Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by antibodies to DNA. These antibodies serve as markers of diagnosis and prognosis as well as serological markers of disease pathogenesis. While designated as autoantibodies, SLE anti-DNA target sites that are widely conserved among DNA of both self and foreign origin. This crossreactivity, a feature that appears common among SLE antinuclear antibodies, raises the possibility that immune responses to DNA may arise from stimulation by foreign DNA. This possibility has gained credence from observations that DNA from bacteria has potent immunological properties. These properties include polyclonal B cell activation and induction of cytokines such as IL-12. Furthermore, sera of normal human subjects contain anti-DNA antibodies which selectively bind to DNA from certain bacterial species. Immunization experiments in mice fully support the possibility that bacterial DNA can initiate or sustain SLE anti-DNA production. Recently, studies in mice have demonstrated that self DNA has immunological activity and is not inert as has been widely assumed. As shown in in vitro experiments, DNA from mammalian species including human and bovine, can inhibit cytokine production induced by bacterial DNA and, in certain, systems, the cytokine response to LPS. As such, self DNA may play a regulatory role in immunity, inhibiting response in settings of tissue inflammation or destruction where self antigens are released from cells. These considerations suggest that anti-DNA responses in SLE could result from a crossreactive response to foreign DNA or an aberrant response to self DNA in which the inhibitory signals of mammalian DNA are insufficient or overcome. In either instances, models of SLE must take into account that DNA plays an active role in immune responses and, depending upon species and base composition, may be stimulatory or inhibitory.

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)

Read more

Summary

Introduction

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

Objectives
Methods
Results
Discussion
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.