Innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease.
BACKGROUND
We investigated the pathological and diagnostic role of selected markers of inflammation, oxidant/antioxidant status, and cellular injury in human Chagas disease.


METHODS
Seropositive/chagasic subjects characterized as clinically-symptomatic or clinically-asymptomatic (n = 116), seronegative/cardiac subjects (n = 102), and seronegative/healthy subjects (n = 45) were analyzed for peripheral blood biomarkers.


RESULTS
Seropositive/chagasic subjects exhibited an increase in sera or plasma levels of myeloperoxidase (MPO, 2.8-fold), advanced oxidation protein products (AOPP, 56%), nitrite (5.7-fold), lipid peroxides (LPO, 12-17-fold) and malondialdehyde (MDA, 4-6-fold); and a decline in superoxide dismutase (SOD, 52%) and glutathione (GSH, 75%) contents. Correlation analysis identified a significant (p<0.001) linear relationship between inflammatory markers (AOPP/nitrite: r = 0.877), inflammation and antioxidant/oxidant status (AOPP/glutathione peroxidase (GPX): r = 0.902, AOPP/GSH: r = 0.806, Nitrite/GPX: 0.773, Nitrite/LPO: 0.805, MDA/MPO: 0.718), and antioxidant/oxidant levels (GPX/MDA: r = 0.768) in chagasic subjects. Of these, MPO, LPO and nitrite biomarkers were highly specific and sensitive for distinguishing seropositive/chagasic subjects from seronegative/healthy controls (p<0.001, training and fitting AUC/ROC >0.95). The MPO (r = 0.664) and LPO (r = 0.841) levels were also correlated with clinical disease state in chagasic subjects (p<0.001). Seronegative/cardiac subjects exhibited up to 77% decline in SOD, 3-5-fold increase in LPO and glutamate pyruvate transaminase (GPT) levels, and statistically insignificant change in MPO, AOPP, MDA, GPX, GSH, and creatine kinase (CK) levels.


CONCLUSIONS
The interlinked effects of innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease. The MPO, LPO and nitrite are excellent biomarkers for diagnosing seropositive/chagasic subjects, and MPO and LPO levels have potential utility in identifying clinical severity of Chagas disease.
Department of Microbiology and Immunology, School of Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.
Monisha
M
Dhiman
Yun A
YA
Coronado
Cecilia K
CK
Vallejo
John R
JR
Petersen
Adetoun
A
Ejilemele
Sonia
S
Nuñez
Maria Paola
MP
Zago
Heidi
H
Spratt
Nisha Jain
NJ
Garg
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000032:analysis*; D015415:Biomarkers / Q000097:blood*; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D016877:Oxidants / Q000097:blood*
D000975:Antioxidants; D015415:Biomarkers; D016877:Oxidants