MP200
ANTIBODIES TO EARLY EBV ANTIGENS ASSOCIATE WITH THE GENERATION OF ANTI-DOUBLE-STRANDED DNA ANTIBODIES AND ACTIVITY OF LUPUS NEPHRITIS

INTRODUCTION AND AIMS: Epstein-Barr virus (EBV) has long been suggested to be one of the potential triggers of systemic lupus erythematosus (SLE). Recent results performed on cohorts of patients disclosing an intermediate disease activity point to an aberrant control of EBV reactivation in SLE. In this respect, of particular value seems to be the serological response to early EBV antigens. Our aim was to compare the antibody levels against early and late EBV antigens between healthy controls (C) and patients with lupus nephritis (LN) that is the condition having one of the worst prognoses among SLE manifestations.

METHODS: The study involved 51 C subjects and 39 patients with LN (mostly with class III and IV of LN). The median SLE disease activity index was 14 (range 0-38). It corresponded with the immunological activity reflected by a relatively high median level of anti-ds DNA antibodies 392.0 (range 16.8-1331 IU/ml) and low levels of C3 and C4 (medians 0.6 and 0.09; ranges: 0.29-1.45 and 0.04-0.34 g/l, respectively). The serum levels of EBV early antigen (EA), EBV viral capsid antigen (VCA) and EBV nuclear antigen-1 (EBNA-1) were determined in immunoglobulin (Ig) G, A and M classes using the specified enzyme-linked immunosorbent assays.

RESULTS: Ninety-five percent of LN patients and 80.4 % subjects from the C group were shown to be seropositive for EBNA-1 IgG, thus revealing previous EBV infection. This was confirmed by seropositivity for VCA IgG in 99.4 % of LN patients and 94% of C. The frequencies of EA antibody detection differed highly significantly between C and LN (21.6 v. 51.3% for EA-IgG, p=0.004; 5.9 v. 53.8% for EA-IgA, p<0.0001; 0 v. 35.9% for EA-IgM, p<0.0001, respectively). The serum levels of these antibodies followed the pattern observed for their frequency of detection. For EA-IgG the median values in C were 4.0 (range: 0.98-74.56 AU/ml) v. 8.1 in LN (range: 0.71-318.4 AU/ml) with p=0.0014. In case of EA-IgA, these values were 2.75 (range: 0.2-23.9 AU/ml) v. 8.6 (range: 0.37-304.9 AU/ml) with p<0.0001. For EA-IgM the corresponding levels were 2.7 (range: 0.8-6.2 AU/ml) v. 5.7 (range: 0.6-54.8 AU/ml) and p<0.0001. Furthermore, although it did not reach a statistical significance, anti-EBNA-1 IgG reactivity was lower in LN than in C. In addition, significant correlations between serum levels of EA-IgA and anti-ds DNA as well as EA-IgM and anti-ds DNA were observed (r=0.45, p=0.0041 and r=0.35, p=0.0387, respectively).

CONCLUSIONS: Our results confirm the previous suggestions that the control of EBV reactivation is lost in SLE. Moreover, responses to the lytic EBV antigens associate with the formation of anti-dsDNA antibodies and low complement activity, thus contributing to LN activity.