Abstract
CD40 is a surface protein originally identified on B cells. Its interaction with CD40L on T cells plays an important role in the activation, proliferation and differentiation of B cells. During the recent years, CD40 has been identified in an expanding list of hemopoietic and nonhemopoietic cells and has received an increased interest based on its role in a variety of cell-mediated responses and its potential to participate in the pathogenesis of chronic inflammatory disorders. Sjogren's Syndrome (SS) is an autoimmune exocrinopathy, which is characterized by chronic lymphocytic infiltration of exocrine glands and aberrant activation of epithelial tissues. To investigate the participation of CD40 in the pathogenesis of SS, the expression of this protein was studied in cultured non-neoplastic salivary gland (SG) epithelial cell (SGEC) lines as well as in minor SG biopsies obtained from 17 SS patients and 12 controls. Immunocytochemical and flow cytometric analysis has revealed the occurrence of constitutively expressed CD40 molecules on the surface of our long-term cultured SGEC lines, which could be further induced by IFNγ and IL-1β, but not TNFα, IL-4, IL-6, GM-CSF and IFNγ. In SGEC lines derived from SS patients, the spontaneous expression of membranous CD40 was significantly higher compared to controls (P < 0,001), which is likely suggestive of their activated status. In SG biopsies, CD40 was constitutively expressed by B cells, ductal epithelial cells and endothelial cells but not by other glandular cell types, such as acinar cells, myoepithelial cells and fibroblasts. In addition, CD40L staining was also detected in 30-50% of the infiltrating T cells in the biopsies of SS patients. Our results possibly reveal the immunoregulatory potential of SGEC and lend further support to a model of intrinsic activation in salivary epithelia in SS, whereby these cells actively participate in the induction and maintenance of lymphocytic infiltrates of patients.
Highlights
The presence of autoantibodies directed to citrullinated antigens in serum is highly specific for rheumatoid arthritis (RA)
We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA)
Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, this did not reach statistical significance (P = 0,18)
Summary
The presence of autoantibodies directed to citrullinated antigens in serum is highly specific for RA. Anti-CCP concentrations (expressed in Units per mg total IgG) were on average 1.34 times higher in SF compared to serum (n = 20, P < 0.05) or 1.37 when only positive samples were included (n = 11, P < 0.05) Conclusion: Citrullinated antigens are present in the synovia of both RA and control patients with similar prevalence. At higher concentrations (>1ng/μl) of RNA-oligonucleotides unspecific hybridization-signals prevailed in tissues of all diseases (even in normal controls) The combination of both methods (in situ-hybridization and immunohistochemistry) identifies the single cells inside the synovial lining layer which contains the highly expressed RAB3 “Kreisler” (maf B) gene. Conclusions: These data demonstrates for the first time that statins (and fluvastatin) are able to inhibit an endothelial proadhesive and pro-inflammatory phenotype induced by different stimuli including anti-β2GPI antibodies or pro-inflammatory cytokines These findings suggest a potential usefulness for statins in the prevention of the APS pro-atherothrombotic state
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