Intragraft vasculitis and gene expression analysis: Association with acute rejection and prediction of mortality in long-term heart transplantation.

Autor: Lin-Wang HT; Laboratory of Molecular Investigation in Cardiology, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil., Cipullo R; Department of Heart Transplantation, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil., Dias França JI; Statistic and Epidemiology Laboratory, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil., Finger MA; Department of Heart Transplantation, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil., Rossi Neto JM; Department of Heart Transplantation, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil., Correia EB; Department of Heart Transplantation, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil., Dinkhuysen JJ; Department of Heart Transplantation, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil., Hirata MH; Laboratory of Molecular Investigation in Cardiology, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil.; School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Clinical transplantation [Clin Transplant] 2018 Oct; Vol. 32 (10), pp. e13373. Date of Electronic Publication: 2018 Aug 31.
DOI: 10.1111/ctr.13373
Abstrakt: Introduction: Vasculitis entails heterogeneous origins; it starts with an inflammatory process that leads to small vessels' necrosis, hemorrhage, and ischemic lesion, and may further result in occlusion of the vascular lumen. Vasculitis' contribution to allograft rejection is still unclear. This study aims to investigate the incidence of vasculitis in the early stages of heart transplantation as well as to assess the intragraft genes' expression associated with vascular function and subsequently to verify the way in which it affects the outcome of the allograft.
Methods: In this retrospective study, 300 archive paraffin-embedded endomyocardial biopsies from 63 heart allograft recipients were assessed. Cellular rejection and vasculitis were diagnosed through histological analysis, and antibody-mediated rejection was performed with immunohistochemical C4d staining. The transcripts of ICAM, VCAM, VEGF, CCL2, IFNG, TGFB, TNF, ADIPOR1, and ADIPOR2 genes were examined through quantitative polymerase chain reaction using B2M for normalization.
Results: We observed a higher prevalence of severe vasculitis in the early period of post-transplant, and recovery was observed to take place around 1 year post-transplant. Additionally, vasculitis was found to be directly associated with acute cellular rejection and antibody-mediated rejection. The intense C4d capillary positivity predicts higher long-term cardiovascular disease mortality. In comparison with the vasculitis-free group, the group with severe vasculitis displayed reduced left ventricular ejection fraction and an upregulation of VCAM and IFNG associated with the downregulation of VEGF, ADIPOR1, and ADIPOR2.
Conclusion: The vasculitis associated with the presence of C4d and the change in intragraft gene expression profile may contribute to poor allograft outcomes.
(© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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