Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis.

Metabolic and Renal Function Testing, University Teaching Hospital, Besançon, France
Joint, bone, spine: revue du rhumatisme (Impact Factor: 2.25). 06/2007; 74(3):304-5. DOI: 10.1016/j.jbspin.2006.11.005
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    ABSTRACT: New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis.
    Clinics (São Paulo, Brazil) 12/2014; 69(10):688-93. DOI:10.6061/clinics/2014(10)07 · 1.59 Impact Factor
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    ABSTRACT: The group of diseases classified as seronegative spondyloarthritis or enthesoarthritis is characterized by typical osteoarticular and extra-articular manifestations. Diverse patterns of disease can affect different members of the same family and may show different features in the same patient, with clinical overlaps thwarting the differential diagnosis. An anatomo-pathological hallmark in enthesoarthritis is the inflammatory process in the synovio-entheseal sites. The inflammatory microenvironment of synovio-entheseal complex, named enthesitis, is characterized, after an initial inflammatory/erosive phase, by a subsequent phase of neobone apposition, which seems to progress independently from the previous erosive phase, suggesting that the physiopathogenetic mechanisms that underlay the two phases are driven by different pivots. The structural damage is characterized by excessive neobone formation, with the syndesmophyte as a typical lesion. The process underlying their formation is not fully understood, although there are many useful information to clarify the physiopathogenetic puzzle. The primum movens of the enthesitic process is the micro-trauma to which entheses are subject, especially in the lower limbs, for biomechanical reasons. The inflammatory process is facilitated by the sequential structure of the organ enthesis, constitutionally devoid of sub-enthesitic cortical bone and closely related to the underlying trabecular bone and the medullary vascular system. The reparative attempt from the vascular system, thanks to the activating action of certain loco-regional cytokines, such as TNF α, conditions the possible deposit in the enthesis of molecules derived from other organic sites and able, especially in HLA-B27+ subjects, to activate and self-renew an immune-mediated inflammatory process following the initial mechanical process.
    Clinical and Experimental Medicine 02/2015; DOI:10.1007/s10238-015-0341-x · 2.82 Impact Factor
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    ABSTRACT: Background Interleukin-37 (IL-37) has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of ankylosing spondylitis (AS) has not been investigated. Here, we examined the serum levels of IL-37 and its clinical association in AS, and explored the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) from AS patients.Methods The mRNA levels of IL-37, TNF-¿, IL-6, IL-17, and IL-23 in PBMCs and their serum concentrations from 46 AS patients were examined by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunoassay (ELISA), respectively. The correlations between serum IL-37 levels with disease activity, laboratory values and pro-inflammatory cytokines in AS were analyzed by Spearman correlation test. PBMCs from 46 AS patients were stimulated with recombinant IL-37 protein, expressions of TNF-a, IL-6, IL-17 and IL-23 were determined by RT-PCR and ELISA.ResultsCompared to healthy controls (HC), AS patients and active AS patients showed higher levels of IL-37 in PBMCs and serum respectively. Strikingly, serum IL-37 levels were higher in AS patients with osteoporosis than those without. Serum levels of IL-37 were correlated with laboratory values as well as TNF-¿, IL-6 and IL-17, but not IL-23 in patients with AS. The productions of pro-inflammatory cytokines such as TNF-a, IL-6, IL-17, IL-23 in PBMCs from AS patients were obviously attenuated after recombinant IL-37 stimulation, but not in the HC.Conclusion The higher levels of IL-37 were found in AS patients, which were correlated with disease activity and AS related pro-inflammatory cytokines. More importantly, IL-37 inhibits the expressions of the pro-inflammatory cytokines from PBMCs in AS patients, indicating the potential anti-inflammatory role of IL-37 in AS.


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