Pathogenesis and Biomarkers in Spondyloarthritis: Clues from Microarray Analyses
David T. Y. Yu.
Two areas of spondyloarthritis (SpA) are subjects of intense research: pathogenesis and identification of biomarkers of disease activity. Concerning pathogenesis, it is commonly accepted that HLA-B27 is an essential gene for a prototype of SpA called ankylosing spondylitis (AS). Although a MHC class I molecule, studies of HLA-B27 have revealed biology unusual for other HLA class I alleles. The latest surprise is that this protein has a slow rate of biogenesis inside the endoplasmic reticulum (ER), and hence might in certain circumstances potentially lead to generation of the ER unfolded protein response. First demonstrated with cultured cell lines, this hypothesis has found fortuitous support during microarray screening of synovial fluid cells derived from SpA patients. Preliminary experiments based on microarray analyses suggest that the targets of the ER responses are cells of the macrophage lineage. Previous research on AS has been focused almost exclusively on T lymphocytes. These microarray results provide investigators with new target cells for future studies. Concerning biomarkers of disease activity, microarray analyses have also provided support for a previously suspected candidate: metalloproteinase-3 (MMP-3). The potential usefulness of serum levels of this biomarker has now been demonstrated in cohorts of patients derived from three different countries. If reproducible in additional cohort studies, it might become a tool in clinical practice.
Keywords: MMP, Ankylosing Spondylitis Disease, TNF blockers, HLA class I alleles, microarray chips
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