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- Berglund, Erik, et al.
(author)
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Clinical Significance of Alloantibodies in Hand Transplantation : A Multicenter Study
- 2019
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In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 103:10, s. 2173-2182
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Journal article (peer-reviewed)abstract
- Background. Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. Methods. We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. Results. Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. Conclusions. While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.
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| 2. |
- Ulker, Pinar, et al.
(author)
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LDOES ischemic preconditioning increase flap survival by ADORA2B receptor activation?
- 2020
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In: Clinical hemorheology and microcirculation. - 1875-8622. ; 75:2, s. 151-162
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Journal article (peer-reviewed)abstract
- Ischemic preconditioning (IPC) is defined as raising tolerance to subsequent ischemic stress by exposing tissues to sub-lethal ischemia. Although many candidates have been suggested, recent studies have clearly demonstrated that adenosine-mediated ADORA2B receptor (ADORA2BR) activation is the main mechanism involved in IPC. While the tissue-protective role of this mechanism has been demonstrated in different ischemia/reperfusion (I/R) models, its role in flap surgery-derived I/R damage has not to date been investigated.To investigate the role of adenosine and ADORA2BR activation in IPC-mediated tissue protection in an epigastric flap model.Animals were divided into five main groups, all of which were then divided into two subgroups depending on whether or not they were exposed to IPC before the I/R procedure, which consisted of 6 hours of ischemia and 6 days of reperfusion. No drugs were administered in Group 1 (the control group). Animals in Group 2 were pretreated with CD73-inhibitor before IPC application or the ischemic period. Animals in Group 3 were pretreated with adenosine. Animals in Group 4 were pretreated with an ADORA2BR antagonist, and those in Group 5 with an ADORA2BR agonist. After 6 days of reperfusion, tissue survival was evaluated via histological and macroscopic analysis.IPC application significantly enhanced CD73 expressions and adenosine concentrations (p<0.01). Flap survivals were increased by IPC in Group 1 (p<0.05). However, CD73 inhibition blocked this increase (Group 2). In Group 3, adenosine improved flap survival even in the absence of IPC (p<0.01). While an ADORA2BR antagonist attenuated the tissue-protective effect of IPC (p<0.01), the ADORA2BR agonist improved flap survival by mimicking IPC in groups 4 and 5.These results provide pharmacological evidence for a contribution of CD73 enzyme-dependent adenosine generation and signaling through ADORA2BR to IPC-mediated tissue protection. They also suggest for the first time that ADORA2BR agonists may be used as a potential preventive therapy against I/R injury in flap surgeries.
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