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Open Access Research article

High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis

Fabrícia Alvisi de Oliveira1, Carla Vanessa Oliveira Silva1, Nayra Prata Damascena1, Rodrigo Oliveira Passos1, Malcolm S Duthie2, Jeffrey A Guderian2, Ajay Bhatia2, Tatiana Rodrigues de Moura1, Steven G Reed2, Roque Pacheco de Almeida13 and Amélia Ribeiro de Jesus13*

Author Affiliations

1 Molecular Biology Laboratory, Hospital Universitário – Universidade Federal de Sergipe, Rua Claudio Batista s/n, Bairro Sanatório, Aracaju, Sergipe 49060-10, Brazil

2 IDRI- Infectious Disease Research Institute, Seattle, WA 98102, USA

3 Instituto de Investigação em Imunologia (iii) – Institutos Nacionais de Ciência e Tecnologia (INCT), CNPq, São Paulo, Brazil

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BMC Infectious Diseases 2013, 13:331  doi:10.1186/1471-2334-13-331

Published: 19 July 2013

Abstract

Background

Soluble CD40 ligand (sCD40L) and matrix metalloproteinase 9 (MMP-9) are inflammation markers and have been poorly described in infectious disease. In this prospective study, we describe the sera kinetics of these two molecules in the course of treatment follow up in human visceral leishmaniasis (VL).

Methods

Sera from VL patients were collected before and during follow up of regular Antimony treatment. sCD40L and MMP-9 were measured by Luminex assay. Paired analysis by Wilcoxon signed test was used for comparison of values of the same subjects before and after initiation of treatment. Correlations between clinical data and parasite load with the serum levels of sCD40L and MMP-9 were performed by Spearman test. Tests were considered statistically significant if the probability of a type I error was less than 5% (p-value < 0.05).

Results

While sCD40L and MMP-9 were not observed in sera from non endemic controls which are at low risk of Leishmania chagasi infection, elevated levels were observed in sera from VL patients, and an increase in sCD40L and MMP-9 levels were detectable during the follow-up of VL patients undergoing antimony treatment. sCD40L levels were also high in individuals living in endemic settings at high risk of infection (endemic controls). Additionally, negative correlations were found between spleen sizes and MMP-9 before treatment and sCD40L at day 15 of treatment. Negative correlations were also found between parasite load with both sCD40L and MMP-9.

Conclusion

Serum sCD40L and MMP-9 are identified as new and simple biomarkers in two situations: (i) monitoring the success of therapy and (ii) predicting favorable clinical outcome of human VL.

Keywords:
Visceral leishmaniasis; Soluble CD40 ligand; Matrix metalloproteinase-9; Biomarkers; Clinical outcome