Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease

Messias-Reason, Iara; Schafranski, Marcelo Derbli; Kremsner, Peter G.; Kun, Jürgen F. J.

doi:10.1111/j.1365-2249.2009.03975.x

Cited by 76 publications

(65 citation statements)

References 24 publications

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“…In Brazilian chronic RHD patients, who show prolonged time of infection or repeated streptococcal infections together with low expression levels of ficolin 2 protein, the haplotype G/G/A (-986/-602/-4) was found to be more frequent than in controls [9].…”

Section: Innate Immune Response: Tlr-2 [Toll Like Receptor 2] [8] Andmentioning

confidence: 92%

Rheumatic Heart Disease: Key Points on Valve Lesions Development

Guilherme

Köhler²,

Pommerantzeff³

et al. 2012

J Clin Exp Cardiolog

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Rheumatic heart disease lesions are mediated by inflammatory and autoimmune reactions. Several genes related to both innate and adaptive immune responses are involved in the development of the disease. Adhesion molecules and chemokines facilitate heart tissue-T cell infiltration. T lymphocytes are the major effectors of crossreactivity between streptococcal and human proteins leading to RHD. The in vitro analysis of heart-tissue infiltrating T cells showed their ability to recognize streptococcal-M protein peptides as well as self-antigens by molecular mimicry mechanism. A cytokine balance favoring Th1 polarization and production of inflammatory cytokines and few IL-4 producing cells in the valves lead to the progression and maintenance of valvular lesions.

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Section: Innate Immune Response: Tlr-2 [Toll Like Receptor 2] [8] Andmentioning

confidence: 92%

Rheumatic Heart Disease: Key Points on Valve Lesions Development

Guilherme

Köhler²,

Pommerantzeff³

et al. 2012

J Clin Exp Cardiolog

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“…Ficolins (FCN) are pattern-recognition proteins involved in innate immunity, which upon binding to their specific pathogen-associated molecular patterns on the microbial surfaces trigger the immune response either by binding to collectin cellular receptors or by initiating the complement lectin pathway. Ficolin-2 was shown to bind to lipoteichoic acid, a cell wall constituent in all Gram-positive bacteria such as Streptococcus [18]. Polymorphisms of the genes codifying the above protein were associated with RF and/or its manifestations ( Table 1).…”

Section: Genetic Contribution To Susceptibilitymentioning

confidence: 97%

Understanding rheumatic fever

2011

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Through a comprehensive review of the recent findings on rheumatic fever, we intend to propose a new physiopathologic model for this disease. A Medline search was performed for all articles containing the terms rheumatic fever or rheumatic heart disease in title or abstract from 1970 to 2011. Best evidence qualitative technique was used to select the most relevant. The scientific interest on rheumatic fever has notably diminished throughout the twentieth century as evidenced by the comparison of the proportion of articles in which RF was a subject in 1950 (0.26%) and today (0.03%) [Pubmed]. However, RF remains a major medical and social problem in the developing world and in the so-called hotspots, where it still causes around 500.000 deaths each year, not too different from the pre-antibiotic era. The role of genetic factors in RF susceptibility is discussed. Familiar aggregation, similarity of disease patterns between siblings, identical twin, and HLA correlation studies are evidence for a genetic influence on RF susceptibility. The suspect-involved genes fall mainly into those capable of immunologic mediation. Molecular mimicry explains the triggering of RF, but an intense and sustained inflammation is needed to cause sequels. Also, RF patients vary greatly in terms of symptoms. It is likely that a genetic background directing immune response towards a predominantly Th1 or Th2 pattern contributes to these features. The recent findings on rheumatic fever provide important insight on its physiopathology that helps understanding this prototype post-infectious autoimmune disease giving insights on other autoimmune conditions.

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“…Two well-conducted studies have explored the putative importance of the FCN2 polymorphisms and the possible importance in invasive pneumococcal disease in adults and self reported respiratory infections in children [65,68] , but no significant associations were observed. Rheumatic fever and chronic rheumatic heart disease has been investigated for association with promoter polymorphisms in the FCN2 gene [69] . These latter results show that the FCN2 haplotype (-986/-602 and -4 G/G/A) that is associated with the lowest ficolin-2 serum [31] is also associated with chronic rheumatic heart disease.…”

Section: Variation In Fcn Genesmentioning

confidence: 99%

The Genetics of Ficolins

et al. 2009

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Ficolins constitute a family of proteins whose biological role has been an enigma for many years. Over the past few years it has become evident that ficolins are part of the innate immune system and function as recognition molecules in the complement system. The 3 human ficolins, ficolin-1 (M-ficolin), ficolin-2 (L-ficolin) and ficolin-3 (H-ficolin or Hakata antigen) are encoded by the FCN1, FCN2 and FCN3 genes, respectively. Phylogenetic studies suggest that ficolins are of ancient origin. Ficolin-3 seems to be the most ancient molecule, from a phylogenetic perspective. Searches in databases and phylogenetic tree analysis demonstrate that the ficolin precursor has gone through an expansion involving independent duplication events in the different branches of the evolutionary tree. Of particular interest is the prediction that ficolin-1 appears to be present as an ortholog molecule. All human FCN genes are polymorphic. The FCN2 gene encoding ficolin-2, contains polymorphisms that affect ligand binding, while differences in the serum levels are associated with promoter polymorphisms. Recently, a frame-shift variation in the FCN3 gene was described, leading to ficolin-3 deficiency and defective complement activation. This FCN3 variation was also shown to be associated with immunodeficiency. This survey summarizes the current phylogenetic and inter-individual molecular understanding of the FCN genes.

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Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease

Cited by 76 publications

References 24 publications

Rheumatic Heart Disease: Key Points on Valve Lesions Development

Rheumatic Heart Disease: Key Points on Valve Lesions Development

Understanding rheumatic fever

The Genetics of Ficolins

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