Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease

Michaels, Paul J.; Espejo, Maria L.; Kobashigawa, Jon A.; Alejos, Juan; Burch, C.; Takemoto, S; Reed, Elaine F.; Fishbein, Michael C.

doi:10.1016/s1053-2498(02)00472-2

Cited by 363 publications

(319 citation statements)

References 24 publications

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“…The correlation between antibody absence and a low number of mismatched DRB1 eplets (Table 3) suggests many DR antigen mismatches may have a limited potential of inducing a humoral immune response. Another explanation for the low detection rate of circulating anti-HLA-DR antibodies is that they have been absorbed by the allograft which has been shown to express HLA-DR antigens on its endothelium and parenchymal cells [45][46][47][48] and that DRB antibodies can be eluted from rejected transplants [49]. Moreover, anti-DRB antibodies are more readily detected in class II sensitized patients in the absence of a transplanted organ (Table 2), and their frequency of antibody detection is similar to that of HLA-DQ.…”

Section: Discussionmentioning

confidence: 99%

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Duquesnoy

Awadalla

Lomago

et al. 2008

Transplant Immunology

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This report describes a detailed analysis how donor-specific HLA class II epitope mismatching affects antibody reactivity patterns in 75 solid organ transplant recipients with an in situ allograft and who were considered for retransplantation. Sera were tested for antibodies in a sensitive antigenbinding assay (Luminex) with single class II alleles. Their reactivity was analyzed with HLAMatchmaker, a structural matching algorithm that considers so-called eplets to define epitopes recognized by antibodies. Only 24% of the patients showed donor-specific anti-DRB1 antibodies and there was a significant correlation with a low number of mismatched DRB1 eplets. This low detection rate of anti-DRB1 antibodies may also be due to allograft absorption. In contrast, antibodies to DRB3/4/5 mismatches were more common. Especially, 83% of the DRB4 (DR53) mismatches resulted in detectable antibodies against an eplet uniquely found on DR53 antigens. Donor-specific DQB mismatches led to detectable anti-DQB antibodies with a frequency of 87%. Their specificity correlated with eplets uniquely found on DQ1-4. The incidence of antibodies induced by 2-digit DQA mismatches was 64% and several eplets appeared to play a dominant role. These findings suggest that both α and β chains of HLA-DQ heterodimers have immunogenic epitopes that can elicit specific antibodies. About one-third of the sera had anti-DP antibodies; they reacted primarily with two DPB eplets and an allelic pair of DPA eplets.These data demonstrate that HLA class II reactive sera display distinct specificity patterns associated with structurally defined epitopes on different HLA-D alleles.

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Section: Discussionmentioning

confidence: 99%

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Duquesnoy

Awadalla

Lomago

et al. 2008

Transplant Immunology

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“…Autoimmunity confers risk to the development of AMR and CAV. Antibodies against non-HLA antigens have gained attention in the pathogenesis of AMR and CAV [75][76][77]. Antibodies against cardiac self-antigens such as cardiac myosin and vimentin (cytoskeleton protein) are found to be associated with development of AMR and CAV and are considered to be independent risk factor for CAV [66][67][68].…”

Section: Immunologic Factorsmentioning

confidence: 99%

“…Development of donor specific HLA antibodies has been associated with chronic rejection. Both acute cellular rejection (ACR) and AMR have been inferred in the pathogenesis of allograft vasculopathy [76][77][78][79][80][81][82][83][84][85]. Higher incidence of CAV is noted in heart transplant recipients with history of AMR than recipients without the history [76,77,84].…”

Section: Immunologic Factorsmentioning

confidence: 99%

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Munagala¹,

Phancao²

2018

obm.transplant

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Heart transplant remains the gold standard therapy for patients with end stage heart disease and offers improved survival and quality of life. Significant progress has been achieved in improving one-year mortality after heart transplantation. Nonetheless, longterm graft survival has not changed significantly over the past few decades. Long term survival of heart transplant recipients is limited by chronic rejection, cardiac allograft vasculopathy (CAV), and malignancy. CAV is a major contributor for graft failure and mortality after the first year of in heart transplant recipients. CAV is a proliferative vasculopathy characterized by diffuse myointimal hyperplasia and progressive narrowing of the graft vessels. Both immune dependent and independent factors have been shown to contribute to the pathogenesis of CAV. Understanding these risk factors is essential in developing preventative and therapeutic strategies. Angiography with Intravascular ultrasound has become the key diagnostic tool in the early detection of CAV as well as prognostication. Echocardiographic assessment of allograft function in conjunction with coronary angiographic findings are used in assessing the severity of CAV. Adjustment of immunosuppression and statins remain the initial steps in the management of CAV. Retransplantation is the definitive treatment for severe CAV, however, the paucity of organs along with increased mortality associated with retransplantation makes it a less desirable option. Remarkable progress has been achieved in the understanding of pathogenesis, risk factors for CAV and plaque morphology. Nevertheless, significant knowledge gaps persist in scientific understanding of risk factors, pathogenesis, prevention and treatment of CAV. Further research is warranted to fill these gaps, develop diagnostic modalities to facilitate early detection of CAV, and management strategies to Improve graft tolerance and immune modulation. This review focuses on summarizing the pathogenesis and risk factors for CAV.

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“…This is referred to as humoral or antibody-mediated rejection (AMR). AMR is associated with a significantly worse survival rate and predisposes patients to coronary vasculopathy (64). The ISHLT grading system (Table 2) was recently revised to reflect the shift in clinical response to lower grades of rejection and provide recommendations for the histological recognition and immunohistological investigation of acute AMR (65,66).…”

Section: Acute Rejectionmentioning

confidence: 99%

“…This type of rejection is more severe, is often resistant to standard forms of rejection therapy and is associated with a worse prognosis than cellular rejection (64). Treatment protocols using high-dose steroids, cyclophosphamide and plasmapheresis have been associated with improved survival and graft function.…”

Section: Treatment Of Humoral Rejection or Amrmentioning

confidence: 99%

Canadian Cardiovascular Society Consensus Conference update on cardiac transplantation 2008: Executive Summary

Haddad

Isaac

Légaré

et al. 2009

Canadian Journal of Cardiology

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Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease

Cited by 363 publications

References 24 publications

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Canadian Cardiovascular Society Consensus Conference update on cardiac transplantation 2008: Executive Summary

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