Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

Proteína antiinflamatória anexina 1: mecanismos celulares e relevância clínica / Anti-inflammatory protein annexin 1: cellular mechanisms and clinical relevance

Um dos eventos de importância no processo inflamatório é o recrutamento dos leucócitos da circulação sanguínea para os sítios da inflamação por meio de interações com as células endoteliais das vênulas pós-capilares. O mecanismo de recrutamento é desencadeado por uma série de mediadores pró-inflamatórios quesão produzidos por células como mastócitos, macrófagos, células endoteliais ativadas, bem como leucócitos transmigrados para o tecido inflamado. Por outro lado, a resposta inflamatória é controlada pela ação de mediadores antiinflamatórios que atuam para manter a homeostasia da resposta imunológica e prevenir alesão tecidual. Entre esses mediadores destaca-se a anexina 1, primeiro membro descrito de uma família de proteínas ligantes de fosfolipídios dependentes de cálcio, com seqüências de aminoácidos altamente conservadas nos vertebrados. Esta proteína atua como um potente modulador endógeno da inflamação,inibindo a atividade de enzimas que atuam na produção de mediadores pró-inflamatórios e interferindo no processo de transmigração dos leucócitos. Nesta revisão, a estrutura, a expressão, os mecanismos de açãoe os efeitos farmacológicos da anexina 1 em diferentes modelos experimentais são abordados. O objetivo final das investigações é avaliar a adequação do uso da anexina 1 como um agente terapêutico eficaz no tratamento de patologias causadas pela inflamação, como a artrite reumatóide, lesão do miocárdio por isquemia-reperfusão, neoplasias e asma, por exemplo.

An overview of the effects of annexin 1 on cells involved in the inflammatory process

The concept of anti-inflammation is currently evolving with the definition of several endogenous inhibitory circuits that are important in the control of the host inflammatory response. Here we focus on one of these pathways, the annexin 1 (ANXA1) system. Originally identified as a 37 kDa glucocorticoid-inducible protein, ANXA1 has emerged over the last decade as an important endogenous modulator of inflammation. We review the pharmacological effects of ANXA1 on cell types involved in inflammation, from blood-borne leukocytes to resident cells. This review reveals that there is scope for more research, since most of the studies have so far focused on the effects of the protein and its peptido-mimetics on neutrophil recruitment and activation. However, many other cells central to inflammation, e.g. endothelial cells or mast cells, also express ANXA1: it is foreseen that a better definition of the role(s) of the endogenous protein in these cells will open the way to further pharmacological studies. We propose that a more systematic analysis of ANXA1 physio-pharmacology in cells involved in the host inflammatory reaction could aid in the design of novel anti-inflammatory therapeutics based on this endogenous mediator.