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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-08082023-153244
Document
Author
Full name
Silvia Vidal Campos
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Teixeira, Lisete Ribeiro (President)
Camargo, Luis Fernando Aranha
Strabelli, Tânia Mara Varejão
Teixeira, Ricardo Henrique de Oliveira Braga
Title in Portuguese
Dosagem de interferon-gama na avaliação da imunidade celular específica para o citomegalovirus em receptores de transplante pulmonar
Keywords in Portuguese
Antigenemia
Citomegalovírus
Ganciclovir
Imunidade celular
Interferons
Profilaxia
Reação em cadeia de polimerase
Transplante de pulmão
Abstract in Portuguese
A infecção pelo Citomegalovirus (CMV) é importante complicação em receptores de transplante pulmonar (TxP) com impacto clínico por efeitos virais diretos e indiretos associados com rejeição celular aguda e evolução para disfunção crônica do enxerto (CLAD). Portanto, a profilaxia antiviral universal ainda é recomendada para esta população por 6 a 12 meses. Monitorar a resposta imune-específica para CMV após TxP, pode individualizar riscos de adoecimento e estabelecer melhores estratégias de prevenção antiviral. O objetivo deste estudo foi avaliar a dinâmica da reconstituição imune de células T CMV-específicas ao longo do primeiro ano após TxP e sob profilaxia antiviral universal intermitente com Ganciclovir através do teste de QuantiFeron®-CMV. Neste estudo observacional prospectivo, foram incluídos 38 pacientes transplantados de pulmão entre dezembro de 2015 e dezembro de 2016. Nos dias 45, 90 e 365 dias pós-TxP, 60%, 72% e 81%, respectivamente, dos pacientes apresentavam testes reativos para QuantiFeron®-CMV. Onze pacientes evoluíram com CMV-doença e 27 com DNAemia/CMV-infecção. Os testes reativos conseguiram predizer doença por CMV ao final da profilaxia (p=0.043), mas não no 6omês pós-transplante (p=0.148). Pontos de corte para início do tratamento antiviral para CMV-doença foram definidos para antigenemia pp65 (>= 8 células/300.000 neutrófilos; sensibilidade 62% especificidade 99% valor preditivo positivo (VPP) 89% e valor preditivo negativo (VPN) 99%) e para PCR quantitativo (>= 2610 UI/ml; sensibilidade 69% especificidade 99% VPP 90% e VPN 94%). QuantiFeron®-CMV pode auxiliar na estratificação de risco de CMV-doença pós-TxP e direcionar tempo de profilaxia antiviral individualizada
Title in English
Interferon-gamma measuring for the evaluation of specific cellular immunity to cytomegalovirus in lung transplant recipients
Keywords in English
Antigenemia
Celular immunity
Cytomegalovirus
Ganciclovir
Interferons
Lung transplantation
Polimerase chain reaction
Prophylaxis
Abstract in English
Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality among lung transplant (LTx) recipients. CMV can cause tissue-invasive disease and is associated with indirect effects such as acute allograft rejection episodes and development of chronic lung allograft dysfunction (CLAD). Thus, universal antiviral prophylaxis is preferred in most lung transplant centers. Monitoring CMV-specific immune response after LTx can individualize CMV-infection or disease risks and establish a better antiviral approach. The aim of this study was to evaluate the dynamics of immune reconstitution of CMV-specific T cells over the first year after LTx with Ganciclovir intermittent universal antiviral prophylaxis, using the QuantiFeron®-CMV test. In this prospective observational study, 38 LTx patients were enrolled between December 2015 and December 2016. On days 45, 90 and 365 days post-LTx, 60%, 72% and 81%, respectively, of the patients had QuantiFeron®-CMV reactive tests. Eleven patients presented CMV-disease and 27 DNAemia/CMV-infection. Reactive tests were able to predict CMV disease at the end of prophylaxis (p=0.043) but not at 6 months post-LTx (p=0.148). Cutoff values to initiate antiviral treatment for CMV-disease were defined for pp65 antigenemia (>= 8 cells/300,000 neutrophils; sensitivity 62% specificity 99% positive predictive value (PPV) 89% and negative predictive value (NPV) 99%) and for quantitative PCR (>= 2610 IU/ml; sensitivity 69% specificity 99% PPV 90% and NPV 94%). QuantiFeron®-CMV may help to stratify CMV-disease risk and individualized antiviral prophylaxis after LTx
 
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Publishing Date
2023-08-15
 
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