The Possible Genetic and Environmental Factors Related to Behçet's Disease: Trisomy 8 and SARS-CoV-2

Behet's disease (BD) is a chronic inflammatory disorder of unknown etiology that is primarily characterized by recurrent oral ulcers, skin lesions, uveitis, and genital ulcers.It also presents with arthritis and epididymitis and, in severe cases, gastrointestinal, vascular, or central nervous system manifestations.BD is characterized by neutrophil hyperactivity (1) with predominant neutrophil infiltration at sites of acute inflammation (2).A genetic predisposition exists, with approximately 60% of patients carrying human leukocyte antigen (HLA)-B51 and 30% carrying HLA-A26 (3).BD is more prevalent in regions along the ancient Silk Road, including Japan, Central Asia, the Middle East, and the Mediterranean, and correlates with HLA-B51 across different ethnic groups.Recent studies have also identified many other genes related to inflammation and immune responses as susceptibility genes for BD (4).Environmental factors have also been suggested in BD etiology, as it is rare among Japanese descendants in Hawaii (5).Activation of the innate immune system in response to microorganisms has been implicated in the autoinflammatory mechanisms leading to BD. Ulcer sites in BD have a higher degree of Streptococcus sanguinis detection compared to healthy individuals (6).It has been hypothesized that molecular mimicry might induce autoimmunity, as the stress response protein Hsp65 of S. sanguinis shares a high amino acid sequence homology with human Hsp60 (7).In addition, some susceptibility genes identified in BD are known to be associated with infections such as leprosy ( 8).Approximately 2% of BD patients have concomitant myelodysplastic syndrome (MDS) (9), a hematologic disorder characterized by dysplastic bone marrow cells and ineffective hematopoiesis.MDS can progress to leukemia and typically initially presents with cytopenia.Immune abnormalities occur in MDS, with 10-20% of cases involving autoimmune diseases, including relapsing polychondritis,