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Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective

  • Conference paper
Immune Responses to Biosurfaces

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 865))

Abstract

The humoral barrier in transplant biology is the result of preformed donor-specific antibodies (DSAs), directed either against human leukocyte antigens (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term “sensitization” applies to patients carrying these antibodies. Transplantation is widely accepted as a life-saving opportunity for patients with terminal end-organ disease. However, in sensitized patients, transplant outcome is hampered by antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore, sensitized patients have limited access to “matched” organs from the both living and deceased donor pool.

Considering the crucial role of the complement system in the pathophysiology of AMR and the availability of complement intervention therapeutics, there is a growing interest in complement-targeting strategies. This review highlights the emerging importance of monitoring and modulation of the complement system in the context of enabling transplantation across humoral incompatibility in sensitized recipients with preformed anti-HLA or natural anti-ABO antibodies. It also discusses the significance of the complement system in the induction of accommodation and further emphasizes current and future perspectives of novel complement therapeutics.

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Acknowledgments

We thank Dr. Deborah McClellan for excellent editorial assistance. This work was supported by grant 2013-65X-05647-34-4 from the Swedish Research Council (VR), the European Community’s Seventh Framework Programme under the grant agreement n°602699 (DIREKT), the Kidney Foundation (Swedish Association of Kidney Patients), the Eriksson and Bergholm foundations, and faculty grants from the Linnaeus University.

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Authors and Affiliations

  1. Surgical Science, Department of Transplantation, Uppsala University Hospital, Uppsala University, Uppsala, Sweden

    Ali-Reza Biglarnia

  2. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Kristina N. Ekdahl & Bo Nilsson

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  1. Ali-Reza Biglarnia
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  2. Kristina N. Ekdahl
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  3. Bo Nilsson
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Correspondence to Ali-Reza Biglarnia .

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Editors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    John D. Lambris

  2. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Kristina N. Ekdahl

  3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Daniel Ricklin

  4. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Bo Nilsson

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Biglarnia, AR., Ekdahl, K.N., Nilsson, B. (2015). Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective. In: Lambris, J., Ekdahl, K., Ricklin, D., Nilsson, B. (eds) Immune Responses to Biosurfaces. Advances in Experimental Medicine and Biology, vol 865. Springer, Cham. https://doi.org/10.1007/978-3-319-18603-0_13

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