Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease

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.

A vital role for complement in heart disease

“…Polymorphisms in the MBL2 gene with subsequent low levels of MBL increase the risk for Chagas disease, hence confirming that the lectin pathway has a protective role (Weitzel et al, 2012). Lower levels of plasma ficolin-2 have been observed in patients with Chagas disease than in controls (Luz et al, 2013). The T cruzi parasites may induce microvesicles from blood cells, and these microvesicles form a complex on the T cruzi surface with the C3 convertase, the crucial common complement activation step, protecting the T cruzi from complement attack (Cestari et al, 2012).…”

Mannose-binding Lectin (MBL) as a susceptible host factor influencing Indian Visceral Leishmaniasis

“…In addition, three non-synonymous [18]. Lectin complement proteins have been associated with many infectious diseases including intra and extracellular infections [22][23][24][25]. Our earlier study has shown that, another analogous lectin complement protein ficolin-2 was associated with occurrence of VL [26].…”

Differential ability to resist to complement lysis and invade host cells mediated by MBL in R4 and 860 strains of Trypanosoma cruzi

“…Other components of the lectin pathway were also shown to be associated with susceptibility to CD and disease outcome. Lower L‐ficolin levels, correlated to 258S variant, were associated with CD susceptibility and severity of the disease [14]. Furthermore, MASP2 ∗ CD genotypes resulting in low MASP‐2 levels were related to increased risk of chagasic cardiomyopathy.…”