دورية أكاديمية
Rapid desensitization through immunoadsorption during cardiopulmonary bypass. A novel method to facilitate human leukocyte antigen incompatible heart transplantation.
العنوان: | Rapid desensitization through immunoadsorption during cardiopulmonary bypass. A novel method to facilitate human leukocyte antigen incompatible heart transplantation. |
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المؤلفون: | Issitt RW; Perfusion Department, Great Ormond Street Hospital for Children, London, UK.; Institute of Cardiovascular Science, University College London, London, UK.; Digital Research, Informatics and Virtual Environment, NIHR Great Ormond Street Biomedical Research Centre, London, UK., Cudworth E; Clinical Transplantation Laboratory, Barts Health NHS Trust, London, UK., Cortina-Borja M; Population, Policy and Practice Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK., Gupta A; Clinical Transplantation Laboratory, Barts Health NHS Trust, London, UK., Kallon D; Clinical Transplantation Laboratory, Barts Health NHS Trust, London, UK., Crook R; Perfusion Department, Great Ormond Street Hospital for Children, London, UK., Shaw M; Perfusion Department, Great Ormond Street Hospital for Children, London, UK., Robertson A; Perfusion Department, Great Ormond Street Hospital for Children, London, UK., Tsang VT; Institute of Cardiovascular Science, University College London, London, UK.; Department of Cardiothoracic Surgery, Great Ormond Street Hospital for Children, London, UK., Henwood S; Department of Cardiothoracic Transplantation, Great Ormond Street Hospital for Children, London, UK., Muthurangu V; Institute of Cardiovascular Science, University College London, London, UK., Sebire NJ; Digital Research, Informatics and Virtual Environment, NIHR Great Ormond Street Biomedical Research Centre, London, UK., Burch M; Institute of Cardiovascular Science, University College London, London, UK.; Department of Cardiothoracic Transplantation, Great Ormond Street Hospital for Children, London, UK.; Department of Paediatric Cardiology, Institute of Child Health, University College London, London, UK., Fenton M; Department of Cardiothoracic Transplantation, Great Ormond Street Hospital for Children, London, UK.; Department of Paediatric Cardiology, Institute of Child Health, University College London, London, UK. |
المصدر: | Perfusion [Perfusion] 2024 Apr; Vol. 39 (3), pp. 543-554. Date of Electronic Publication: 2023 Jan 10. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: SAGE Publications Country of Publication: England NLM ID: 8700166 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-111X (Electronic) Linking ISSN: 02676591 NLM ISO Abbreviation: Perfusion Subsets: MEDLINE |
أسماء مطبوعة: | Publication: London : SAGE Publications Original Publication: [London] : Edward Arnold, [c1986- |
مواضيع طبية MeSH: | Kidney Transplantation* , Heart Transplantation*, Child ; Humans ; Cardiopulmonary Bypass ; Tissue Donors ; HLA Antigens |
مستخلص: | Background: Anti-human leukocyte antigen (HLA)-antibody production represents a major barrier to heart transplantation, limiting recipient compatibility with potential donors and increasing the risk of complications with poor waiting-list outcomes. Currently there is no consensus to when desensitization should take place, and through what mechanism, meaning that sensitized patients must wait for a compatible donor for many months, if not years. We aimed to determine if intraoperative immunoadsorption could provide a potential desensitization methodology. Methods: Anti-HLA antibody-containing whole blood was added to a Cardiopulmonary bypass (CPB) circuit set up to mimic a 20 kg patient undergoing heart transplantation. Plasma was separated and diverted to a standalone, secondary immunoadsorption system, with antibody-depleted plasma returned to the CPB circuit. Samples for anti-HLA antibody definition were taken at baseline, when combined with the CPB prime (on bypass), and then every 20 min for the duration of treatment (total 180 min). Results: A reduction in individual allele median fluorescence intensity (MFI) to below clinically relevant levels (<1000 MFI), and in the majority of cases below the lower positive detection limit (<500 MFI), even in alleles with a baseline MFI >4000 was demonstrated. Reduction occurred in all cases within 120 min, demonstrating efficacy in a time period usual for heart transplantation. Flowcytometric crossmatching of suitable pseudo-donor lymphocytes demonstrated a change from T cell and B cell positive channel shifts to negative, demonstrating a reduction in binding capacity. Conclusions: Intraoperative immunoadsorption in an ex vivo setting demonstrates clinically relevant reductions in anti-HLA antibodies within the normal timeframe for heart transplantation. This method represents a potential desensitization technique that could enable sensitized children to accept a donor organ earlier, even in the presence of donor-specific anti-HLA antibodies. Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. |
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معلومات مُعتمدة: | FS/19/52/34563 United Kingdom BHF_ British Heart Foundation |
فهرسة مساهمة: | Keywords: cardiopulmonary bypass; human leukocyte antigen; immunoadsorption; paediatric; transplantation |
المشرفين على المادة: | 0 (HLA Antigens) |
تواريخ الأحداث: | Date Created: 20230110 Date Completed: 20240318 Latest Revision: 20240318 |
رمز التحديث: | 20240318 |
مُعرف محوري في PubMed: | PMC10943618 |
DOI: | 10.1177/02676591221151035 |
PMID: | 36625378 |
قاعدة البيانات: | MEDLINE |
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