Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of multiple autoantibodies (AAb), especially anti-dsDNA Ab. It is not known whether an aberrant V(D)J recombination process itself predisposes to the generation of autoreactive Ab, or whether abnormalities in selection influences can lead to the generation of AAb. Immunoglobulin (Ig) heavy (H) and Ig light chains of an antibody are generated from variable (V), diversity (D) and joining (J) gene segments through V(D)J rearrangements. Diversification mechanisms inherent to the rearrangement reaction ensure that D elements can potentially be used in all reading frames (RF). In addition, D and J elements of the IgH chains encode the complementarity determining region (CDR) 3 that constitutes a significant part of the Ig antigen binding site. Since it has been suggested that the CDR3 of Ab in SLE is different from that found in normals, we compared the CDR3 obtained from Ab of an untreated SLE patient with that from normal individuals. D segments of Ab from normal donors are preferentially used in RF II (26/48, p* 0.001) that most often encodes hydrophilic antibodies. Comparison of productive and nonproductive rearrangements suggests, that this is the result of the recombinational process rather than selection. In contrast, RF II was significantly less often used in SLE Ab (4/17, p* 0.03). In both, normal and SLE Ab, D segments were significantly less often found utilizing RF that encode stop codons. Similar to the usage of RF II, in normals this seems to be the result of the recombination process rather than selection. Because of the low number of nonproductive rearrangements in the SLE analysis it is not possible to estimate whether this results from selection or the recombination process. In contrast to the analysis of the RF, no significant difference between the length or composition of the CDR3 from SLE and normal Ab was found.
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
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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