Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity

Abstract

Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials.

Differential Immuno-Reactivity to Genomic DNA, RNA and Mitochondrial DNA is Associated with Auto-Immunity

“…Persistent circulation of anti-dsDNA antibodies suggests that autoimmunity to nucleic acid containing molecules is essential for SLE pathogenesis. In addition to dsDNA, histones, ribonucleo-proteins and dsRNA have been shown to be targets for immune response in SLE [6,7,8]. Recently, potential immunogenicity of peroxy-nitrite modified mitochondrial DNA (mtDNA) has been shown in SLE [9].…”

Utility of Autoantibodies as Biomarkers for Diagnosis and Staging of Neurodegenerative Diseases

“…Although the pathogenesis of SLE is not completely understood, genetic, environmental, and autoimmune factors have been implicated. Both humoral and innate immunity are thought to play a key role in the disease as numerous studies have identified dysfunction of the immune system and loss of tolerance during the pathogenesis of SLE (Ippolito et al, 2011). Several autoantibodies associated with SLE have been identified that target nuclear, cytoplasmic, surface membrane, and extracellular antigens present in various cell types and tissues (Ippolito et al, 2011;Sherer, Gorstein, Fritzler, & Shoenfeld, 2004;Yaniv et al, 2015).…”

“…Both humoral and innate immunity are thought to play a key role in the disease as numerous studies have identified dysfunction of the immune system and loss of tolerance during the pathogenesis of SLE (Ippolito et al, 2011). Several autoantibodies associated with SLE have been identified that target nuclear, cytoplasmic, surface membrane, and extracellular antigens present in various cell types and tissues (Ippolito et al, 2011;Sherer, Gorstein, Fritzler, & Shoenfeld, 2004;Yaniv et al, 2015). One specific type of autoantibody broadly implicated in SLE, antinuclear autoantibody (ANA), is comprised of several subtypes that are primarily directed against nucleic acids and their bound proteins, as well as small nuclear Figure 1 In chronic diseases, such as rheumatoid arthritis (RA) and Alzheimer's disease (AD), many cells in regions of evolving pathology express PADs.…”

Modulating the survival and maturation system of B lymphocytes: Current and future new therapeutic strategies in systemic lupus erythematosus

“…[3][4][5] In general, these AA are able to induce an inflammatory process and tissue damage by the formation and deposition of immune complexes or their formation in situ. It has been shown that immune complexes containing RNA or DNA may induce production of type I interferon (IFN), which promotes the inflammatory response.…”