An Update on Antibodies to Necleosome Components as Biomarkers of Sistemic Lupus Erythematosus and of Lupus Flares

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with variable clinical expression. It is a potentially devastating condition affecting mostly women and leading to clinically unpredictable outcomes. Remission and flares may, in fact, alternate over time and a mild involvement limited to few articular sites may be followed by severe and widespread organ damage. SLE is the prototype of any autoimmune condition and has, for this reason, attracted the interest of basic immunologists. Therapies have evolved over time and clinical prognosis has, in parallel, been improved. What clinicians still lack is the possibility to use biomarkers of the disease as predictors of outcome and, in this area, several studies are trying to find solutions. Circulating autoantibodies are clearly a milestone of clinical research and the concrete possibility is to integrate, in the future, classical markers of activation (like C3) with target organ autoantibodies. Anti-dsDNA antibodies represent a basic point in any predictive attempt in SLE and should be considered the benchmark for any innovative proposal in the wide field of target organ pathologies related to SLE. DNA is part of the nucleosome that is the basic unit of chromatin. It consists of DNA wrapped around a histone octamer made of 2 copies each of Histone 2A, 2B, 3, and 4. The nucleosome has a plastic organization that varies over time and has the potential to stimulate the formation of antibodies directed to the whole structure (anti-nucleosome) or its parts (anti-dsDNA and anti-Histones). Here, we present an updated review of the literature on antibodies directed to the nucleosome and the nucleosome constituents, i.e., DNA and Histones. Wetriedto merge the data first published more than twenty years ago with more recent results to create a balanced bridge between old dogma and more recent research that could serve as a stimulus to reconsider mechanisms for SLE. The formation of large networks would provide the chance of studying large cohorts of patients and confirm what already presented in small sample size during the last years.

Clinical characteristics of oral mucosal lesions in patients with systemic lupus erythematosus and their association with clinical and laboratory parameters

“…Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of various autoantibodies such as antinuclear and anti-ds DNA (anti-dsDNA) [1,2]. Lupus erythematosus (LE) includes a broad spectrum of manifestations, from a cutaneous-limited type (CLE) to a systemic type.…”

Harnessing Tolerogenic Histone Peptide Epitopes From Nucleosomes for Selective Down-Regulation of Pathogenic Autoimmune Response in Lupus (Past, Present, and Future)

“…First of all as mentioned above, only particular subclasses of IgG anti-DNA antibodies are more closely associated with a pathogenic potential in lupus patients and mice, and these pathogenic IgG antibodies belong to Th1-induced isotype classes. In lupus patients, Th1induced anti-DNA IgG1antibodies are always elevated before the occurrence of renal relapse, and IgG1 plus IgG2 anti-DNA antibodies are found in patient's renal eluates, whereas in lupus prone mice, murine Th1-induced IgG2a, IgG2b, and IgG3 anti-DNA are more frequently eluted from kidneys with active nephritis (39,42,(86)(87)(88). In contrast to T FH cells which conventionally produce IL-21; Th1 cytokine IFNg not only mediates class switch for the nephritogenic isotypes, but Th1 derived IFNg signal is also critical for autoantibody production by germinal center B cells (89,90).…”

Chicken-or-egg question: Which came first, extracellular vesicles or autoimmune diseases?

“…anti-inflammatory drugs, immunosuppressive agents, and biologic agents. 129 However, clinicians still lack biomarkers for prediction of disease outcome, and several studies are aimed at addressing this issue.…”

“…SLE diagnosis is achieved through clinical observations and laboratory examinations, and therapy is determined depending on disease manifestations and severity. Clinical prognosis and treatments have improved over time, and treatment chiefly comprises the use of steroidal and nonsteroidal anti‐inflammatory drugs, immunosuppressive agents, and biologic agents 129 . However, clinicians still lack biomarkers for prediction of disease outcome, and several studies are aimed at addressing this issue.…”