Abstract
BackgroundL-ficolin (encoded by FCN2) binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system.MethodsWe investigated L-ficolin levels in 160 T. cruzi infected patients with chronic Chagas disease and 71 healthy individuals, and FCN2 polymorphisms (−986 G>A, −602 G>A, and −4 A>G in the promoter and A258S in exon 8) in 243 patients, being 88 indeterminate (asymptomatic), 96 with cardiac, 23 with digestive and 33 with cardiodigestive manifestations (two were unspecified) and 305 controls (135 for A258S).ResultsPatients presented lower L-ficolin plasma levels than controls (p<0.0001). Among the different groups of cardiac commitment, individuals with moderate forms had higher L-ficolin levels than the severe forms (P = 0.039). Lower L-ficolin levels were found associated with the 258S variant in the patients (P = 0.034). We found less −4A/G heterozygotes in the cardiac patients, than in the controls (OR = 0.56 [95% CI = 0.33–0.94], P = 0.034). Heterozygote −4A/G genotypes with the 258S variant and 258SS homozygotes were nevertheless more frequent among cardiodigestive patients than in controls (OR = 14.1 [95% CI = 3.5–56.8], P = 0.0001) and in indeterminate patients (OR = 3.2 [95% CI = 1.1–9.4], P = 0.037). We also found an association of the allelic frequency of the 258S variant with cardiodigestive Chagas disease compared to controls (OR = 2.24 [95% CI = 1.1–4.5], P = 0.037). Thus, decreased patient levels of L-ficolin reflect not only protein consumption due to the disease process, but also the higher frequency of the 258S variant in patients with cardiodigestive symptoms.ConclusionThe very first study on Brazilian cohort associates both L-ficolin plasma levels and FCN2 variants to Chagas disease and subsequent disease progression. The prognostic value of L-ficolin levels and the FCN2*A258S polymorphism should be further evaluated in other settings.
Highlights
Chagas disease (CD) occurs in 18 different countries, mostly throughout South and Central America, and affects approximately 15 million people worldwide [1]
In this study we aim to evaluate whether L-ficolin levels and FCN2 polymorphisms could be possible prognostic markers for susceptibility to the different clinical forms of CD
L-ficolin levels were higher in the group with 45 to years of age, compared with those aged above years
Summary
Chagas disease (CD) occurs in 18 different countries, mostly throughout South and Central America, and affects approximately 15 million people worldwide [1]. Despite the fact that approximately 50% of the individuals infected by T. cruzi stay in the indeterminate or asymptomatic form throughout their lives, which in general present good prognosis, each year about 2–5% of them progress to symptomatic forms of the disease, presenting irreversible cardiac and/or digestive and/or disorders [2]. A plausible presumption is that individuals who remain asymptomatic are able to reduce parasite numbers in the early phase of infection, and down modulate the immune response, limiting the development of pathology. Ficolins are pattern-recognition proteins which bind to specific pathogen-associated molecular patterns (PAMP) on microorganism surfaces, promoting activation of the complement cascade through the lectin pathway thereby triggering the innate immune response [9]. L-ficolin (encoded by FCN2) binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system
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