Background Systemic lupus erythematosus (SLE) is considered driven by immune complexes (IC), and autoantibodies are supposed to participate in IC formation. Thus, the fraction of autoantibodies participating in IC formation merits interest as a diagnostic and/or prognostic marker. We have developed a technique to quantify autoantibody content in IC (Sohrabian et al. Ann Rheum Dis 2015;74(Suppl 1):A74).
Objectives To evaluate quantification of autoantibodies in IC as a measure of disease activity and prognosis for response in belimumab-treated SLE patients.
Methods Fifty-five SLE cases classified according to the ACR criteria were treated with belimumab and followed for one year. High disease activity was defined as SLE Disease Activity Index 2000 (SLEDAI-2K) ≥10, or as low levels of complement factors C3 and/or C4. Treatment responses were recorded using the SLE Responder Index (SRI), or as a value 0 for modified SLEDAI-2K with suppression of autoantibody and complement data (clinical remission). Low disease activity was also recorded as Lupus Low Disease Activity State (LLDAS). Response data were recorded at 3, 6 and 12 months.
IC were purified from sera by binding to C1q-coated beads, and thereafter eluted. Autoantibody levels were determined in unmodified serum and in solubilised IC with addressable laser bead immunoassay (FIDIS Connective, Theradiag, Paris) for autoantibodies against dsDNA, histones, ribosomal P antigen, proliferating cell nuclear antigen (PCNA), SSA/Ro60, SSA/Ro52, SSB, Sm, U1RNP and the Sm/RNP complex. Autoantibody levels in serum and in IC were compared with Mann-Whitney's U test between patients with high and low disease activity at baseline and between patients with and without treatment response during the follow-up period.
Results Antibodies against dsDNA, SSA/Ro60 and Sm/RNP were found in 65%, 54% and 43%, other antibodies with lower percentages. Low complement levels were associated with high serum anti-dsDNA (p=0.003) and anti-ribosomal P antigen (p=0.008) levels, whereas high SLEDAI-2K associated with high anti-dsDNA (p=0.02) and anti-Sm/RNP (p=0.047) levels. Serum levels of antibodies against SSA/Ro60, SSB and SSA/Ro52 were lower in patients attaining LLDAS after 6 months (p=0.02, 0.051 [trend] and 0.04, respectively); these associations were stronger for corresponding IC fractions (p=0.01, 0.005, and 0.002, respectively).
Baseline levels of anti-dsDNA and anti-histones in IC associated with clinical remission ever during the follow-up period (p=0.003 and p=0.05). Low levels of anti-Sm and anti-Sm/RNP in serum but not in IC associated with clinical remission at month 6 (p=0.02 and 0.04 respectively), and for Sm/RNP also at month 3 (p=0.04).
Serum levels of all antibodies except SSA/Ro52 declined during the first 6 months, most prominently for dsDNA, histones ribosomal P, PCNA and Sm/RNP (p<0.0001 for all). Levels of antibodies in IC declined only for dsDNA (p=0.048).
Conclusions Autoantibody levels in serum and in IC show different associations to disease activity and to treatment response. High baseline anti-dsDNA levels in IC were most strongly associated with clinical remission, and decreased during belimumab treatment. Belimumab effect might primarily relate to autoantibodies in IC.
Disclosure of Interest None declared