Matrix metalloproteinase-9 and intercellular adhesion molecule 1 are powerful staging markers for human African trypanosomiasis.
OBJECTIVE
A critical step before treatment of human African trypanosomiasis (HAT) is the correct staging of the disease. As late stage is established when trypanosomes cross the blood-brain barrier and invade the central nervous system, we hypothesized that matrix metalloproteinases and cell adhesion molecules could indicate, alone or in combination, the disease progression from the first to the second stage of HAT.


METHODS
We measured the levels of MMP-2, MMP-9, ICAM-1, VCAM-1 and E-selectin in the cerebrospinal fluid (CSF) of 63 Trypanosoma brucei gambiense-infected patients (15 stage 1 and 48 stage 2). Staging was based on counting of white blood cells (WBC) and/or parasite detection in CSF. Concentrations were obtained either by ELISA or multiplex bead suspension assays, and results were compared with three known HAT staging markers (CXCL10, CXCL8 and H-FABP).


RESULTS
ICAM-1 and MMP-9 accurately discriminated between stage 1 and stage 2 patients with HAT with 95% sensitivity (SE) for 100% specificity (SP), which was better than CXCL10 (93% SE for 100% SP), one of the most promising known markers. Combination of ICAM-1 and MMP-9 with H-FABP provided a panel that resulted in 100% of SE and SP for staging HAT.


CONCLUSIONS
ICAM-1 and MMP-9, alone or in combination, appeared as powerful CSF staging markers of HAT. Final validation of all newly discovered staging markers on a large multi-centric cohort including both forms of the disease as well as patients with others infections should be performed.
Biomedical Proteomics Research Group, Medical University Centre, Geneva, Switzerland.
Alexandre
A
Hainard
Natalia
N
Tiberti
Xavier
X
Robin
Dieudonné M
DM
Ngoyi
Enock
E
Matovu
John C K
JC
Enyaru
Markus
M
Müller
Natacha
N
Turck
Joseph M
JM
Ndung'u
Veerle
V
Lejon
Jean-Charles
JC
Sanchez
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015815:Cell Adhesion Molecules / Q000134:cerebrospinal fluid; D020808:Central Nervous System Protozoal Infections / Q000134:cerebrospinal fluid; D018925:Chemokines / Q000134:cerebrospinal fluid; D018450:Disease Progression; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000134:cerebrospinal fluid*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D014347:Trypanosoma brucei gambiense / Q000302:isolation & purification; D014353:Trypanosomiasis, African / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D055815:Young Adult
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018925:Chemokines; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9