Genetics and immunodysfunction underlying Behçet’s disease and immunomodulant treatment approaches

Abstract

Behçet's disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD.

MicroRNA implications in the etiopathogenesis of ankylosing spondylitis

“…Autoimmunity refers to a pathologic condition, in which the immune system recognizes self‐antigens and tissues, which results in an immune response against an individual's own cells and tissues by different immune constituents, such as autoreactive antibodies and T cells (Azizi, Ahmadi, et al, ; Azizi, Hafezi, et al, ; Azizi, Ziaee, et al, ; Salmaninejad et al, ; Singh et al, ). Modifications in miRNA regulation appear to be highly associated with the progression of immune dysfunctions and autoimmunity.…”

Is there any association between human T-lymphotropic virus type 1 (HTLV-1) infection and Behcet’s disease?

“…A three-fold higher prevalence of HTLV-1 infection among BD patients compared to general population was observed; however, this difference was not statistically significant (P value = 0.16). BD is a chronic autoimmune disorder affecting tissues and organs of the body [20,24]. The main etiology of the disease is unknown.…”

“…ing route stretching from the Mediterranean, across the Middle East to the Far East [20,21]. Iran is located on the Silk Road and has a high prevalence of BD with an incidence of 282 persons/year over the past 20 years.…”

Behçet’s Disease: An Overview of Etiopathogenesis

“…Polymorphisms within genes encoding the cytokines may affect their function and may be associated with disease predisposition (44). Researchers identified several non-HLA genetic associations by GWAS including ERAP1, IL23 receptor (IL23R), IL-23R/IL-12RB2, IL-10 , and STAT genes (38, 45).…”

“…Alterations of TNF expression related to gene polymorphisms may be responsible for the higher cytokine activity (56, 57). Polymorphic alleles were more frequent in BD patients and were related to higher TNF production by monocytes or mononuclear cells (45, 57). Mutations in the Mediterranean fever gene were also considered additional BD susceptibility factors (45).…”