Behçet’s Disease: An Overview of Etiopathogenesis

Abstract

Behçet's disease (BD) is a systemic inflammatory disease with a chronic, relapsing-remitting course of unknown etiology hallmarked predominantly by mucocutaneous lesions and ocular involvement. BD shares some common features with autoimmune and autoinflammatory diseases and spondyloarthropathies (MHC-I-opathies). It is related to more than one pathogenic pathway triggered by environmental factors such as infectious agents in genetically predisposed subjects. The interplay between genetic background and immune system is linked to the BD presentation. Genetic factors have been investigated extensively, and several recent genome-wide association studies have confirmed HLA-B * 51 to be the strongest genetic susceptibility factor. However, new non-HLA susceptibility genes have been identified. Genetic variations in the genes encoding the cytokines could affect their function and be associated with disease susceptibility. Infectious agents such as Streptococcus sanguinis or the differences in salivary or gut microbiome composition can be considered to trigger the innate-derived inflammation, which is, subsequently, sustained by adaptive immune responses. Altered trimming of microbial and/or endogenous peptides by endoplasmic reticulum aminopeptidase 1 (ERAP1), presented by HLA-B * 51 , may play a key role in BD pathogenesis causing an alteration in T cell balance with downregulation of Tregs and expansion of Th1 and Th17. The activity of neutrophils is increased and there is an intense neutrophil infiltration in the early stage of inflammation in organs affected by the disease. Association with HLA-B * 51 and increased IL-17 response seems to have an important role in neutrophil activity. In this paper, we provide an overview of the most recent advances on BD etiopathogenesis.

Is Helicobacter pylori associated with Behçet's syndrome? A meta‐analysis

“…The strongest genetic susceptibility factor for BS is located inside the MHC class I region including the human leukocyte antigen‐B51 (HLA‐B * 51) . BS‐associated gene polymorphisms were localized in molecules responding to microorganisms . The most possible mechanism of action of bacterial infections including H pylori in the pathogenesis of BS may involve molecular homology of bacterial antigens and heat‐shock proteins (HSP), which is now proposed as the possible antigen in BS .…”

“…19 BS-associated gene polymorphisms were localized in molecules responding to microorganisms. 1 The most possible mechanism of action of bacterial infections including H pylori in the pathogenesis of BS may involve molecular homology of bacterial antigens and heat-shock proteins (HSP), which is now proposed as the possible antigen in BS. 20,21 Infectious agents trigger the innate-derived inflammation, which can be subsequently sustained by adaptive immune responses.…”

“…1 The disease is most commonly distributed along the ancient silk route but has been reported from almost all continents. 1,2 Its etiology remains unknown. Genetic, environmental, and immunological factors are suggested to be implicated in the development of BS.…”

Differential urine proteome analysis of a bovine IRBP induced uveitis rat model by discovery and parallel reaction monitoring proteomics

“…Differential proteins in these GO terms include Protein S100-A8, Neutrophil antibiotic peptide NP-4, Isocitrate dehydrogenase 1 (NADP+), Annexin A2, Ras-related protein Rap-1A, Transforming protein RhoA, Heat shock protein HSP 90-alpha, Carcinoembryonic antigen-related cell adhesion molecule 1 and Glucose-6-phosphate isomerase. The activity of neutrophils is increased and there is an intense neutrophil infiltration in the early stage of inflammation in uveitis [32,33]. Acute inflammatory response, innate immune response and inflammatory response were significantly enriched at day 5 and 8.…”

Uveitis bei Behçet-Syndrom in Deutschland – Prognose unter aktueller Therapie

“…Der stärkste genetische Faktor für das Behçet-Syndrom ist in der MHC-Klasse-I-Region (MHC: Haupthistokompatibilitätskomplex) lokalisiert und betrifft das Humane Leukozytenantigen-B51 (HLA-B51) [5]. Darüber hinaus finden genomweite Studien eine Assoziation mit Polymorphismen in den Genen, die verschiedene Zytokine wie Interleukin-10 (IL-10), Interleukin-23-Rezeptor (IL-23R) und Endoplasmatische-Retikulum-Aminopeptidase (ERAP1) codieren [6]. Dieser genetische Polymorphismus beeinflusst die Zytokinfunktion und ist mit einer erhöhten Krankheitsprädisposition assoziiert.…”