Association of FCN2 polymorphisms and Ficolin-2 levels with dengue fever in Vietnamese patients

Giang, Ngo Truong; Tong, Hoang Van; Nghia, Trinh Huu; Hung, Hoang Vu; Anh, Do Tuan; Nam, Le Van; Mao, Can Van; Giang, Nguyen Truong; Thanh, Le Dinh; Sơn, Hồ Anh; Velavan, Thirumalaisamy P.; Đỗ, Quyết; Toàn, Nguyễn Lĩnh

doi:10.1016/j.ijid.2020.02.029

Cited by 10 publications

(10 citation statements)

References 32 publications

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“…The mechanisms that led to severe clinical manifestations of dengue are not fully elucidated. Host immune responses and virus serotypes contribute to disease progression and severity (9,21). The occurrence of dengue without warning signs (DWS-), dengue with warning signs (DWS+), and SD are thought to be the result of a complex interplay between DENV and host immune factors (15).…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory Cytokines Are Modulated in Vietnamese Patients with Dengue Fever

et al. 2020

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The clinical outcome of dengue is due to a complex interplay between dengue virus (DENV) and host immune factors, including complement and cytokine systems. Proinflammatory cytokines are mainly produced by monocytes in response to infectious pathogens. This study investigated the levels of proinflammatory cytokines, including tumor necrosis factor-a (TNF-a), interleukin-1 beta (IL-1b), and IL-12 in Vietnamese patients with dengue, and their correlations with the clinical outcome of dengue infection in 156 patients clinically classified as dengue without warning signs (DWS-, n = 87), dengue with warning signs (DWS+, n = 62), and severe dengue (SD, n = 7) patients as well as in 60 healthy controls (HCs). Serum TNF-a, IL-1b, and IL-12 levels were quantified by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-a, IL-1b, and IL-12 levels were significantly increased in dengue patients compared with HCs (p < 0.0001). TNF-a levels were significantly correlated with white blood cells and platelet counts (r s = 0.52, 0.2; p < 0.0001, p = 0.018, respectively). IL-1b levels were correlated with red blood cells counts and the levels of aspartate aminotransferase and alanine aminotransferase (r s = 0.23, 0.21, 0.23; p = 0.004, 0.012, 0.005, respectively). The results suggest that these three proinflammatory cytokines are associated with the clinical outcome of dengue and could play roles in the pathogenesis of the disease.

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Section: Introductionmentioning

confidence: 99%

Proinflammatory Cytokines Are Modulated in Vietnamese Patients with Dengue Fever

et al. 2020

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“…Dengue is a serious health problem in tropical and subtropical areas including Vietnam. Studies have shown that the pathogenesis and severity of the disease are closely associated with distinct host immune responses against DENV, including components of the complement system 22,23 . Here we show that MBL2 polymorphisms and the levels of the complement proteins C2, C4b, C5, C5a, C9, factor D and factor I are associated with DENV infection and severity of the disease.…”

Section: Discussionmentioning

confidence: 99%

Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity

Giang

Tong

Đỗ

et al. 2020

Sci Rep

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The complement system may be crucial during dengue virus infection and progression to severe dengue. This study investigates the role of MBL2 genetic variants and levels of MBL in serum and complement proteins in Vietnamese dengue patients. MBL2 genotypes (− 550L/H, MBL2 codon 54), MBL2 diplotypes (XA/XO, YA/XO) and MBL2 haplotypes (LXPB, HXPA, XO) were associated with dengue in the study population. The levels of complement factors C2, C5, and C5a were higher in dengue and dengue with warning signs (DWS) patients compared to those in healthy controls, while factor D levels were decreased in dengue and DWS patients compared to the levels determined in healthy controls. C2 and C5a levels were associated with the levels of AST and ALT and with WBC counts. C9 levels were negatively correlated with ALT levels and WBC counts, and factor D levels were associated with AST and ALT levels and with platelet counts. In conclusions, MBL2 polymorphisms are associated with dengue in the Vietnamese study population. The levels of the complement proteins C2, C4b, C5, C5a, C9, factor D and factor I are modulated in dengue patients during the clinical course of dengue.

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“…These PRRs and MASPs are predominantly expressed in the liver, a major target organ affected by DENV [ 53 , 54 ]. Of note, among these PRRs, MBL and ficolin-2 have been the most widely studied in infectious diseases such as dengue [ 55 , 56 , 57 ]. A schematic diagram of the LP is presented in Figure 1 .…”

Section: Lectin Pathway In Denguementioning

confidence: 99%

“…In addition to MBL, other PRRs may have roles in dengue. Recently, the association of ficolin-2 levels, along with FCN2 polymorphisms in dengue illness, has been examined [ 55 ]. The upregulation of ficolin-2 levels during disease progression correlates with DENV infections but not with other febrile diseases of unknown origins (despite lower levels in the blood of severe cases) [ 55 ].…”

Section: Lectin Pathway In Denguementioning

confidence: 99%

“…Recently, the association of ficolin-2 levels, along with FCN2 polymorphisms in dengue illness, has been examined [ 55 ]. The upregulation of ficolin-2 levels during disease progression correlates with DENV infections but not with other febrile diseases of unknown origins (despite lower levels in the blood of severe cases) [ 55 ]. Increased ficolin-2 is probably regulated by FCN2 polymorphisms located in intron 7 (+6031A/G and +6220T/G) and exon 8 (+6424G/T; alanine to serine at codon 258), which might influence the pathogen-binding capacity and concentration ( Table 2 and Table 3 and Figure 3 ) [ 86 , 97 ].…”

Section: Lectin Pathway In Denguementioning

confidence: 99%

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Dengue and the Lectin Pathway of the Complement System

Kraivong

Punyadee

Liszewski

et al. 2021

Viruses

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Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system’s lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern recognition receptor (PRR) binding efficiency. The important PRR, mannan binding lectin (MBL), mediates DENV neutralization through (1) a complement activation-independent mechanism via direct MBL glycan recognition, thereby inhibiting DENV attachment to host target cells, or (2) a complement activation-dependent mechanism following the attachment of complement opsonins C3b and C4b to virion surfaces. The serum concentrations of lectin PRRs and their polymorphisms influence these LP activities. Conversely, to escape the LP attack and enhance the infectivity, DENV utilizes the secreted form of nonstructural protein 1 (sNS1) to counteract the MBL effects, thereby increasing viral survival and dissemination.

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Association of FCN2 polymorphisms and Ficolin-2 levels with dengue fever in Vietnamese patients

Cited by 10 publications

References 32 publications

Proinflammatory Cytokines Are Modulated in Vietnamese Patients with Dengue Fever

Proinflammatory Cytokines Are Modulated in Vietnamese Patients with Dengue Fever

Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity

Dengue and the Lectin Pathway of the Complement System

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