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.
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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.
To use high-density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).
Ankylosing spondylitis (AS), psoriasis and inflammatory bowel disease (IBD) often coexist in the same patient and in their families. In AS, genes within the MHC region, in particular HLA‑B27, account for nearly 25% of disease hereditability, with additional small contributions from genes outside of the MHC locus, including those involved in intracellular antigen processing (that is, ERAP1, which interacts with HLA‑B27) and cytokine genes such as those involved in the IL‑17–IL‑23 pathway. Similar to AS, the strongest genetic signal of susceptibility to psoriasis and psoriatic arthritis also emanates from the MHC region (attributable mostly to HLA‑C*06:02 although other genes have been implicated), and gene–gene interaction of HLA‑C with ERAP1. The remaining hereditary load is from genes involved in cytokine production, specifically genes in the IL‑17–IL‑23 pathway, the NFκB pathway and the type 2 T‑helper pathway. In IBD, similar genetic influences are operative. Indeed, genes important in the regulation of the IL‑17–IL‑23 pathway and, in Crohn’s disease, genes important for autophagy (that is, NOD2 and ATG16L1 and IRGM) have a role in conferring susceptibility of individuals to these diseases. Thus, AS, psoriasis and IBD seem to share similar pathogenic mechanisms of aberrant intracellular antigen processing or elimination of intracellular bacteria and cytokine production, especially in the IL‑17–IL‑23 pathway.
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