A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.
BACKGROUND
Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite.


METHODS
Cerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and <or=5 WBC/microL) and 79 from stage 2 (trypanosomes in CSF and/or >5 WBC/microL) patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays.


RESULTS
CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity.


CONCLUSIONS
This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.
Hainard
Alexandre
A
Biomedical Proteomics Research Group, Medical University Centre, Geneva, Switzerland.
Tiberti
Natalia
N
Robin
Xavier
X
Lejon
Veerle
V
Ngoyi
Dieudonné Mumba
DM
Matovu
Enock
E
Enyaru
John Charles
JC
Fouda
Catherine
C
Ndung'u
Joseph Mathu
JM
Lisacek
Frédérique
F
Müller
Markus
M
Turck
Natacha
N
Sanchez
Jean-Charles
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D054357:Chemokine CXCL10 / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D014347:Trypanosoma brucei gambiense / Q000302:isolation & purification; D014353:Trypanosomiasis, African / Q000175:diagnosis* / Q000473:pathology*; D055815:Young Adult
D015415:Biomarkers; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054357:Chemokine CXCL10; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D018836:Inflammation Mediators; D016209:Interleukin-8