title: High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are associated with favorable clinical evolution in human visceral leishmaniasis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Biology Laboratory, Hospital Universitário - Universidade Federal de Sergipe, Rua Claudio Batista s/n, Bairro Sanatório, Aracaju, Sergipe 49060-10, Brazil.
authors.forename: Fabrícia Alvisi
authors.initials: FA
authors.lastname: de Oliveira
authors.forename: Carla
authors.initials: C
authors.lastname: Vanessa Oliveira Silva
authors.forename: Nayra Prata
authors.initials: NP
authors.lastname: Damascena
authors.forename: Rodrigo Oliveira
authors.initials: RO
authors.lastname: Passos
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Duthie
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Guderian
authors.forename: Ajay
authors.initials: A
authors.lastname: Bhatia
authors.forename: Tatiana Rodrigues
authors.initials: TR
authors.lastname: de Moura
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Roque Pacheco
authors.initials: RP
authors.lastname: de Almeida
authors.forename: Amélia Ribeiro
authors.initials: AR
authors.lastname: de Jesus
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D019013:CD40 Antigens / Q000097:blood*; D002648:Child; D005260:Female; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000097:blood* / Q000175:diagnosis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D059208:Parasite Load; D011379:Prognosis
chemical_list: D015415:Biomarkers; D019013:CD40 Antigens; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9