; 5 (10) 807-817
    CrossrefPubMedGoogle Scholar
  • 115 Stegall MD, Chedid MF, Cornell LD. The role of complement in antibody-mediated rejection in kidney transplantation. Nat Rev Nephrol 2012; 8 (11) 670-678
    CrossrefPubMedGoogle Scholar
  • 116 Takenaka M, Subramanian V, Tiriveedhi V , et al. Complement activation is not required for obliterative airway disease induced by antibodies to major histocompatibility complex class I: Implications for chronic lung rejection. J Heart Lung Transplant 2012; 31 (11) 1214-1222
    CrossrefPubMedGoogle Scholar
  • 117 Campo-Cañaveral de la Cruz JL, Naranjo JM, Salas C, Varela de Ugarte A. Fulminant hyperacute rejection after unilateral lung transplantation. Eur J Cardiothorac Surg 2012; 42 (2) 373-375
    CrossrefPubMedGoogle Scholar
  • 118 Bittner HB, Dunitz J, Hertz M, Bolman III MR, Park SJ. Hyperacute rejection in single lung transplantation—case report of successful management by means of plasmapheresis and antithymocyte globulin treatment. Transplantation 2001; 71 (5) 649-651
    CrossrefPubMedGoogle Scholar
  • 119 Neumann J, Tarrasconi H, Bortolotto A , et al. Acute humoral rejection in a lung recipient: reversion with bortezomib. Transplantation 2010; 89 (1) 125-126
    CrossrefPubMedGoogle Scholar
  • 120 Stuckey LJ, Kamoun M, Chan KM. Lung transplantation across donor-specific anti-human leukocyte antigen antibodies: utility of bortezomib therapy in early graft dysfunction. Ann Pharmacother 2012; 46 (1) e2
    CrossrefPubMedGoogle Scholar
  • 121 Campion EW. A death at Duke. N Engl J Med 2003; 348 (12) 1083-1084
    CrossrefPubMedGoogle Scholar
  • 122 Pierson III RN, Loyd JE, Goodwin A , et al. Successful management of an ABO-mismatched lung allograft using antigen-specific immunoadsorption, complement inhibition, and immunomodulatory therapy. Transplantation 2002; 74 (1) 79-84
    CrossrefPubMedGoogle Scholar
  • 123 Patel M, Carby M, Rice A, Cummins D, Banner NR. Medium-term outcome of an ABO incompatible lung transplant. Am J Transplant 2010; 10 (3) 702-703
    CrossrefPubMedGoogle Scholar
  • 124 Strüber M, Warnecke G, Hafer C , et al. Intentional ABO-incompatible lung transplantation. Am J Transplant 2008; 8 (11) 2476-2478
    CrossrefPubMedGoogle Scholar
  • 125 Yousem SA, Zeevi A. The histopathology of lung allograft dysfunction associated with the development of donor-specific HLA alloantibodies. Am J Surg Pathol 2012; 36 (7) 987-992
    CrossrefPubMedGoogle Scholar
  • 126 Berry G, Burke M, Andersen C , et al. Pathology of pulmonary antibody-mediated rejection: 2012 update from the Pathology Council of the ISHLT. J Heart Lung Transplant 2013; 32 (1) 14-21
    CrossrefPubMedGoogle Scholar
  • 127 Astor TL, Weill D, Cool C, Teitelbaum I, Schwarz MI, Zamora MR. Pulmonary capillaritis in lung transplant recipients: treatment and effect on allograft function. J Heart Lung Transplant 2005; 24 (12) 2091-2097
    CrossrefPubMedGoogle Scholar
  • 128 Khan MA, Nicolls MR. Complement-mediated microvascular injury leads to chronic rejection. Adv Exp Med Biol 2013; 735: 233-246
    PubMedGoogle Scholar
  • 129 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) 521-529
    CrossrefPubMedGoogle Scholar
  • 130 Saini D, Angaswamy N, Tiriveedhi V , et al. Synergistic effect of antibodies to human leukocyte antigens and defensins in pathogenesis of bronchiolitis obliterans syndrome after human lung transplantation. J Heart Lung Transplant 2010; 29 (12) 1330-1336
    CrossrefPubMedGoogle Scholar
  • 131 Maruyama T, Jaramillo A, Narayanan K, Higuchi T, Mohanakumar T. Induction of obliterative airway disease by anti-HLA class I antibodies. Am J Transplant 2005; 5 (9) 2126-2134
    CrossrefPubMedGoogle Scholar
  • 132 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 (1) 309-318
    PubMedGoogle Scholar
  • 133 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) 4487-4494
    PubMedGoogle Scholar
  • 134 Iwata T, Philipovskiy A, Fisher AJ , et al. Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction. J Immunol 2008; 181 (8) 5738-5747
    PubMedGoogle Scholar
  • 135 Tiriveedhi V, Angaswamy N, Weber J, Mohanakumar T. Lipid raft facilitated ligation of K-alpha1-tubulin by specific antibodies on epithelial cells: role in pathogenesis of chronic rejection following human lung transplantation. Biochem Biophys Res Commun 2010; 399 (2) 251-255
    CrossrefPubMedGoogle Scholar
  • 136 McKenna RM, Takemoto SK, Terasaki PI. Anti-HLA antibodies after solid organ transplantation. Transplantation 2000; 69 (3) 319-326
    CrossrefPubMedGoogle Scholar
  • 137 Pei R, Lee JH, Shih NJ, Chen M, Terasaki PI. Single human leukocyte antigen flow cytometry beads for accurate identification of human leukocyte antigen antibody specificities. Transplantation 2003; 75 (1) 43-49
    CrossrefPubMedGoogle Scholar
  • 138 Cecka JM. Calculated PRA (CPRA): the new measure of sensitization for transplant candidates. Am J Transplant 2010; 10 (1) 26-29
    CrossrefPubMedGoogle Scholar
  • 139 Liu C, Wetter L, Pang S, Phelan DL, Mohanakumar T, Morris GP. Cutoff values and data handling for solid-phase testing for antibodies to HLA: effects on listing unacceptable antigens for thoracic organ transplantation. Hum Immunol 2012; 73 (6) 597-604
    CrossrefPubMedGoogle Scholar
  • 140 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) 342-347
    CrossrefPubMedGoogle Scholar
  • 141 Chin C, Chen G, Sequeria F , et al. Clinical usefulness of a novel C1q assay to detect immunoglobulin G antibodies capable of fixing complement in sensitized pediatric heart transplant patients. J Heart Lung Transplant 2011; 30 (2) 158-163
    CrossrefPubMedGoogle Scholar
  • 142 Appel III JZ, Hartwig MG, Davis RD, Reinsmoen NL. Utility of peritransplant and rescue intravenous immunoglobulin and extracorporeal immunoadsorption in lung transplant recipients sensitized to HLA antigens. Hum Immunol 2005; 66 (4) 378-386
    CrossrefPubMedGoogle Scholar
  • 143 Hachem RR, Yusen RD, Meyers BF , et al. Anti-human leukocyte antigen antibodies and preemptive antibody-directed therapy after lung transplantation. J Heart Lung Transplant 2010; 29 (9) 973-980
    CrossrefPubMedGoogle Scholar
  • 144 Appel III JZ, Hartwig MG, Cantu III E, Palmer SM, Reinsmoen NL, Davis RD. Role of flow cytometry to define unacceptable HLA antigens in lung transplant recipients with HLA-specific antibodies. Transplantation 2006; 81 (7) 1049-1057
    CrossrefPubMedGoogle Scholar
  • 145 Taylor CJ, Smith SI, Morgan CH , et al. Selective omission of the donor cross-match before renal transplantation: efficacy, safety and effects on cold storage time. Transplantation 2000; 69 (5) 719-723
    PubMedGoogle Scholar
  • 146 Lobo LJ, Aris RM, Schmitz J, Neuringer IP. Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation. J Heart Lung Transplant 2013; 32 (1) 70-77
    CrossrefPubMedGoogle Scholar
  • 147 Snyder LD, Wang Z, Chen DF , et al. Implications for human leukocyte antigen antibodies after lung transplantation: a 10 year experience in 441 patients. Chest 2013;
    PubMedGoogle Scholar
  • 148 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 (10) 1135-1141
    CrossrefPubMedGoogle Scholar
  • 149 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 (1) 131-138
    CrossrefPubMedGoogle Scholar
  • 150 Palmer SM, Davis RD, Hadjiliadis D , 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
    CrossrefPubMedGoogle Scholar
  • 151 Hadjiliadis D, Chaparro C, Reinsmoen NL , et al. Pre-transplant panel reactive antibody in lung transplant recipients is associated with significantly worse post-transplant survival in a multicenter study. J Heart Lung Transplant 2005; 24 (7, Suppl): S249-S254
    CrossrefPubMedGoogle Scholar
  • 152 Shah AS, Nwakanma L, Simpkins C, Williams J, Chang DC, Conte JV. Pretransplant panel reactive antibodies in human lung transplantation: an analysis of over 10,000 patients. Ann Thorac Surg 2008; 85 (6) 1919-1924
    CrossrefPubMedGoogle Scholar
  • 153 Saini D, Weber J, Ramachandran S , et al. Alloimmunity-induced autoimmunity as a potential mechanism in the pathogenesis of chronic rejection of human lung allografts. J Heart Lung Transplant 2011; 30 (6) 624-631
    CrossrefPubMedGoogle Scholar
  • 154 Smith JD, Crisp SJ, Dunn MJ, Pomerance A, Yacoub MH, Rose ML. Pre-transplant anti-epithelial cell antibodies and graft failure after single lung transplantation. Transpl Immunol 1995; 3 (1) 68-73
    CrossrefPubMedGoogle Scholar
  • 155 Magro CM, Klinger DM, Adams PW , et al. Evidence that humoral allograft rejection in lung transplant patients is not histocompatibility antigen-related. Am J Transplant 2003; 3 (10) 1264-1272
    CrossrefPubMedGoogle Scholar
  • 156 Angaswamy N, Saini D, Ramachandran S , 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) 560-565
    CrossrefPubMedGoogle Scholar
  • 157 Bharat A, Saini D, Steward N , et al. Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection. Ann Thorac Surg 2010; 90 (4) 1094-1101
    CrossrefPubMedGoogle Scholar
  • 158 Otten HG, van den Bosch JM, van Ginkel WG, van Loon M, van de Graaf EA. Identification of non-HLA target antigens recognized after lung transplantation. J Heart Lung Transplant 2006; 25 (12) 1425-1430
    CrossrefPubMedGoogle Scholar
  • 159 Saint Martin GA, Reddy VB, Garrity ER , et al. Humoral (antibody-mediated) rejection in lung transplantation. J Heart Lung Transplant 1996; 15 (12) 1217-1222
    PubMedGoogle Scholar
  • 160 Magro CM, Deng A, Pope-Harman A , et al. Humorally mediated posttransplantation septal capillary injury syndrome as a common form of pulmonary allograft rejection: a hypothesis. Transplantation 2002; 74 (9) 1273-1280
    CrossrefPubMedGoogle Scholar
  • 161 Miller GG, Destarac L, Zeevi A , et al. Acute humoral rejection of human lung allografts and elevation of C4d in bronchoalveolar lavage fluid. Am J Transplant 2004; 4 (8) 1323-1330
    CrossrefPubMedGoogle Scholar
  • 162 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 (10) 1565-1570
    CrossrefPubMedGoogle Scholar
  • 163 Ionescu DN, Girnita AL, Zeevi A , et al. C4d deposition in lung allografts is associated with circulating anti-HLA alloantibody. Transpl Immunol 2005; 15 (1) 63-68
    CrossrefPubMedGoogle Scholar
  • 164 Girnita AL, McCurry KR, Yousem SA, Pilewski J, Zeevi A. Antibody-mediated rejection in lung transplantation: case reports. Clin Transpl 2006; 508-510
    PubMedGoogle Scholar
  • 165 Magro CM, Abbas AE, Seilstad K, Pope-Harman AL, Nadasdy T, Ross Jr P. C3d and the septal microvasculature as a predictor of chronic lung allograft dysfunction. Hum Immunol 2006; 67 (4-5) 274-283
    CrossrefPubMedGoogle Scholar
  • 166 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 (7) 722-728
    CrossrefPubMedGoogle Scholar
  • 167 Golocheikine A, Nath DS, Basha HI , et al. Increased erythrocyte C4D is associated with known alloantibody and autoantibody markers of antibody-mediated rejection in human lung transplant recipients. J Heart Lung Transplant 2010; 29 (4) 410-416
    CrossrefPubMedGoogle Scholar
  • 168 Roberts DM, Jiang SH, Chadban SJ. The treatment of acute antibody-mediated rejection in kidney transplant recipients-a systematic review. Transplantation 2012; 94 (8) 775-783
    PubMedGoogle Scholar
  • 169 Vo AA, Lukovsky M, Toyoda M , et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 2008; 359 (3) 242-251
    CrossrefPubMedGoogle Scholar
  • 170 Hachem RR, Tiriveedhi V, Patterson GA, Aloush A, Trulock EP, Mohanakumar T. Antibodies to K-α 1 tubulin and collagen V are associated with chronic rejection after lung transplantation. Am J Transplant 2012; 12 (8) 2164-2171
    CrossrefPubMedGoogle Scholar
  • 171 Lemy A, Toungouz M, Abramowicz D. Bortezomib: a new player in pre- and post-transplant desensitization?. Nephrol Dial Transplant 2010; 25 (11) 3480-3489
    CrossrefPubMedGoogle Scholar
  • 172 Woodle ES, Alloway RR, Girnita A. Proteasome inhibitor treatment of antibody-mediated allograft rejection. Curr Opin Organ Transplant 2011; 16 (4) 434-438
    CrossrefPubMedGoogle Scholar
  • 173 Stegall MD, Diwan T, Raghavaiah S , et al. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant 2011; 11 (11) 2405-2413
    CrossrefPubMedGoogle Scholar