Anticardiac Myosin Immunity and Chronic Allograft Vasculopathy in Heart Transplant Recipients

Kalache, Safa; Dinavahi, Rajani; Pinney, Sean; Mehrotra, Anita; Cunningham, Madeleine W.; Heeger, Peter S.

doi:10.4049/jimmunol.1004195

Cited by 60 publications

(55 citation statements)

References 44 publications

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“…Some autoantibodies against myosin as well as other autoantigens have also been described to be negative predictors in myocarditis or DCM [40,43,47,[50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Passive transfer of affinity-purified anti-heart autoantibodies (AHA) from sera of patients with myocarditis induces experimental myocarditis in mice

Caforio

Angelini

Blank

et al. 2015

International Journal of Cardiology

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“…Some autoantibodies against myosin as well as other autoantigens have also been described to be negative predictors in myocarditis or DCM [40,43,47,[50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Passive transfer of affinity-purified anti-heart autoantibodies (AHA) from sera of patients with myocarditis induces experimental myocarditis in mice

Caforio

Angelini

Blank

et al. 2015

International Journal of Cardiology

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“…Additional studies support a contribution of non-HLA antibodies to pre-sensitization (7,13). More specifically, serum IgG reactivity to autoantigens such as cardiac myosin, vimentin, collagen, oxidized lipids and LG3 has been associated with increased rejection rates and reduced graft survival (14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 91%

Pre-Transplant IgG Reactivity to Apoptotic Cells Correlates With Late Kidney Allograft Loss.

Gao¹,

Moore²,

Porcheray³

et al. 2014

Transplantation

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Pre-existing serum antibodies have long been associated with graft loss in transplant candidates. While most studies have focused on HLA-specific antibodies, the contribution of non-HLAreactive antibodies has been largely overlooked. We have recently characterized monoclonal antibodies secreted by B cell clones derived from kidney allograft recipients with rejection that selectively bind to apoptotic cells. Here, we assessed the presence of such antibodies in pretransplant serum from 300 kidney transplant recipients and examined their contribution to the graft outcomes. Kaplan-Meier survival analysis revealed that patients with high pre-transplant IgG reactivity to apoptotic cells had a significantly increased rate of late graft loss. The effect was only apparent after approximately 1 year post-transplant. Moreover, the association between pretransplant IgG reactivity to apoptotic cells and graft loss was still significant after excluding patients with high reactivity to HLA. This reactivity was almost exclusively mediated by IgG1 and IgG3 with complement fixing and activating properties. Overall, our findings support the view that IgG reactivity to apoptotic cells contribute to pre-sensitization. Taking these antibodies into

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“…The phenomenon of tissue-restricted immunity leading to organ rejection has also been demonstrated in heart allograft, where antibodies against cardiac myosin have been shown to be pathogenic in chronic heart allograft rejection (49). Furthermore, immunization with cardiac myosin can lead to induction of chronic rejection in a syngeneic heart transplant model (50).…”

Section: Discussionmentioning

confidence: 97%

Lung-Restricted Antibodies Mediate Primary Graft Dysfunction and Prevent Allotolerance after Murine Lung Transplantation

Bharat¹,

Chiu²,

Zheng³

et al. 2016

Am J Respir Cell Mol Biol

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Over one-third of lung recipients have preexisting antibodies against lung-restricted antigens: collagen (Col) type V and K-a1 tubulin (KAT). Although clinical studies have shown association of these antibodies with primary graft dysfunction (PGD), their biological significance remains unclear. We tested whether preexisting lungrestricted antibodies can mediate PGD and prevent allotolerance. A murine syngeneic (C57BL/6) or allogeneic (C57BL/6 to BALB/c) left lung transplantation model was used. Rabbit polyclonal antibodies were produced against KAT and Col-V and injected pretransplantation. T cell frequency was analyzed using enzyme-linked immunospot, whereas alloantibodies were determined using flow cytometry. Wet:dry ratio, arterial oxygenation, and histology were used to determine PGD. Preexisting Col-V or KAT, but not isotype control, antibodies lead to dose-dependent development of PGD after syngeneic lung transplantation, as evidenced by poor oxygenation and increased wet:dry ratio. Histology confirmed alveolar and capillary edema. The native right lung remained unaffected. Epitope spreading was observed where KAT antibody treatment led to the development of IL-17-producing CD4 1 T cells and humoral response against Col-V, or vice versa. In contrast, isotype control antibody failed to induce Col-V-or KAT-specific cellular or humoral immunity. In addition, none of the mice developed immunity against a non-lung antigen, collagen type II. Preexisting lung-restricted antibodies, but not isotype control, prevented development of allotolerance using the MHC-related 1 and cytotoxic T-lymphocyteassociated protein 4-Ig regimen. Lung-restricted antibodies can induce both early and delayed lung graft dysfunction. These antibodies can also cause spreading of lung-restricted immunity and promote alloimmunity. Antibody-directed therapy to treat preexisting lung-restricted antibodies might reduce PGD after lung transplantation.

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Anticardiac Myosin Immunity and Chronic Allograft Vasculopathy in Heart Transplant Recipients

Cited by 60 publications

References 44 publications

Passive transfer of affinity-purified anti-heart autoantibodies (AHA) from sera of patients with myocarditis induces experimental myocarditis in mice

Passive transfer of affinity-purified anti-heart autoantibodies (AHA) from sera of patients with myocarditis induces experimental myocarditis in mice

Pre-Transplant IgG Reactivity to Apoptotic Cells Correlates With Late Kidney Allograft Loss.

Lung-Restricted Antibodies Mediate Primary Graft Dysfunction and Prevent Allotolerance after Murine Lung Transplantation

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