The Spectrum of Anti-Chromatin/Nucleosome Autoantibodies: Independent and Interdependent Biomarkers of Disease

Abstract

Autoantibodies directed to chromatin components date back to the discovery of the LE cell and the LE cell phenomenon circa 1950, and subsequent evidence that major components of that reaction were chromatin components and histones in particular. Over time, immunoassays ranging from ELISA and line immunoassays to more modern bead-based assays incorporated histone and DNA mixtures, purified histones, and purified nucleosomes leading to a more thorough understanding of the genesis and pathogenetic relationships of antibodies to chromatin components in systemic lupus erythematosus and other autoimmune conditions. More recently, interest has focussed on other components of chromatin such as high mobility group (HMG) proteins both as targets of B cell responses and pro-inflammatory mediators. This review will focus on immunoassays that utilize chromatin components, their clinical relationships, and newer evidence implicating HMG proteins and DNA neutrophil extracellular traps (NETs) as important players in systemic autoimmune rheumatic diseases.

Flares in systemic lupus erythematosus: diagnosis, risk factors and preventive strategies

“…Serum autoantibodies and complement factors are widely used for measuring activity and diagnosing flares in SLE. 22 Antibodies to double-stranded DNA (anti-dsDNA) are found in approximately 50% of SLE patients, 23 and their serum levels correlate with lupus activity, especially nephritis. [24][25][26][27] However, the magnitude of this association varies significantly across different studies with positive likelihood ratios ranging from 0.88 to >10.…”

Anti-dsDNA Antibodies are one of the many autoantibodies in systemic lupus erythematosus

“…Since these early publications, there have been many published papers to support the importance of anti-dsDNA antibodies as a biomarker in the diagnosis, pathogenesis, and prognosis of SLE (reviewed in 2 , 13 , and 14 ).…”

“…In the review by Mehra and Fritzler 14 , it was concluded that the anti-chromatin/nucleosome antibodies may be superior to anti-dsDNA antibodies as a biomarker for SLE. In summary, this brief analysis of the literature supports the conclusion that anti-dsDNA antibodies are not specific or the best biomarker for SLE.…”

A novel DNA/histone H4 peptide complex detects autoantibodies in systemic lupus erythematosus sera

“…Similar observations are applicable to anti-nucleosome antibodies, a family of anti-chromatin antibodies, measured by solid phase assays using intact or H1-stripped nucleosomes that detect antibodies reactive with DNA, histones, or determinants formed by the association of DNA with histones [ 15 , 16 ]. Anti-nucleosome antibodies display a sensitivity and specificity similar to solid phase assays for anti-dsDNA antibodies, and similar correlations with disease activity and organ involvement in SLE.…”