Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes

Abstract

SummaryThe objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.

DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs

“…Despite the decreased percentages and impaired in vitro-suppressive activity of their Tregs, Dock8 -/-mice aged for 12 months had normal weight gain and did not develop lymphadenopathy, splenomegaly, anemia, thrombocytopenia, or gastrointestinal inflammation. In addition, their sera did not exhibit increased reactivity to HEp-2 cell antigens or to the 128 autoantigens included in the University of Texas Southwestern panel (37) compared with WT controls (data not shown). Intraperitoneal administration of the TLR3 agonist poly(I:C) for 3 months to mimic microbial stimulation did not elicit autoantibody formation against HEp-2 cells and did not provoke autoimmune disease in Dock8 -/-mice (data not shown).…”

B cell–intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice

“…10 Screening for a broad panel of IgM and IgG autoantibodies was performed with autoantibody arrays (University of Texas Southwestern Medical Center, Genomic and Microarray Core Facility) as described. 14 …”

Screening Autoantibody Profiles in Systemic Rheumatic Disease with a Diagnostic Protein Microarray That Uses a Filtration-Assisted Nanodot Array Luminometric Immunoassay (NALIA)

“…In studies with a limited number of samples, investigators demonstrated that IgM autoantibodies predominated over IgG in patients with incomplete lupus erythematosus (at least 1 but less than 4 of the criteria for SLE (12 )). IgG usually predominates in SLE, however (13 ). It will be of interest to use NALIA arrays to evaluate this observation by detecting IgM and IgG autoantibodies separately rather than simultaneously, which was the approach we used.…”