Mixed cellular and antibody-mediated rejection in heart transplantation: In-depth pathologic and clinical observations

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• 作者：Abdallah G. Kfoury ; MD ; FACC^a ; ^b ; ^e ; ^{akfoury@imail.org" class="auth_mail" title="E-mail the corresponding author} ; Dylan V. Miller ; MD^a ; ^b ; ^e ; Greg L. Snow ; PhD^a ; Kia Afshar ; MD^a ; ^e ; Josef Stehlik ; MD^b ; ^c ; ^e ; Stavros G. Drakos ; MD ; PhD^b ; ^e ; Deborah Budge ; MD^a ; ^e ; James C. Fang ; MD^b ; ^e ; M. Patricia Revelo ; MD^b ; ^e ; Rami A. Alharethi ; MD^a ; ^e ; Edward M. Gilbert ; MD^b ; ^e ; William T. Caine ; MD^a ; ^e ; Stephen McKellar ; MD^b ; ^e ; Kimberly M. Molina ; MD^d ; ^e ; M. Elizabeth H. Hammond ; MD^a ; ^b ; ^e
• 关键词：mixed rejection ; cellular rejection ; antibody-mediated rejection ; heart transplantation ; pathology ; clinical
• 刊名：Journal of Heart and Lung Transplantation
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：35
• 期：3
• 页码：335-341
• 全文大小：1626 K

文摘

Little is known about mixed cellular and antibody-mediated rejection (MR) in heart transplantation. It remains unclear whether cardiac MR has distinctive pathologic and clinical features beyond those of simultaneous cellular rejection (CR) and antibody-mediated rejection (AMR). In this study we systematically explore the pathologic and clinical characteristics of MR in heart transplantation.

Methods

The UTAH Cardiac Transplant Program database was queried for transplant recipients who survived long enough to have at least one endomyocardial biopsy (EMB) between 1985 and 2014. Only EMBs with both CR and AMR scores documented were included. In addition to detailed pathologic analyses, we also examined the incidence and prevalence of MR, the likelihood to transition from and to MR, and mortality associated with MR.

Results

Patients (n = 1,207) with a total of 28,484 EMBs met the study inclusion criteria. The overall prevalence of MR was 7.8% and it was nearly twice as frequent within the first year post-transplant. Mild MR was by far the most common occurrence and was typically preceded by an immune active state. When CR increased in severity, AMR tended to follow, but the reverse was not true. On pathology, individual features of CR and AMR were more easily separated in cases of mild MR, whereas they substantially overlapped in more severe cases. MR was associated with a significant cardiovascular death risk that was incremental with severity.

Conclusions

MR is not common, usually occurs early after transplant, and is associated with worse outcomes. MR reflects a complex interplay between cellular and humoral processes, which varies with rejection severity.