Fataneh Tavasolian, Robert D. Inmanabc
Spondylitis Program, Division of Rheumatology, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
Departments of Medicine and Immunology, University of Toronto, Toronto, Ontario, Canada
Published: 20th April 2021
Abstract:
“Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disability that is part of the rheumatic disease group of spondyloarthropathies. AS commonly influences the joints of the axial skeleton. The contributions to AS pathogenesis of genetic susceptibility (particularly HLA-B27 and ERAP-1) and epigenetic modifications, like non-coding RNAs, as well as environmental factors, have been investigated over the last few years.
But the fundamental etiology of AS remains elusive to date. The evidence summarized here indicates that in the immunopathogenesis of AS, microRNAs and the gut microbiome perform critical functions.
We discuss significant advances in the immunological mechanisms underlying AS and address potential cross-talk between the gut microbiome and host microRNAs. This critical interaction implicates a co-evolutionary symbiotic link between host immunity and the gut microbiome.”
Snippets:
“AS is regarded as an autoimmune disease, in part because of autoantibodies detected in AS [1] but also because the strong association with MHC implicates a disruption in adaptive immune homeostasis.
AS is typically involves the sacroiliac joints, spine, and peripheral joints, commonly before the age of 45 years [2,3]. Inflammation primarily targets entheses where immune cells, especially lymphoid cells, localize and enhance local secretion of IL-17, TNF-α, IFN-γ, and other cytokines…
AS has a major genetic predisposition and has the highest association with HLA among all rheumatic diseases. Different subtypes of HLAsingle bondB27, including B∗2702, B∗2704, B∗2705, have been reported as raising the chance of developing AS. The differential risk associated with B27 subtypes was apparent as these subtypes with slight amino acid alterations lead to changed HLA heavy chain conformation and altered peptide presentation.
The pathogenic function of HLAsingle bondB27, however, remains an open question…
Epigenetic processes including DNA methylation, histone modifications, and non-coding RNA are thought to be critical in the interaction between the disease and the environment when determining the genetic basis of the disease.
AS is a prime example of the importance of the contribution of epigenetics to polygenic disease susceptibility, as is implicated in other autoimmune and inflammatory-mediated disorders. miRNAs represent a group of regulating RNAs that behave as gene expression key…
The gut microbiota is a comprehensive multi-species community of bacteria, fungi, archaea, and protozoa, and is populated by more cells and genes of greater diversity than their mammalian hosts.
Initial colonization of the host mammalian mucosal surfaces in the infancy performs a critical function in the growth and development of the human immune response. Most key aspects in host immunity education which actually occur during the first years of life…
Both microbiota and miRNA have important health and disease roles. Several studies have demonstrated that miRNAs influence human-microbiota interactions.
In the gut of germ-free mice that had been colonized with the microbiota of pathogen-free mice, miRNA profile variations were found compared to wild mice. This variation may affect gene expression in intestinal disorders. As a result, the host miRNA expression has close ties with the microbiota…”
Summary:
“The connection between genetic predisposition and environmental influences is of critical importance in the pathogenesis of AS.
Human epigenome-microbiome crosstalk may underlie the immune response in AS and by epigenetic alteration, dysbiosis can induce aberrant immune responses.
Communication between bacteria, host cells, and miRNAs could also regulate the degradation and stabilization of eukaryotic mRNAs in AS, which could be used as a new approach to novel therapy.”
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