title: Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis.
abstract: BACKGROUND
  A successful host immune response to infection is dependent upon both innate and adaptive immune effector mechanisms. Cutaneous leishmaniasis results in an adaptive Th1 CD4(+) T cell response that efficiently clears the parasite, but may also result in scaring. However the role of innate mechanisms during parasite clearance remains less well defined.
  
  
  METHODS
  We examined a unique cohort of individuals, living in a Leishmania major endemic region, that were stratified among 3 distinct clinical groups in a cross-sectional study. Specifically, patients were classified either as healed (n = 17), asymptomatic (23), or naïve to infection (18) based upon the classical Leishmanin Skin Test (LST) and the presence or absence of scars. Utilizing a multiplexed immunoassay approach we characterized the induced cytokine and chemokine response to L. major.
  
  
  RESULTS
  A subset of innate immune molecules was induced in all groups. By contrast, T cell-associated cytokines were largely induced in exposed groups as compared to L. major-infection naïve individuals. Two exceptions were IL-17A and IL-12p70, induced and not induced, respectively, in naïve individuals. In addition, GM-CSF was more strongly induced in healed patients as compared to the other two groups. Surprisingly an IL-13 response was the best cytokine for classifying previously infected donors.
  
  
  CONCLUSIONS
  Exploratory data analysis, utilizing principle component analysis (PCA), revealed distinct patient clusters of the healed and naïve groups based on the most differentially induced proteins. Asymptomatic previously infected individuals were more difficult to assign to a particular cluster based on these induced proteins. Analysis of these proteins may enable the identification of biomarkers associated with disease, leading to a better understanding of the protective mechanisms of immune response against leishmaniasis.
authors.affiliation: Laboratory of Medical Parasitology, Biotechnologies and Biomolecules, Institut Pasteur de Tunis, Tunis, Tunisia.|University of Tunis El Manar, Tunis, 1068, Tunisia.
authors.forename: Wafa
authors.initials: W
authors.lastname: Kammoun-Rebai
authors.affiliation: University of Tunis El Manar, Tunis, 1068, Tunisia.|Laboratory of Transmission Control and Immunobiology of Infection, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Ikbel
authors.initials: I
authors.lastname: Naouar
authors.affiliation: Center for Human Immunology, Institut Pasteur, Paris, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Libri
authors.affiliation: Center for Human Immunology, Institut Pasteur, Paris, France.|Department of Immunology, Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France.|Inserm U818, Paris, France.
authors.forename: Matthew
authors.initials: M
authors.lastname: Albert
authors.affiliation: University of Tunis El Manar, Tunis, 1068, Tunisia.|Laboratory of Transmission Control and Immunobiology of Infection, Institut Pasteur de Tunis, Tunis, Tunisia.|Faculty of Medicine, Tunis, Tunisia.
authors.forename: Hechmi
authors.initials: H
authors.lastname: Louzir
authors.affiliation: Laboratory of Medical Parasitology, Biotechnologies and Biomolecules, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Meddeb-Garnaoui
authors.affiliation: Center for Human Immunology, Institut Pasteur, Paris, France. darragh.duffy@pasteur.fr.|Department of Immunology, Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France. darragh.duffy@pasteur.fr.|Inserm U818, Paris, France. darragh.duffy@pasteur.fr.
authors.forename: Darragh
authors.initials: D
authors.lastname: Duffy
mesh_terms: D000293:Adolescent; D000953:Antigens, Protozoan / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D007118:Immunoassay; D018793:Interleukin-13 / Q000032:analysis; D020381:Interleukin-17 / Q000032:analysis; D018320:Leishmania major / Q000302:isolation & purification / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000175:diagnosis* / Q000469:parasitology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D025341:Principal Component Analysis; D012680:Sensitivity and Specificity; D012882:Skin Tests
chemical_list: D000953:Antigens, Protozoan; D015415:Biomarkers; D016207:Cytokines; D018793:Interleukin-13; D020381:Interleukin-17; C032127:leishmanin
keywords: Asymptomatic infection; Leishmaniasis; Protein biomarkers