Anticorpos anti-nucleossoma em portadores de lúpus eritematoso sistêmico

Abstract

More recent studies on the pathogenesis of SLE suggest that the nucleossome, chromatin’s main structure, might be the antigen playing a leading role in the development of the immune response in lupus. For several years this place had been assigned to DNA, mainly due to the fact that anti-dsDNA antibodies were found to be associated with lupus activity, specially in relapsing nephritis. Observations driven from experimental animal studies and clinicai investigations as well, further indicated that the hypothesis of being DNA the main immunogen in SLE could no longer be maintained. Attempts to immunize animais with isolated DNA did not succeed, and infusion of artificially built DNA-anti- dsDNA immune complexes failed to mimick disease. In addition, in several models, including mice strains bearing spontaneous LES, and in humans, severe forms of lupus have been observed without the detection of anti-dsDNA antibodies. In the studies where other components of chromatin, specially histones-bound DNA, the nucleossome, were injected in pre-immune animais, this led to an exacerbation of the auto-immune response and to nephritis development. It becomes thus evident that nucleossomes play a key role in the stimulation of the pathogenic T-cell and in the development of immune disregulation observed in LES.An additional argument favouring this hypothesis is the observation that DNA circulates in the blood of these individuais under the form of nucleossomes derived from a disturbed apoptosis process, as suggested by some studies. The Identification of nuclear material in human renal tissue and the fínding of anti-nucleossome antibodies in kidney eluates additionally suggest that a nephritogenic role may be exerted by the nucleossome. In face of this evidence suggesting a primordial role for the nucleossome in the pathogeny of lupus, a clinicai study was undertaken in order to evaluate the value of anti-nucleossome antibodies in LES diagnosis, its correlation with disease activity indexes, association with clinicai and laboratory parameters, specially nephritis, lenghth time of disease, type and length of treatment. We performed a cohort sudy including 71 patients with LES, 64 women and 7 men, mean age=30,01±ll,48, mean time of disease=37,7±47,87 months, treated at Hospital Universitário Walter Cantídio and Hospital Geral Dr. César Cais,from March 1995 to November 1997. All the patients fullfílled at least four criteria of the American College of Rhumatology for the diagnosis of lupus and disease was classified according to two activity indexes, SLEDAI and LACC. 63.4% of the patients showed active lupus and 77.4% of them had renal involvement. Blood samples were drawn in order to determine anti-nucleossome, anti-dsDNA and anti-histones antibodies titers, through ELISA. Normal values for these tests were established from a group of volunteer blood donors (mean value + 3 x standard deviations) and the tests were also performed in rhumatoid arthritis patients and in patients with primary glomerular disease in order to cálculate its sensitivity and specificity. Comparison between groups showed that anti-nucleossome and anti-dsDNA antibodies titers were significantly higher in lupus patients than in the other groups (p<0.0001). Sensitivity of the antinucleossome antibody was 71.8%, greater than the 43.6% value found for the anti-dsDNA antibody (p<0.0001). On the other hand, its specificity, 84.2%, was lower than the one observed for the anti-dsDNA antibody (p<0.009). Serum leveis of both antibodies correlated to disease activity indexes (anti-nucleosome and SLEDAI: r=0,486,p<0,001 ; anti-nucleosome and LACC: r=0,536,p<0,001 ; anti-dsDNA and SLEDAI: r=0,449,p<0,0001 ; anti-dsDNA