TY - JOUR
T1 - Immunopathogenesis of Behçet's disease and treatment modalities
AU - van der Houwen, T. B.
AU - van Hagen, P. M.
AU - van Laar, J. A.M.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/2
Y1 - 2022/2
N2 - Introduction: Behçet's disease (BD) is an auto-inflammatory disease, primarily characterized by recurrent painful mucocutaneous ulcerations. Methods: A literature search was performed to write a narrative review into the pathogenesis and current treatment options of BD. Results: The pathogenesis of BD remains to be elucidated, but is considered a genetically primed disease in which an external trigger causes immune activation resulting in inflammatory symptoms. GWAS data show an association between multiple genetic polymorphisms (HLA-B51, ERAP1, IL10 and IL23R-IL12RB2) and increased susceptibility to BD. Bacteria as streptococci, an unbalanced microbiome or molecular mimicry trigger the inflammation in BD. Increased production or responsiveness of pro-inflammatory components of the innate immune response (TLR, neutrophils, NK-cells or γδ T-cells) to these triggers may be a crucial step in the pathogenesis of BD. Additionally to an increased autoinflammatory response there is evidence of a dysregulated adaptive immune system, with a disturbed Th1/Th2 balance, expansion of Th17 cells and possibly a decrease in regulatory T cells, resulting in a surplus in pro-inflammatory cytokines. The inflammation causes a typical clinical phenotype including orogenital ulcerations, uveitis and skin lesions. Treatment is aimed at the aberrations found in the innate (neutrophils and γδ-T cells) and adaptive immune system (TNF-α, INF-γ, IL-1), directed at organ involvement and individualized based on patient characteristics. Conclusion: We presented an extensive review into the pathogenesis and treatment options of BD.
AB - Introduction: Behçet's disease (BD) is an auto-inflammatory disease, primarily characterized by recurrent painful mucocutaneous ulcerations. Methods: A literature search was performed to write a narrative review into the pathogenesis and current treatment options of BD. Results: The pathogenesis of BD remains to be elucidated, but is considered a genetically primed disease in which an external trigger causes immune activation resulting in inflammatory symptoms. GWAS data show an association between multiple genetic polymorphisms (HLA-B51, ERAP1, IL10 and IL23R-IL12RB2) and increased susceptibility to BD. Bacteria as streptococci, an unbalanced microbiome or molecular mimicry trigger the inflammation in BD. Increased production or responsiveness of pro-inflammatory components of the innate immune response (TLR, neutrophils, NK-cells or γδ T-cells) to these triggers may be a crucial step in the pathogenesis of BD. Additionally to an increased autoinflammatory response there is evidence of a dysregulated adaptive immune system, with a disturbed Th1/Th2 balance, expansion of Th17 cells and possibly a decrease in regulatory T cells, resulting in a surplus in pro-inflammatory cytokines. The inflammation causes a typical clinical phenotype including orogenital ulcerations, uveitis and skin lesions. Treatment is aimed at the aberrations found in the innate (neutrophils and γδ-T cells) and adaptive immune system (TNF-α, INF-γ, IL-1), directed at organ involvement and individualized based on patient characteristics. Conclusion: We presented an extensive review into the pathogenesis and treatment options of BD.
UR - http://www.scopus.com/inward/record.url?scp=85123166086&partnerID=8YFLogxK
U2 - 10.1016/j.semarthrit.2022.151956
DO - 10.1016/j.semarthrit.2022.151956
M3 - Review article
C2 - 35038644
AN - SCOPUS:85123166086
SN - 0049-0172
VL - 52
JO - Seminars in Arthritis and Rheumatism
JF - Seminars in Arthritis and Rheumatism
M1 - 151956
ER -