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Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
2015 (English)In: IMMUNE RESPONSES TO BIOSURFACES: MECHANISMS AND THERAPEUTIC INTERVENTIONS, 2015, 211-233 p.Conference paper, Published paper (Refereed)
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. 211-233 p.
Series
Advances in Experimental Medicine and Biology, ISSN 0065-2598 ; 865
Keyword [en]
ABO- and HLA-incompatibility, Antibody-mediated rejection, Terminal complement inhibition, Transplantation, Complement therapeutics, Desensitization
National Category
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-265645DOI: 10.1007/978-3-319-18603-0_13ISI: 000361838300014PubMedID: 26306452ISBN: 978-3-319-18603-0 (print)ISBN: 978-3-319-18602-3 (print)OAI: oai:DiVA.org:uu-265645DiVA: diva2:866428
Conference
1st International Conference on Immune Response to Biosurfaces, SEP 27-OCT 02, 2014, Chania, GREECE
Funder
Swedish Research Council, 2013-65X-05647-34-4EU, FP7, Seventh Framework Programme, 602699
Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2015-11-05Bibliographically approved

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Biglarnia, Ali-RezaNilsson, Kristina EkdahlNilsson, Bo

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