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Advances in managing ankylosing spondylitis.

ABSTRACT: Ankylosing spondylitis (AS) is a chronic inflammatory disease with prominent involvement of the spine and sacroiliac joints which frequently leads to significant spine deformity and disability. The development of effective therapies for AS, particularly with anti-tumor necrosis factor agents, has resulted in improved symptoms and functions for many patients, and clinical research increasingly suggests that effective therapy can also prevent destruction in the spine and other structures. Recent focus of disease classification in AS has emphasized that many individuals with features of inflammatory back pain but no visible changes on plain x-rays have active inflammatory disease when imaged with magnetic resonance imaging (MRI). Recent studies indicate that individuals with "non-radiographic" spondylitis can also respond to anti-inflammatory therapies. Several new agents are also showing promise for treatment of AS. These developments represent a significant advance in the management of this debilitating condition.

SUBMITTER: Daikh DI

PROVIDER: S-EPMC4166936 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Advances in managing ankylosing spondylitis.

Daikh David I DI Chen Patty P PP

F1000prime reports 20140904

Ankylosing spondylitis (AS) is a chronic inflammatory disease with prominent involvement of the spine and sacroiliac joints which frequently leads to significant spine deformity and disability. The development of effective therapies for AS, particularly with anti-tumor necrosis factor agents, has resulted in improved symptoms and functions for many patients, and clinical research increasingly suggests that effective therapy can also prevent destruction in the spine and other structures. Recent f ...[more]

PMID: 25343035

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Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

Dataset Information

Advances in managing ankylosing spondylitis.

Publications

Advances in managing ankylosing spondylitis.

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