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

Author(s)

Lin-Wang, Hui Tzu ^[1] ; Cipullo, Reginaldo ^[2] ; Dias Franca, Joao Italo ^[3] ; Finger, Marco Aurelio ^[2] ; Rossi Neto, Joao Manoel ^[2] ; Correia, Edileide de Barros ^[2] ; Dinkhuysen, Jarbas Jackson ^[2] ; Hirata, Mario Hiroyuki ^{[4, 1]}

Affiliation

^[1] Dante Pazzanese Inst Cardiol, Lab Mol Invest Cardiol, Sao Paulo - Brazil

^[2] Dante Pazzanese Inst Cardiol, Dept Heart Transplantat, Sao Paulo - Brazil

^[3] Dante Pazzanese Inst Cardiol, Stat & Epidemiol Lab, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo - Brazil

• Document type: Journal article
• Source: Clinical Transplantation; v. 32, n. 10 OCT 2018.
• Web of Science Citations: 0

Abstract

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. MethodsResultsIn 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. We observed a higher prevalence of severe vasculitis in the early period of post-transplant, and recovery was observed to take place around 1year 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. ConclusionThe vasculitis associated with the presence of C4d and the change in intragraft gene expression profile may contribute to poor allograft outcomes. (AU)

• FAPESP's process: 12/03605-8 - Sequential study of gene expression profile in paraffin embedded endomyocardial biopsies: association with humoral rejection and cardiac allograft vasculopathy
• Grantee: Jarbas Jakson Dinkhuysen
• Support Opportunities: Regular Research Grants