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Spondylitis Association of America Research Article Archive

Health research has high value to society. It can provide important information about disease trends and risk factors, outcomes of treatment, functional abilities, patterns of care, and health care costs and use. The different approaches to research provide complementary insights. Clinical trials can provide important information about the efficacy and adverse effects of medical interventions by controlling the variables that could impact the results of the study, but feedback from real-world clinical experience is also crucial for comparing and improving the use of drugs, vaccines, medical devices, and diagnostics.

Below you will find links to some of the studies that have contributed to our increased understanding of spondyloarthritis.

SAA receives no government funding and relies on the generous donations from individuals to create and maintain the programs and services aimed at improving the futures of the 2.7 million Americans affected by spondylitis.

Research Article Archive

Advances in classification, basic mechanisms and clinical science in ankylosing spondylitis and axial spondyloarthritis

Philip C. Robinson and Helen Benham


The field of spondyloarthritis has seen huge advances over the past 5 years. The classification of axial disease has been redefined by the axial spondyloarthritis criteria that incorporate disease captured before radiographic damage is evident as well as established erosive sacroiliac joint disease. Our knowledge of genetics and basic immunological pathways has progressed significantly. In addition, revolutionary progress has been achieved with the availability of tumour necrosis factor inhibitors for treating patients with moderate to severe disease. In parallel a number of novel biomarkers have been identified that show significant promise for the future. Advances in magnetic resonance imaging have helped define positive disease. We have identified that T1 and short tau inversion recovery sequences are best for the diagnosis of axial spondyloarthritis and gadolinium contrast is not additive for diagnosis. Progress has been made in identifying potential agents and strategies that reduce radiographic progression. A number of referral strategies aimed at appropriate identification of patients have been trialed and found to be effective. There is still substantial work ahead but the advances of the last 5 years have made a huge and tangible difference at the clinical coalface and we suggest this trend will continue.

Developments in therapies for spondyloarthritis

Joachim Sieper


First-line therapy for spondyloarthritis (SpA) has not yet altered in the wake of new classification criteria; NSAIDs and physical therapy are recommended. Anti-TNF agents can be used when NSAIDs fail, but their efficacy has potentially been limited in previous trials by inclusion criteria requiring the presence of established, active disease. Now, not only patients with axial SpA (axSpA) with radiographic signs of sacroiliitis (that is, with ankylosing spondylitis), but also patients in whom structural damage is not—yet—visible radiographically (non-radiographic axSpA) can be included in trials of therapy for axSpA. TNF blockers, it seems already, are at least similarly effective in patients with non-radiographic axSpA as in those with established AS. Short symptom duration and a positive C‑reactive protein test at baseline are currently the best predictors for a good response to TNF-blocking agents. Biologic agents besides anti-TNF therapies have so far failed in the treatment of axSpA. New bone formation seems currently to be best prevented by NSAIDs, not by TNF blockers. Whether earlier effective treatment of bony inflammation with anti-TNF therapy will be able to prevent ossification at a later stage has yet to be determined. New classification criteria for peripheral SpA will also allow treatment trials to be conducted more systematically than has previously been possible in this subgroup of patients.

Diagnosis and classification in spondyloarthritis: identifying a chameleon

Astrid van Tubergen and Ulrich Weber


Spondyloarthritis (SpA) defines a group of interrelated diseases, including ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, enteropathic-related spondylitis and arthritis, and undifferentiated SpA. The clinical presentation of SpA is heterogeneous, and no single shared distinguishing feature exists for the conditions comprising SpA; in daily practice, diagnosis is usually made on the basis of a combination of symptoms, the findings of physical examination, imaging and laboratory investigations. Several classification criteria have been developed for AS and SpA, which are useful in a research setting but cannot be automatically applied to the diagnosis of individual patients. Currently, MRI is the most sensitive imaging modality available for detection of sacroiliitis, often enabling detection of axial inflammation long before structural lesions are observed radiographically, thus facilitating early diagnosis of axial SpA. However, MRI will never capture all facets of SpA and the expert opinion of a rheumatologist will remain the crucial step in recognition of this disease. In this Review, we discuss diagnosis and classification of AS and SpA, and highlight how MRI might facilitate both processes.

Functionally distinct ERAP1 allotype combinations distinguish individuals with Ankylosing Spondylitis

Emma Reeves, Alexandra Colebatch-Bourn, Tim Elliott, Christopher J. Edwards, and Edward James

For more than 40 y, expression of HLA-B27 has been strongly associated with the chronic inflammatory disease Ankylosing Spondylitis (AS); however, the mechanisms underlying this association are still unknown. Single nucleotide polymorphisms within the aminopeptidase endoplasmic reticulum aminopeptidase 1 (ERAP1), which is essential for trimming peptides before they are presented to T cells by major histocompatibility complex (MHC) class I molecules, have been linked with disease. We show that ERAP1 is a highly polymorphic molecule comprising allotypes of single nucleotide polymorphisms. The prevalence of specific ERAP1 allotypes is different between AS cases and controls. Both chromosomal copies of ERAP1 are codominantly expressed, and analysis of allotype pairs provided clear stratification of individuals with AS versus controls. Functional analyses demonstrated that ERAP1 allotype pairs seen in AS cases were poor at generating optimal peptide ligands for binding to murine H-2Kb and -Db and the AS-associated HLA-B*2705. We therefore provide strong evidence that polymorphic ERAP1 alters protein function predisposing an individual to AS via its influence on the antigen processing pathway.

Genetic Dissection of Acute Anterior Uveitis Reveals Similarities and Differences in Associations Observed With Ankylosing Spondylitis

Philip C. Robinson, et al.


To use high-density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).


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