Comprehensive Longitudinal Surveillance of the IgG Autoantibody Repertoire in Established Systemic Lupus Erythematosus

Abstract

Objective. To investigate the role of epitope spreading in established systemic lupus erythematosus (SLE). Methods. IgG autoantibody reactivity with 398 distinct recombinant proteins was measured over a period of 6 years in 69 SLE patients and compared to that in 45 controls. Changes in mean fluorescence intensity (MFI), number of autoantibodies to distinct antigens, and reactivity with distinct clones of established antigenic targets (e.g., U1 RNP, Sm, and ribosomal P) representing epitope fine mapping were assessed. Linear mixed modeling, adjusted with Bonferroni correction for age and sex, was applied.Results. The total number of autoantibodies, mean MFI, and number of autoantibodies in epitope fine mapping were higher in SLE patients compared to controls (P < 0.0001). The total number of antibodies to distinct autoantigens remained stable over time, while the mean MFI decreased over time in SLE (P < 0.021). SLE patients showed variable recognition of epitopes in fine mapping over time. In particular, in SLE patients, more clones of the U1 RNP complex were recognized at the time of new organ involvement (+0.65) (P = 0.007). Mean MFI was higher in patients with lupus nephritis (P = 0.047). The time-averaged MFIs of 22 individual autoantibodies (including double-stranded DNA [dsDNA]) were higher, after Bonferroni correction, in SLE (P < 0.0001). The MFIs of dsDNA and histone cluster 2 H3c were associated with scores on the Systemic Lupus Activity Measure (P < 0.0001).Conclusion. Longitudinal surveillance of the IgG autoantibody repertoire in established SLE reveals evidence of sustained breadth of autoantibody repertoire without significant expansion. Associations of disease activity with dsDNA and with histone H3 autoantibodies were confirmed.

Applications of Protein Microarrays in Biomarker Discovery for Autoimmune Diseases

“…Another consideration is the sampling time. Longitudinal prospective studies using certain biomarker panels could be applied in disease prevention, activity monitoring, as well as prognosis following treatments (105)(106)(107). Furthermore, additional large cohorts of samples should be collected to prove any novel discoveries.…”

Profiling of IgG antibodies targeting unmodified and corresponding citrullinated autoantigens in a multicenter national cohort of early arthritis in Germany

“…Baseline serum blood samples of 411 patients from a multicenter national cohort of early arthritis (Course And Prognosis of Early Arthritis, CAPEA) [16] were obtained for a multiplex analysis of 390 autoantibodies to distinct proteins (supplementary table 1) by Luminex technology as described previously [17]. Inclusion criteria for the CAPEA study were age above 18 years with clinical arthritis for ≤ 26 weeks in 2 joints or ≥ 1 joint with morning stiffness ≥ 30 min.…”

“…IgG reactivities against 390 unmodified recombinant proteins and 390 corresponding in vitro citrullinated recombinant proteins were assessed: Luminex bead-based antigen arrays were used for the multiplex analysis of IgG autoantibody reactivity as previously described [17,18]. In total, 390 antigens were selected based on literature data, and autoantibody reactivity data identified in previous high-content profiling studies in rheumatoid arthritis and SLE [18,19].…”

Immune Profiling and Precision Medicine in Systemic Lupus Erythematosus

“…Autoantibodies, such as anti-dsDNA antibodies and anti-Ro antibodies, are present many years before the diagnosis of SLE and progressively accumulate until clinical onset [108]. Recent analysis with multiplex bead-based antigen detection for 398 antigens, showed that the number of epitopes recognized by autoantibodies generally do not change over six years in established SLE patients [109]. dsDNA and histone H3 autoantibodies were notable exceptions and constituted disease activity markers.…”