Anti-nuscleosome antibody, a reliable indicator for lupus nephritis

Abstract

Systemic lupus erythematosus (SLE) is characterized by the presence of antinuclear antibodies (ANA). ANAs are aimed against native DNA, as well as histone proteins and small nuclear ribonucleoproteins, also could be targeted against the entire chromatin, consisted of nucleosomes. Herein, we assessed the frequency and the concentration of anti-nucleosome antibodies (aNS) in a group of 107 Hungarian patients with SLE. Moreover, correlations between these autoantibody concentrations and disease activity, as well as organ manifestations, mainly renal symptoms were evaluated. The occurrence of positive aNS, anti-dsDNA and anti-histone (aH) antibodies were 39.2, 28.0 and 47.6%, respectively. All the three autoantibodies were represented with significantly higher titers in patients with lupus nephritis. A positive correlation was found between the concentration of these autoantibodies and disease activity. The long disease duration (mean 8.5 years) and consequent low disease activity (mean disease activity index: 3.28) could be the reason for the relatively low occurrence of ANAs amongst patients. Besides anti-dsDNA, the assessment of aNS and aH antibodies could be useful in the diagnosis and follow-up of SLE. The authors discuss the possible role of aNS autoantibodies in the pathogenesis of lupus nephritis.

Anti-ribosomal P protein IgG autoantibodies in patients with systemic lupus erythematosus: diagnostic performance and clinical profile

“…Our observations regarding anti-dsDNA are in line with other classic findings depicting an association with renal involvement, as well as in relation to lower disease duration and higher disease activity [35]. …”

Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE

“…The presence of anti-dsDNA Ab is used as a clinical biomarker associated with a poor prognosis of lupus and is strongly associated with the development of nephritis [35,36]. Hence, serum samples of treated MRL/lpr mice were analyzed for the presence of circulating pathogenic antinuclear antibodies (ANA).…”

“…The presence of serum anti-dsDNA Ab along with the presence of autoantibody secreting cell types are both correlated with an increased likelihood of developing lupus nephritis [12,35]. Lupus nephritis consists of several overlapping renal pathologies that most commonly include glomerulonephritis, necrosis and sclerosis associated with chronic renal inflammation.…”

The constant region affects antigen binding of antibodies to DNA by altering secondary structure

“…Abs both to DNA and histone are believed to be important in the pathogenesis of SLE (Muller et al, 2008; Kiss et al, 2009; Cohen-Solal and Diamond, 2011; Pavlovic et al, 2011), and at least for pathogenic anti-DNA Abs there is a bias towards Abs of the IgG2a and IgG3 isotypes (Sugiyama et al, 2004; Baudino et al, 2006; Mannoor et al 2012; Moser et al, 2012). It is important to note that variations in binding between PL9-11 switch variants were not only related to C region differences, but also to the properties of the Ag studied.…”