De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation

Morrell, Matthew R.; Pilewski, Joseph M.; Gries, Cynthia J.; Pipeling, Matthew R.; Crespo, Maria; Ensor, Christopher R.; Yousem, Samuel A.; D’Cunha, Jonathan; Shigemura, Norihisa; Bermúdez, C.; McDyer, John F.; Zeevi, Adriana

doi:10.1016/j.healun.2014.07.018

Cited by 148 publications

(123 citation statements)

References 24 publications

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“…Recipients may have pre-existing HLA antibodies as a result of pregnancy, previous transfusion, or organ transplantation, or may develop HLA antibodies de novo after transplantation (13). Antibodies may develop to either MHC class I antigens or MHC class II antigens (14).…”

Section: Pathogenesis Of Amrmentioning

confidence: 99%

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: Pathogenesis Of Amrmentioning

confidence: 99%

Antibody-Mediated Rejection in Lung Transplantation

Kulkarni

Bemiss²,

Hachem

2015

Curr Transpl Rep

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“…[7][8][9][10] This was further demonstrated using single antigen flow beads (SAFB) assays which greatly improved the resolution and the sensitivity of donor-specific antibodies (DSA) detection. [11][12][13][14][15][16] However, detection of serum DSA with SAFB has technical limitations, falsenegative and false-positive results being respectively caused by complement interference [17][18][19] and by anti-HLA antibodies of ill-defined pathogenic role recognizing denatured class I HLA molecules. [20][21][22][23][24][25] The presence of DSA is not synonymous with lung allograft injury.…”

Section: Introductionmentioning

confidence: 99%

Lung intragraft donor-specific antibodies as a risk factor for graft loss

Visentin

Chartier

Massara

et al. 2016

The Journal of Heart and Lung Transplantation

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“…In this model, exogenous delivery of anti-MHC class I or anti-MHC class II to the lung microenvironment induced small airway occlusion and fibrosis, creating pathologic lesions similar to those observed in humans with chronic lung graft rejection. While the Ab repertoire associated with lung graft rejection is not fully characterized, de novo anti-HLA class I and II titers, even when non-persistent, significantly predispose to chronic rejection (11, 15, 17, 19, 24–28). The alloimmune priming of HLA reactive B cells is believed to trigger loss of self-tolerance and development of cellular and humoral autoimmunity (26, 29).…”

Section: Antibodies In Ltxmentioning

confidence: 99%

“…A large body of work has established a strong humoral link that predisposes for development of BOS after LTx. DSA directed to MHC class I and II proteins, even when detected only transiently, poses significant and independent risks for BOS development and influences its onset kinetics, severity, and mortality (11, 15, 17, 19, 24–28, 71). …”

Section: Antibodies In Ltxmentioning

confidence: 99%

Autologous and Allogenous Antibodies in Lung and Islet Cell Transplantation

et al. 2016

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The field of organ transplantation has undoubtedly made great strides in recent years. Despite the advances in donor–recipient histocompatibility testing, improvement in transplantation procedures, and development of aggressive immunosuppressive regimens, graft-directed immune responses still pose a major problem to the long-term success of organ transplantation. Elicitation of immune responses detected as antibodies to mismatched donor antigens (alloantibodies) and tissue-restricted self-antigens (autoantibodies) are two major risk factors for the development of graft rejection that ultimately lead to graft failure. In this review, we describe current understanding on genesis and pathogenesis of antibodies in two important clinical scenarios: lung transplantation and transplantation of islet of Langerhans. It is evident that when compared to any other clinical solid organ or cellular transplant, lung and islet transplants are more susceptible to rejection by combination of allo- and autoimmune responses.

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De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation

Cited by 148 publications

References 24 publications

Antibody-Mediated Rejection in Lung Transplantation

Antibody-Mediated Rejection in Lung Transplantation

Lung intragraft donor-specific antibodies as a risk factor for graft loss

Autologous and Allogenous Antibodies in Lung and Islet Cell Transplantation

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