Antinucleosome antibodies – a new marker of lupus nephropathy

Introduction. In recent years some reports on the diagnostic and prognostic value of antinucleosome antibodies in patients with systemic lupus erythematosus (SLE) have been published. Nucleosome is a component of chromatin consisting of histones H1, H2A, H2B, H3 and H4 with a stretch of DNA wrapped around. Nucleosomes are released in the process of cell apoptosis.

Objective. To evaluate the frequency of antinucleosome antibodies in SLE patients and its correlation with renal involvement and disease activity assessed by SLAM score.

Material and methods. The material comprised 52 patients with SLE positive for antinuclear antibodies in indirect immunofluorescence (IIF) test on Hep2 cells. Anti-dsDNA antibodies were detected by IIF test using Crithidia luciliae as an antigen substrate. Detection of antinucleosome antibodies and identification of specificity of ANAs were performed using the EUROLINE test (Euroimmun Medizinische Labordiagnostika Lubeck, Germany). Sera from 50 patients with systemic scleroderma were also tested as a control group.

Results. Antinucleosome antibodies were found in 20 out of 52 (38%) sera of patients with SLE and in 1 out of 50 (2%) sera of patients with systemic scleroderma. Statistical analysis showed no significant difference between patients with or without antinucleosome antibodies regardless of sex, age, age in the initial phase of the disease and its duration. Antinucleosome antibodies were detected in sera with high titers (320-5120) of antinuclear antibodies. ANA titers in patients without antinucleosome antibodies were significantly lower (p = 0.0119). Anti-dsDNA antibodies coexisted, statistically, more frequently with antinucleosome antibodies in comparison with the group without antinucleosome antibodies (p < 0.001). In 55% of patients with antinucleosome antibodies pathological changes within the kidneys were observed with a typical proteinuria > 0.5 g/day and/or nephropathy confirmed by renal biopsy. In 30% of patients with antinucleosome antibodies proteinuria below 0.5 g/day was found while 15% of patients had no renal changes. A statistical analysis showed that the renal pathology was more often found in cases positive for antinucleosome antibodies (p = 0.0025 and p = 0.0024 respectively) and also in patients with anti-dsDNA antibodies (p = 0.0065). The activity of SLE according to the SLAM scale was higher in patients with antinucleosome antibodies (median 11) than in those without the antibodies (median 7.5). Wilcoxon’s test did not reveal statistical significance, but the result of p = 0.0648 implies a distinct tendency for higher values of the SLAM scale among patients with anti-nucleosome antibodies.

Conclusions. Our results suggest that anti-nucleosome antibodies might be a valuable immunological diagnostic marker in SLE, especially of lupus nephropathy.