Mannose-Binding Lectin 2 (MBL2) combined genotypes deficiency is associated with susceptibility for Oral Lichen Planus

Abstract

Oral Lichen Planus (OLP) is an oral inflammatory condition, mediated by host immune system reaction, presenting basal membrane damages with inflammatory lesions in the mouth and/or skin. In this study, the role of functional polymorphisms in the MBL2 gene, encoding for Mannose-Binding Protein C (MBP-C), a member of the innate immune response and an acute-phase protein able to activate the complement cascade, was investigated to assess a possible association with OLP susceptibility in Italian patients. Two variations at the promoter region (called H/L and X/Y) and three at the first exon (at codon 52, 54, and 57) of the MBL2 gene were analyzed in 69 OLP patients and 244 healthy controls from northeastern Italy. Considering the polymorphisms singularly, the MBL2 X allele and C/T genotype of the D allele (correlated with low MBP-C expression) were associated with susceptibility to develop OLP. Moreover, when taking into account MBL2 combined genotypes, more OLP patients were deficient MBP-C producers than not deficient, who were more represented among healthy controls. MBL2 combined genotypes, responsible for deficient MBP-C production, are associated with an increased risk of developing OLP.

Mannan‐binding lectin exacerbates the severity of psoriasis by promoting plasmacytoid dendritic cell differentiation via the signal transducer and activator of transcription 3–interferon regulatory factor 8 axis

“…However, it seems that MBL has dual effects in the regulation of skin inflammation. On the one hand, decreased MBL levels resulting from variant MBL2 polymorphisms are responsible for the progression of dermatomyositis and oral lichen planus, which might be attributed to the impaired clearance of apoptotic cells in the skin 17,19,20,25 . On the other hand, MBL exacerbated cutaneous burn injury and ischemia/reperfusion injury by facilitating inflammatory responses 34,35 .…”

“…Mannan‐binding lectin (MBL, also known as mannose‐binding lectin), a vital component of the complement system, plays a crucial role in innate immune defense and the inflammatory response 16 . MBL is encoded by the gene MBL2, and polymorphisms of the promoter region or exon 1 in MBL2 affect the serum level of MBL 17 . It has been studied that the MBL2 polymorphism is relevant to several skin diseases, such as dermatomyositis, lichen planus, and Behçet’s disease 17–19 .…”

“…MBL is encoded by the gene MBL2, and polymorphisms of the promoter region or exon 1 in MBL2 affect the serum level of MBL 17 . It has been studied that the MBL2 polymorphism is relevant to several skin diseases, such as dermatomyositis, lichen planus, and Behçet’s disease 17–19 . MBL is synthesized predominantly in the liver and circulates into blood but is also deposited on the lesional skin of systemic lupus erythematosus (SLE) and pemphigus 20–22 .…”

Oral lichen planus: a microbiologist point of view

“…In the same year, Zhou and Vieira ( 2018 ) carried out a meta-analysis of the disease and reported a positive association between a tumor necrosis factor-alpha polymorphism, a G to A transitional mutation at nucleotide -308, and the development of OLP. The following year, Polesello et al ( 2019 ) reported that functional polymorphisms of the MBL2 gene, affecting either the promoter or the first exon (codons 52, 54 and 57), reduced expression of the protein and correlated with an increased risk of developing OLP; MBL2, mannose-binding lectin, is a trimeric protein with the ability to activate the complement pathway. Contrastingly, polymorphisms such as those occurring on the programmed cell death protein 1, that once were thought to be associated with OLP, have been recently shown to have no effect on the disease (Ghapanchi et al 2019 ).…”

A Plausible Role for Collectins in Skin Immune Homeostasis

“…MBL promotes keratinocyte production of chemokine (C-X-C motif) ligand 1 and enhances neutrophil infiltration in psoriatic lesions ( 6 ). Genotypes associated with low MBL production lead to high susceptibility to oral lichen planus ( 60 ). MBL2 polymorphism has been linked with Behçet’s disease, cellulitis, and ulcerations ( 40 ).…”