Abstract
The production of rheumatoid factor (RF) and antinuclear antibody by B-cells could depend on different cytokines action. We evaluated IL-13 serum levels in 230 patients with autoimmune rheumatic diseases including rheumatoid arthritis (RA) [M/F=22/62; mean age=55.2 (25-76) yrs; mean disease duration = 116 (5-605) months], SLE [M/F=17/97; mean age=38.3 (15-70) yrs; mean disease duration = 77 (1-456) months], Sjogren's syndrome (SS) [M/F=2/50; mean age = 55.2 (26-81) yrs; mean disease duration = 82 (3-540) months], and systemic sclerosis (ScS) [M/F = 1/31; mean age=50.6 (20-73) yrs; mean disease duration = 113 (12-276) months], in order to investigate the relationship of this cytokine with the autoantibody profile. Serum levels of IL-13 (pg/ml) were significantly increased in patients with RA (P < 0.00003), with SLE (P < 0.03), with SS (P < 0.0007), with ScS (P < 0.025) as compared to controls. IL-13 serum levels correlated with those of RF in RA (P < 0.00001), SLE (P < 0.003) and ScS (P < 0.03). IL-13 levels were higher in RA (P < 0.0002), SLE (P < 0.004) and ScS (P < 0.05) patients with RF than patients without RF. SS patients with anti-SSA/Ro antibodies had significantly higher IL-13 levels than SS patients without this autoantibody (P < 0.036). No statistically significative correlation was found between IL-13 levels and any other antinuclear autoantibody or total immunoglobulin levels or main clinical features of each disease. This study suggests that IL-13 may be involved in the pathogenesis of autoimmune rheumatic diseases, with a relevant role on RF production. In SS, the lack of correlation between IL-13 and RF is probably due to the peculiar characteristics of this antibody in the disease. We can conclude that the mechanisms involved in RF synthesis recognise different pathways depending on the underlying autoimmune disease.
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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