1. Intragraft vasculitis and gene expression analysis: association with acute rejection and prediction of mortality in long-term heart transplantation
- Author
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Marco Aurélio Finger, Mario Hiroyuki Hirata, Reginaldo Cipullo, João Italo Dias França, Edileide de Barros Correia, João Manoel Rossi Neto, Hui Tzu Lin-Wang, and Dinkhuysen Jj
- Subjects
Graft Rejection ,Male ,Vasculitis ,Pathology ,medicine.medical_specialty ,Necrosis ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,030230 surgery ,CCL2 ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,TRANSPLANTE DE CORAÇÃO ,Risk Factors ,Biopsy ,medicine ,Humans ,Longitudinal Studies ,Retrospective Studies ,Heart transplantation ,Transplantation ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Gene Expression Profiling ,Graft Survival ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,Real-time polymerase chain reaction ,Heart Transplantation ,Female ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Follow-Up Studies - 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. 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. more...
- Published
- 2018