Cardiac Myosin Autoantibodies and Acute Rejection After Heart Transplantation in Patients With Dilated Cardiomyopathy

Warraich, Rahat S.; Pomerance, Ariela; Stanley, Adrian; Banner, Nicholas R.; Dünn, Michael J.; Yacoub, Magdi H.

doi:10.1097/00007890-200004270-00015

Cited by 65 publications

(47 citation statements)

References 31 publications

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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: 90%

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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Section: Introductionmentioning

confidence: 90%

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

Gao¹,

Moore²,

Porcheray³

et al. 2014

Transplantation

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“…31 In mice, antibodies to myosin accompany acute and chronic rejection. 32,33 All of these studies suggest that an initial insult to the graft may lead to an increased range of antigens to expand the antibody responses.…”

Section: Crosslinking Of Major Histocompatibility Complex Antigens Anmentioning

confidence: 99%

Antibody and Complement in Transplant Vasculopathy

Wehner

Morrell

Reynolds

et al. 2007

Circulation Research

109

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Abstract-Advances in immunosuppression have decreased the incidence of acute rejection, but the development of vasculopathy in the coronary arteries of transplants continues to limit the survival of cardiac allografts. Transplant vasculopathy has also been referred to as accelerated graft arteriosclerosis because it has features of arteriosclerosis, but it is limited to the graft and develops over a period of months to years. Although the pathological features of transplant vasculopathy are well defined, the causative mechanisms are not completely understood. This review focuses on the mechanisms by which antibody and complement can cause or contribute to coronary vasculopathy in cardiac transplants. Antibodies and complement can have independent effects, but the combination of antibodies and complement with inflammatory cells has greater pathogenic potential for the endothelial and smooth muscle cells of the coronary arteries.

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“…10,11 Tissue damage accompanying end-stage organ failure, regardless of etiology, could expose physiologically sequestered antigens to the immune system, breaking self-tolerance. 12 Mounting associative evidence suggests that such pretransplant autoimmunity to myosin, among other antigens, contributes to post-transplant graft injury. 13,14 In addition to pre-existing autoimmunity, ischemia reperfusion injury and tissue healing necessitated by transplant surgery, along with anti-donor alloimmunity, result in inflammation [15][16][17][18] and ex-posure of cryptic or sequestered self-antigens to the immune system.…”

mentioning

confidence: 99%

Antibodies Reactive to Non-HLA Antigens in Transplant Glomerulopathy

Dinavahi¹,

George

Tretin³

et al. 2011

Journal of the American Society of Nephrology

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Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidneyexpressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre-and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy. The screening studies identified three reactivities present before transplantation that persisted after transplant and strongly associated with transplant glomerulopathy. ELISA confirmed that reactivity against peroxisomal-trans-2-enoyl-coA-reductase strongly associated with the development of transplant glomerulopathy in independent validation sets. In addition to providing insight into effects of transplantation on non-HLA antibody repertoires, these results suggest that pretransplant serum antibodies to peroxisomal-trans-2-enoyl-coA-reductase may predict prognosis in kidney transplantation.

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Cardiac Myosin Autoantibodies and Acute Rejection After Heart Transplantation in Patients With Dilated Cardiomyopathy

Abstract: Proinflammatory characteristics of preformed IgG3 and IgM antibodies in DCM patients may influence the frequency and severity of cardiac rejection after transplantation.

Cited by 65 publications

References 31 publications

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

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

Antibody and Complement in Transplant Vasculopathy

Antibodies Reactive to Non-HLA Antigens in Transplant Glomerulopathy

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