Treatment of hyperacute antibody-mediated lung allograft rejection with eculizumab

Dawson, Kyle L.; Parulekar, Amit; Seethamraju, Harish

doi:10.1016/j.healun.2012.09.016

Cited by 69 publications

(31 citation statements)

References 3 publications

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“…Hyperacute rejection has been seen after single lung transplantation and after re-transplantation (48–51). While many patients die because of refractory graft failure despite intensive immunosuppression, a minority have survived and done well in the intermediate follow-up period (47, 48, 52). …”

Section: Clinical Features Of Amrmentioning

confidence: 99%

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Antibody-Mediated Rejection in Lung Transplantation

Kulkarni

Bemiss²,

Hachem

2015

Curr Transpl Rep

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There has been increasing awareness of antibody-mediated rejection (AMR) as an important cause of graft failure after lung transplantation in recent years. However, the diagnostic criteria for pulmonary AMR are not well defined. All four tenets of AMR in kidney and heart transplantation, graft dysfunction, complement component deposition, circulating donor-specific antibodies (DSA), and histopathologic changes consistent with AMR, are infrequently present in lung transplantation. Nonetheless, the lung transplant community has made important progress recognizing cases of AMR and developing a definition. However, AMR is often refractory to therapy resulting in graft failure and death. In this review, we discuss the progress and challenges in the diagnosis and therapeutic options for pulmonary AMR. In addition, we briefly examine emerging paradigms of C4d-negative AMR and chronic AMR, and conclude that significant progress is needed to mitigate the effects of humoral immune responses after lung transplantation.

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Section: Clinical Features Of Amrmentioning

confidence: 99%

“…Therefore, eculizumab, a monoclonal antibody to C5 that prevents the formation of the MAC, is an appealing option for the treatment of AMR (29, 52). …”

Section: Treatment Of Amrmentioning

confidence: 99%

Antibody-Mediated Rejection in Lung Transplantation

Kulkarni

Bemiss²,

Hachem

2015

Curr Transpl Rep

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“…Finally, our observation of a rapid ABMR treatment response with eculizumab may be relevant for ABMR in other solid organ transplant recipients, was as recently reported in lung transplants. 25 …”

Section: Discussionmentioning

confidence: 99%

Eculizumab to Treat Antibody-Mediated Rejection in a 7-Year-Old Kidney Transplant Recipient

et al. 2015

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We report on successful early eculizumab administration to treat acute antibody-mediated rejection (ABMR) in a highly sensitized kidney transplant recipient. The recipient is a 7-year-old boy who received, 6 months after a desensitization protocol with monthly intravenous immunoglobulin infusion, a second kidney transplant in the presence of low donor-specific antibodies (DSAs). Both pretransplant lymphocytotoxic and flow cytometric crossmatch were negative. Allograft function recovered promptly, with excellent initial function. On postoperative day (POD) 4, the child developed significant proteinuria with an acute rise in serum creatinine. Allograft biopsy showed severe acute ABMR. Intravenous eculizumab (600 mg), preceded by a single session of plasmapheresis, was administered on POD 5 and 12 along with a 4-day thymoglobulin course. After the first dose of eculizumab, a strikingly rapid normalization of allograft function with a decrease in proteinuria occurred. However, because circulating DSA levels remained elevated, the child received 3 doses of intravenous immunoglobulin (POD 15,16,and 17), with a significant subsequent decrease in DSA levels. At 9 months after transplant, the child continues to maintain excellent allograft function with undetectable circulating DSA levels. This unique case highlights the potential efficacy of using early eculizumab to rapidly reverse severe ABMR in pediatric transplantation, and therefore it suggests a novel therapeutic approach to treat acute ABMR.

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“…The patient was resistant to standard antibody-depleting therapies but recovered renal function after treatment with two doses of eculizumab. Additional cases have been reported of successful treatment of acute AMR in highly sensitized recipients of kidney (93, 94), kidney/pancreas (95), heart (96), lung (97), and intestine (98) transplants. In the largest published trial to date, prophylactic treatment of sensitized renal transplant patients with eculizumab in addition to plasmapheresis reduced the incidence of acute AMR at one year compared to historical controls (7.7% versus 42.2%), but it did not significantly reduce the incidence of chronic AMR at two years (99, 100).…”

Section: Complement-targeted Therapiesmentioning

confidence: 99%

The Complement System and Antibody-Mediated Transplant Rejection

Stites

Quintrec

Thurman

2015

The Journal of Immunology

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Complement activation is an important cause of tissue injury in patients with antibody mediated rejection (AMR) of transplanted organs. Complement activation triggers a strong inflammatory response, and also generates tissue-bound and soluble fragments that are clinically useful markers of inflammation. The detection of complement proteins deposited within transplanted tissues has become an indispensible biomarker of AMR, and several assays have recently been developed to measure complement activation by antibodies reactive to specific donor human leukocyte antigens (HLA) expressed within the transplant. Complement inhibitors have entered clinical use and have shown efficacy for the treatment of AMR. New methods of detecting complement activation within transplanted organs will improve our ability to diagnose and monitor AMR, and will also help guide the use of complement inhibitory drugs.

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Treatment of hyperacute antibody-mediated lung allograft rejection with eculizumab

Cited by 69 publications

References 3 publications

Antibody-Mediated Rejection in Lung Transplantation

Antibody-Mediated Rejection in Lung Transplantation

Eculizumab to Treat Antibody-Mediated Rejection in a 7-Year-Old Kidney Transplant Recipient

The Complement System and Antibody-Mediated Transplant Rejection

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