Primary Ficolin-3 deficiency – Is it associated with increased susceptibility to infections?

Michalski, Mateusz; Świerzko, Anna St.; Pągowska‐Klimek, Izabela; Niemir, Zofia I.; Mazerant, Karolina; Domżalska-Popadiuk, Iwona; Moll, Maciej; Cedzyński, Maciej

doi:10.1016/j.imbio.2015.01.003

Cited by 35 publications

(24 citation statements)

References 9 publications

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“…These proteins include: PECAM-1, a cell adhesion and signaling receptor that is expressed on hematopoietic and endothelial cells that has a role in the inflammatory process 26 ; SAP, a protein found in amyloid deposits that binds to apoptotic cells and the nuclear component of necrotic cells 27 and has links with the complement system; 28 VEGF sR2, a soluble receptor involved in vascular endothelial cell development 29 ; cathepsin Z which has links with protein turnover in cells and tumor progression 30 ; the GHR, that mediates the actions of growth hormone which promotes cell division, regeneration and growth 31 ; ficolin-3, a protein that is related to the complement system 32 and mediates the clearance of apoptotic cells, 33 and leptin, an adipocyte-derived hormone linked with obesity and preeclampsia. 34 In contrast, other proteins were lower in cases of PTB compared with term controls and included: JAG1, a protein linked with the notch signaling pathway, 35 MMP-2, a metalloproteinase involved in the breakdown of extracellular matrix that has links with tumor progression 36 notch-3, shown to have a role in fetal-maternal communication during implantation and placentation, 37 and, angiopoietin-2, which has a role in the regulation of endothelial cell survival and vascular maturation.…”

Section: Methodsmentioning

confidence: 99%

The relationship of circulating proteins in early pregnancy with preterm birth

Lynch

Wagner

Deterding

et al. 2016

American Journal of Obstetrics and Gynecology

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BACKGROUND Preterm birth (PTB) (<37 completed weeks gestation) is a pathological outcome of pregnancy and a major global health problem. Babies born preterm have an elevated risk for long term adverse medical and neurodevelopmental sequelae. Substantial evidence implicates intrauterine infection and/or inflammation in PTB. However, these are often relatively late findings in the process, when PTB is inevitable. Identification of earlier markers of PTB may make successful intervention possible. Although select proteins, notably, those related to the inflammatory pathways, have been associated with PTB, there has been a lack of research into the role of other protein pathways in the development of PTB. The purpose of this study was to investigate, using a previously described biomarker discovery approach, a subset of circulating proteins and their association with PTB focusing on samples from early pregnancy. OBJECTIVES 1) To perform a large-scale biomarker discovery, utilizing an innovative platform to identify proteins associated with preterm birth in plasma taken between 10 and 15 weeks’ gestation and, 2) To determine which protein pathways are most strongly associated with preterm birth. To address these aims we measured 1129 proteins in a plasma sample from early pregnancy using a multiplexed aptamer–based proteomic technology developed in Colorado by SomaLogic. STUDY DESIGN Using a nested case-control approach, we measured proteins at a single time point in early pregnancy in 41 women who subsequently delivered preterm and 88 women who had term uncomplicated deliveries. We measured 1129 proteins using a multiplexed aptamer–based proteomic technology developed by SomaLogic. Logistic regressions and random forests were used to compare protein levels. RESULTS The complement factors B and H and the coagulation factors IX and IX ab were the highest ranking proteins distinguishing cases of preterm birth from term controls. The top 3 pathways associated with preterm birth were the complement cascade, the immune system and the clotting cascade. CONCLUSIONS Using a discovery approach, these data provide further confirmation that there is an association of immune and coagulation–related events in early pregnancy with preterm birth. Thus, plasma protein profiles at 10–15 weeks of gestation are related to the development of preterm birth later in pregnancy.

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Section: Methodsmentioning

confidence: 99%

The relationship of circulating proteins in early pregnancy with preterm birth

Lynch

Wagner

Deterding

et al. 2016

American Journal of Obstetrics and Gynecology

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“…107 A few cases of ficolin-3 deficiency have been reported to date. 140 We reported the first patient with ficolin-3 deficiency: A 32-year-old male homozygous for a frameshift mutation (1637delC) in exon 5 of FCN3 (rs28357092). 141 The frameshift mutation results in an altered amino acid composition is unknown which aspects of the clinical phenotype that relate to the mutation in WASP alone and which parts that relate to the frameshift variant in FCN3.…”

Section: Genetic Variations and Their Association With Diseasementioning

confidence: 99%

“…Only a few variations in FCN3 have been detected and these are present in low frequencies . A few cases of ficolin‐3 deficiency have been reported to date . We reported the first patient with ficolin‐3 deficiency: A 32‐year‐old male homozygous for a frameshift mutation (1637delC) in exon 5 of FCN3 (rs28357092) .…”

Section: The Ficolinsmentioning

confidence: 99%

A journey through the lectin pathway of complement—MBL and beyond

Garred

Genster

Pilely

et al. 2016

Immunological Reviews

311

302

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Mannose-binding lectin (MBL), collectin-10, collectin-11, and the ficolins (ficolin-1, ficolin-2, and ficolin-3) are soluble pattern recognition molecules in the lectin complement pathway. These proteins act as mediators of host defense and participate in maintenance of tissue homeostasis. They bind to conserved pathogen-specific structures and altered self-antigens and form complexes with the pentraxins to modulate innate immune functions. All molecules exhibit distinct expression in different tissue compartments, but all are found to a varying degree in the circulation. A common feature of these molecules is their ability to interact with a set of serine proteases named MASPs (MASP-1, MASP-2, and MASP-3). MASP-1 and -2 trigger the activation of the lectin pathway and MASP-3 may be involved in the activation of the alternative pathway of complement. Furthermore, MASPs mediate processes related to coagulation, bradykinin release, and endothelial and platelet activation. Variant alleles affecting expression and structure of the proteins have been associated with a variety of infectious and non-infectious diseases, most commonly as disease modifiers. Notably, the severe 3MC (Malpuech, Michels, Mingarelli, and Carnevale) embryonic development syndrome originates from rare mutations affecting either collectin-11 or MASP-3, indicating a broader functionality of the complement system than previously anticipated. This review summarizes the characteristics of the molecules in the lectin pathway.

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“…FLC3 deficiency is a rare disease of major scientific and clinical interest because heterozygous carriers have 50% reduction in circulating ficolin-3 levels. To date, only one case of cardiac disease has been described in an 11-month-old male infant who was operated on to repair a congenital heart defect [115]. Finally, the possibility exists that patients with genetic disease are more susceptible to RF [116].…”

Section: Familial Susceptibilitymentioning

confidence: 99%