Laboratório de Imunopatologia Molecular-Departamento de Patologia Médica, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
PLoS One. 2013 Apr 4;8(4):e60237. doi: 10.1371/journal.pone.0060237. Print 2013.
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.
We 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).
Patients 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.
The 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.
L- ficolin（由 FCN2 编码）与包括克氏锥虫在内的许多病原体上的乙酰化糖部分结合，促进补体系统对其吞噬和裂解。
我们检测了 160 例慢性恰加斯病感染患者和 71 名健康个体的 L- ficolin 水平，并对 243 例患者的 FCN2 多态性（启动子中的 -986 G>A、-602 G>A 和 -4 A>G 以及外显子 8 中的 A258S）进行了检测，其中 88 例为不确定（无症状），96 例有心脏表现，23 例有消化表现，33 例有心脏-消化表现（其中 2 例未指明），305 例为对照组（135 例为 A258S）。
与对照组相比，患者的血浆 L- ficolin 水平较低（p<0.0001）。在不同的心脏受累组中，中度表现的个体的 L- ficolin 水平高于重度表现的个体（P=0.039）。在患者中发现较低的 L- ficolin 水平与 258S 变异有关（P=0.034）。与对照组相比，心脏患者中 -4A/G 杂合子较少（OR=0.56[95%CI=0.33-0.94]，P=0.034）。然而，杂合子 -4A/G 基因型与 258S 变异和 258SS 纯合子在心脏-消化患者中比在对照组（OR=14.1[95%CI=3.5-56.8]，P=0.0001）和不确定患者中更为常见（OR=3.2[95%CI=1.1-9.4]，P=0.037）。我们还发现与对照组相比，258S 变异的等位基因频率与心脏消化性恰加斯病有关（OR=2.24[95%CI=1.1-4.5]，P=0.037）。因此，患者 L- ficolin 水平降低不仅反映了疾病过程中蛋白的消耗，还反映了心脏症状患者中 258S 变异的更高频率。
这是第一项关于巴西队列的研究，将 L- ficolin 血浆水平和 FCN2 变异与恰加斯病及其后续疾病进展联系起来。L- ficolin 水平和 FCN2*A258S 多态性的预后价值应在其他环境中进一步评估。
