A Review of the Pathogenesis of Ankylosing Spondylitis
A Review of the Pathogenesis of Ankylosing Spondylitis
Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease involving primarily the sacroiliac joints and the axial skeleton. The main clinical features are back pain and progressive stiffness of the spine. Oligoarthritis of the hips and shoulders, enthesopathy, and anterior uveitis are common, and involvement of the heart and lungs is rare. The current understanding of the pathogenesis of this disorder is limited. Despite the strong association between human leukocyte antigen B27 (HLA-B27) and susceptibility to AS reported over the past 30 years, the exact pathogenic role of HLA-B27 in AS and other spondyloarthropathies has yet to be determined. The authors present a review of the literature pertaining to the pathogenesis of AS over the past several decades.
Ankylosing spondylitis is a polygenic disorder, with HLA-B27 playing a critical causative role in its pathogenesis. Animal studies of the immunobiology of HLA-B27 have provided significant insight into the pathogenic role of HLA-B27. The search for the antigenic peptide to support the "arthritogenic peptide" hypothesis has been disappointing. Over the past decade there has been increasing interest in the critical role of the misfolding and unfolded protein response of the heavy chain HLA-B27 in the modulation of the inflammatory response. Although there have been significant new findings in the understanding of the pathogenesis of AS, the exact mechanisms have yet to be identified. There is considerable optimism that additional susceptibility genes, predisposing factors, and regulators of the inflammatory process will be identified that will provide avenues for future treatment.
Ankylosing spondylitis is a major subtype of a group of chronic inflammatory diseases known as spondyloarthropathies. It affects young adults with the peak age of onset between 20 and 30 years. Men are more often affected than women, with a ratio of approximately 3:1. About 80% of patients with AS develop the first symptoms before their third decade of life and < 5% present in the fourth decade of life. Patients with juvenile-onset AS become symptomatic at or before 16 years of age. The prevalence of AS is 0.1-1.4%, and this is dependent on the ethnicity, the prevalence of HLA-B27, the selection of patients for evaluation, and the screening criteria used for diagnosis. This condition is more common in persons of northern European heritage and least common in sub-Saharan Africans. Although it is important to recognize the strong correlation between the prevalence of HLA-B27 and AS in any given population, one must not forget that most individuals who test positive for HLA-B27 are healthy. Non-HLA-B27 genetic and environmental factors have an important role in the development and progression of this disease.
Abstract and Introduction
Abstract
Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease involving primarily the sacroiliac joints and the axial skeleton. The main clinical features are back pain and progressive stiffness of the spine. Oligoarthritis of the hips and shoulders, enthesopathy, and anterior uveitis are common, and involvement of the heart and lungs is rare. The current understanding of the pathogenesis of this disorder is limited. Despite the strong association between human leukocyte antigen B27 (HLA-B27) and susceptibility to AS reported over the past 30 years, the exact pathogenic role of HLA-B27 in AS and other spondyloarthropathies has yet to be determined. The authors present a review of the literature pertaining to the pathogenesis of AS over the past several decades.
Ankylosing spondylitis is a polygenic disorder, with HLA-B27 playing a critical causative role in its pathogenesis. Animal studies of the immunobiology of HLA-B27 have provided significant insight into the pathogenic role of HLA-B27. The search for the antigenic peptide to support the "arthritogenic peptide" hypothesis has been disappointing. Over the past decade there has been increasing interest in the critical role of the misfolding and unfolded protein response of the heavy chain HLA-B27 in the modulation of the inflammatory response. Although there have been significant new findings in the understanding of the pathogenesis of AS, the exact mechanisms have yet to be identified. There is considerable optimism that additional susceptibility genes, predisposing factors, and regulators of the inflammatory process will be identified that will provide avenues for future treatment.
Introduction
Ankylosing spondylitis is a major subtype of a group of chronic inflammatory diseases known as spondyloarthropathies. It affects young adults with the peak age of onset between 20 and 30 years. Men are more often affected than women, with a ratio of approximately 3:1. About 80% of patients with AS develop the first symptoms before their third decade of life and < 5% present in the fourth decade of life. Patients with juvenile-onset AS become symptomatic at or before 16 years of age. The prevalence of AS is 0.1-1.4%, and this is dependent on the ethnicity, the prevalence of HLA-B27, the selection of patients for evaluation, and the screening criteria used for diagnosis. This condition is more common in persons of northern European heritage and least common in sub-Saharan Africans. Although it is important to recognize the strong correlation between the prevalence of HLA-B27 and AS in any given population, one must not forget that most individuals who test positive for HLA-B27 are healthy. Non-HLA-B27 genetic and environmental factors have an important role in the development and progression of this disease.
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