{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:16:07Z","timestamp":1792062967410,"version":"4.4.0"},"reference-count":64,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FOC"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p>\u2713 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.<\/jats:p>\n                  <jats:p>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 \u201carthritogenic peptide\u201d 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.<\/jats:p>","DOI":"10.3171\/foc\/2008\/24\/1\/e2","type":"journal-article","created":{"date-parts":[[2008,1,14]],"date-time":"2008-01-14T13:27:37Z","timestamp":1200317257000},"page":"E2","source":"Crossref","is-referenced-by-count":74,"title":["A review of the pathogenesis of ankylosing spondylitis"],"prefix":"10.3171","volume":"24","author":[{"given":"Elias","family":"Dakwar","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaypal","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando L.","family":"Vale","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan S.","family":"Uribe","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of South Florida, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-0240002","series-title":"Arthritis Rheum","first-page":"892","article-title":"HLA-B27-restricted CD8+ T cell response to cartilage-derived self peptides in ankylosing spondylitis","volume":"52","author":"Atagunduz","year":"2005"},{"key":"b2-0240002","series-title":"J Rheumatol","first-page":"631","article-title":"HLA-B27 testing in ankylosing spondylitis: an analysis of the pretesting assumptions","volume":"16","author":"Baron","year":"1989"},{"key":"b3-0240002","series-title":"Lancet","first-page":"904","article-title":"Ankylosing spondylitis and HL-A 27","volume":"1","author":"Brewerton","year":"1973"},{"key":"b4-0240002","series-title":"Arthritis Rheum","first-page":"1823","article-title":"Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment","volume":"40","author":"Brown","year":"1997"},{"key":"b5-0240002","series-title":"Mol Med ToDay","first-page":"224","article-title":"HLA-B27 misfolding: a solution to the spondyloarthropathy conundrum?","volume":"6","author":"Colbert","year":"2000"},{"key":"b6-0240002","series-title":"J Clin Invest","first-page":"47","article-title":"CD8(+) T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis","volume":"106","author":"Fiorillo","year":"2000"},{"key":"b7-0240002","series-title":"J Biol Chem","first-page":"2962","article-title":"Allele-dependent similarity between viral and self-peptide presentation by HLA-B27 subtypes","volume":"280","author":"Fiorillo","year":"2005"},{"key":"b8-0240002","series-title":"Ann Rheum Dis","first-page":"359","article-title":"Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Tromso, northern Norway","volume":"44","author":"Gran","year":"1985"},{"key":"b9-0240002","series-title":"J Rheumatol","first-page":"2159","article-title":"Clues to pathogenesis of spondyloarthropathy derived from synovial fluid mononuclear cell gene expression profiles","volume":"29","author":"Gu","year":"2002"},{"key":"b10-0240002","series-title":"Cell","first-page":"1099","article-title":"Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders","volume":"63","author":"Hammer","year":"1990"},{"key":"b11-0240002","series-title":"Lancet","first-page":"646","article-title":"HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis","volume":"342","author":"Hermann","year":"1993"},{"key":"b12-0240002","series-title":"Infect Immun","first-page":"120","article-title":"A patient-derived cytotoxic T-lymphocyte clone and two peptide-dependent monoclonal antibodies recognize HLA-B27-peptide complexes with low stringency for peptide sequences","volume":"64","author":"Huang","year":"1996"},{"key":"b13-0240002","series-title":"Arthritis Rheum","first-page":"381","article-title":"Occurrence of ankylosing spondylitis in a nationwide series of twins","volume":"38","author":"J\u00e4rvinen","year":"1995"},{"key":"b14-0240002","series-title":"J Clin Invest","first-page":"2746","article-title":"HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27\/ human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m","volume":"98","author":"Khare","year":"1996"},{"key":"b15-0240002","series-title":"Rheum Dis Clin North Am","first-page":"883","article-title":"Animal models of human leukocyte antigen B27-linked arthritides","volume":"24","author":"Khare","year":"1998"},{"key":"b16-0240002","series-title":"Arthritis Rheum","first-page":"778","article-title":"Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States","volume":"41","author":"Lawrence","year":"1998"},{"key":"b17-0240002","series-title":"Nature","first-page":"321","article-title":"The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation","volume":"353","author":"Madden","year":"1991"},{"key":"b18-0240002","series-title":"Cell","first-page":"1035","article-title":"The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC","volume":"70","author":"Madden","year":"1992"},{"key":"b19-0240002","series-title":"Curr Opin Rheumatol","first-page":"337","article-title":"Anterior uveitis: current concepts of pathogenesis and interactions with the spondyloarthropathies","volume":"14","author":"Martin","year":"2002"},{"key":"b20-0240002","series-title":"Tissue Antigens","first-page":"299","article-title":"Conserved TCR beta chain usage in reactive arthritis; evidence for selection by a putative HLA-B27-associated autoantigen","volume":"60","author":"May","year":"2002"},{"key":"b21-0240002","series-title":"Lancet","first-page":"1137","article-title":"Classification of inflammatory arthritis by enthesitis","volume":"352","author":"McGonagle","year":"1998"},{"key":"b22-0240002","series-title":"J Immunol","first-page":"6665","article-title":"Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies","volume":"163","author":"Mear","year":"1999"},{"key":"b23-0240002","series-title":"J Rheumatol","first-page":"2120","article-title":"Frequency of atlantoaxial subluxation and neurologic involvement in patients with ankylosing spondylitis","volume":"22","author":"Ramos-Remus","year":"1995"},{"key":"b24-0240002","series-title":"Curr Opin Rheumatol","first-page":"332","article-title":"The genetic basis of ankylosing spondylitis","volume":"18","author":"Reveille","year":"2006"},{"key":"b25-0240002","series-title":"Clin Rheumatol","first-page":"224","article-title":"Cauda equina syndrome in ankylosing spondylitis: a case report and review of the literature","volume":"14","author":"Sant","year":"1995"},{"key":"b26-0240002","series-title":"Best Pract Res Clin Rheumatol","first-page":"571","article-title":"Pathogenesis of ankylosing spondylitis: current concepts","volume":"20","author":"Smith","year":"2006"},{"key":"b27-0240002","series-title":"J Immunol","first-page":"4168","article-title":"Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression","volume":"150","author":"Taurog","year":"1993"},{"key":"b28-0240002","series-title":"J Exp Med","first-page":"2359","article-title":"The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats","volume":"180","author":"Taurog","year":"1994"},{"key":"b29-0240002","series-title":"J Immunol","first-page":"2438","article-title":"HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response","volume":"175","author":"Turner","year":"2005"},{"key":"b30-0240002","series-title":"Arthritis Rheum","first-page":"361","article-title":"Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria","volume":"27","author":"van der Linden","year":"1984"},{"key":"b31-0240002","series-title":"J Rheumatol","first-page":"1981","article-title":"Clinical vertebral fractures in patients with ankylosing spondylitis","volume":"31","author":"Vosse","year":"2004"},{"key":"b32-0240002","series-title":"Arthritis Rheum","first-page":"1672","article-title":"Association of HLA-B39 with HLA-B27-negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in Japanese patients. Evidence for a role of the peptide-anchoring B pocket","volume":"38","author":"Yamaguchi","year":"1995"},{"key":"b1-0240002","series-title":"Arthritis Rheum","first-page":"892","article-title":"HLA-B27-restricted CD8+ T cell response to cartilage-derived self peptides in ankylosing spondylitis","volume":"52","author":"Atagunduz","year":"2005"},{"key":"b2-0240002","series-title":"J Rheumatol","first-page":"631","article-title":"HLA-B27 testing in ankylosing spondylitis: an analysis of the pretesting assumptions","volume":"16","author":"Baron","year":"1989"},{"key":"b3-0240002","series-title":"Lancet","first-page":"904","article-title":"Ankylosing spondylitis and HL-A 27","volume":"1","author":"Brewerton","year":"1973"},{"key":"b4-0240002","series-title":"Arthritis Rheum","first-page":"1823","article-title":"Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment","volume":"40","author":"Brown","year":"1997"},{"key":"b5-0240002","series-title":"Mol Med ToDay","first-page":"224","article-title":"HLA-B27 misfolding: a solution to the spondyloarthropathy conundrum?","volume":"6","author":"Colbert","year":"2000"},{"key":"b6-0240002","series-title":"J Clin Invest","first-page":"47","article-title":"CD8(+) T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis","volume":"106","author":"Fiorillo","year":"2000"},{"key":"b7-0240002","series-title":"J Biol Chem","first-page":"2962","article-title":"Allele-dependent similarity between viral and self-peptide presentation by HLA-B27 subtypes","volume":"280","author":"Fiorillo","year":"2005"},{"key":"b8-0240002","series-title":"Ann Rheum Dis","first-page":"359","article-title":"Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Tromso, northern Norway","volume":"44","author":"Gran","year":"1985"},{"key":"b9-0240002","series-title":"J Rheumatol","first-page":"2159","article-title":"Clues to pathogenesis of spondyloarthropathy derived from synovial fluid mononuclear cell gene expression profiles","volume":"29","author":"Gu","year":"2002"},{"key":"b10-0240002","series-title":"Cell","first-page":"1099","article-title":"Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders","volume":"63","author":"Hammer","year":"1990"},{"key":"b11-0240002","series-title":"Lancet","first-page":"646","article-title":"HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis","volume":"342","author":"Hermann","year":"1993"},{"key":"b12-0240002","series-title":"Infect Immun","first-page":"120","article-title":"A patient-derived cytotoxic T-lymphocyte clone and two peptide-dependent monoclonal antibodies recognize HLA-B27-peptide complexes with low stringency for peptide sequences","volume":"64","author":"Huang","year":"1996"},{"key":"b13-0240002","series-title":"Arthritis Rheum","first-page":"381","article-title":"Occurrence of ankylosing spondylitis in a nationwide series of twins","volume":"38","author":"J\u00e4rvinen","year":"1995"},{"key":"b14-0240002","series-title":"J Clin Invest","first-page":"2746","article-title":"HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27\/ human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m","volume":"98","author":"Khare","year":"1996"},{"key":"b15-0240002","series-title":"Rheum Dis Clin North Am","first-page":"883","article-title":"Animal models of human leukocyte antigen B27-linked arthritides","volume":"24","author":"Khare","year":"1998"},{"key":"b16-0240002","series-title":"Arthritis Rheum","first-page":"778","article-title":"Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States","volume":"41","author":"Lawrence","year":"1998"},{"key":"b17-0240002","series-title":"Nature","first-page":"321","article-title":"The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation","volume":"353","author":"Madden","year":"1991"},{"key":"b18-0240002","series-title":"Cell","first-page":"1035","article-title":"The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC","volume":"70","author":"Madden","year":"1992"},{"key":"b19-0240002","series-title":"Curr Opin Rheumatol","first-page":"337","article-title":"Anterior uveitis: current concepts of pathogenesis and interactions with the spondyloarthropathies","volume":"14","author":"Martin","year":"2002"},{"key":"b20-0240002","series-title":"Tissue Antigens","first-page":"299","article-title":"Conserved TCR beta chain usage in reactive arthritis; evidence for selection by a putative HLA-B27-associated autoantigen","volume":"60","author":"May","year":"2002"},{"key":"b21-0240002","series-title":"Lancet","first-page":"1137","article-title":"Classification of inflammatory arthritis by enthesitis","volume":"352","author":"McGonagle","year":"1998"},{"key":"b22-0240002","series-title":"J Immunol","first-page":"6665","article-title":"Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies","volume":"163","author":"Mear","year":"1999"},{"key":"b23-0240002","series-title":"J Rheumatol","first-page":"2120","article-title":"Frequency of atlantoaxial subluxation and neurologic involvement in patients with ankylosing spondylitis","volume":"22","author":"Ramos-Remus","year":"1995"},{"key":"b24-0240002","series-title":"Curr Opin Rheumatol","first-page":"332","article-title":"The genetic basis of ankylosing spondylitis","volume":"18","author":"Reveille","year":"2006"},{"key":"b25-0240002","series-title":"Clin Rheumatol","first-page":"224","article-title":"Cauda equina syndrome in ankylosing spondylitis: a case report and review of the literature","volume":"14","author":"Sant","year":"1995"},{"key":"b26-0240002","series-title":"Best Pract Res Clin Rheumatol","first-page":"571","article-title":"Pathogenesis of ankylosing spondylitis: current concepts","volume":"20","author":"Smith","year":"2006"},{"key":"b27-0240002","series-title":"J Immunol","first-page":"4168","article-title":"Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression","volume":"150","author":"Taurog","year":"1993"},{"key":"b28-0240002","series-title":"J Exp Med","first-page":"2359","article-title":"The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats","volume":"180","author":"Taurog","year":"1994"},{"key":"b29-0240002","series-title":"J Immunol","first-page":"2438","article-title":"HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response","volume":"175","author":"Turner","year":"2005"},{"key":"b30-0240002","series-title":"Arthritis Rheum","first-page":"361","article-title":"Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria","volume":"27","author":"van der Linden","year":"1984"},{"key":"b31-0240002","series-title":"J Rheumatol","first-page":"1981","article-title":"Clinical vertebral fractures in patients with ankylosing spondylitis","volume":"31","author":"Vosse","year":"2004"},{"key":"b32-0240002","series-title":"Arthritis Rheum","first-page":"1672","article-title":"Association of HLA-B39 with HLA-B27-negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in Japanese patients. 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