Lupus autoantibodies to native DNA preferentially bind DNA presented on PolIV

Abstract

Summary While immunoglobulin G (IgG) antibodies to double‐stranded (ds)DNA are serological markers of systemic lupus erythematosus (SLE), not all antibodies to DNA (anti‐DNA) are able to cause tissue damage to a similar extent. It has been proposed that anti‐DNA‐induced renal damage could be linked to differences in the fine specificity of the antibodies. In an attempt to gain insight into their fine binding properties, we investigated the cross‐reactivity of two human lupus monoclonal IgG anti‐dsDNA (B3 and RH14) to a recently described Escherichia coli PolIV (a DNA polymerase). These autoantibodies possess distinct pathogenic properties in severe combined immunodeficient (SCID) mice. Although both antibodies cause proteinuria, only RH14 induces early histological features of lupus nephritis. Both RH14 and B3 bound PolIV; however, they exhibited a marked difference in their reactivity to the PolIV–dsDNA complex. Alhough RH14 exhibited significant activity to the complex, the binding of B3 to PolIV complexed with dsDNA was almost abolished. Furthermore, there was a significant difference in the way the lupus sera recognized naked dsDNA and that presented on PolIV. Although 67% of lupus sera bound naked dsDNA, ≈ 90% of these sera (93% calf thymus DNA; 90% synthetic oligonucleotide) reacted to the complex when dsDNA was presented on PolIV. Thus, the IgG anti‐dsDNA likely to exist in lupus patients may be distinguished into those that recognize dsDNA in the context of PolIV and those which do not. This difference in binding ability may help to distinguish those dsDNA antibodies that are more pathogenic.

Inhibition mechanisms of hemoglobin, immunoglobulin G, and whole blood in digital and real-time PCR

“…In 1979, the nature of anti-DNA activity of IgG from human serum of healthy people was studied, and it was found that a small portion of IgG binds to ssDNA [ 33 ]. In a study that focused on lupus monoclonal antibodies it was found that there are different binding mechanisms, where some antibodies bind to dsDNA alone and some preferably bind to dsDNA in a complex with a DNA polymerase [ 34 ]. The thermodynamics of antibody binding to DNA has been investigated with 20mer duplex DNA molecules.…”

Understanding the Neurotrophic Virus Mechanisms and Their Potential Effect on Systemic Lupus Erythematosus Development

“…This phenomenon triggers the production of autoantibodies and pro-inflammatory cytokines, including IFN-γ, IL-6, IL-23, and IL-17, among other molecules [255][256][257][258]. This results in tissue damage, compromising the integrity of the different tissues of individuals affected by this pathology [259,260]. This condition possesses the capability to impact all the organs that are encompassed by the other autoimmune disorders previously mentioned.…”

PCR inhibition in qPCR, dPCR and MPS—mechanisms and solutions

“…The interactions between antibodies and DNA have also been studied in other fields, and it has been shown that a small portion of IgG in serum of healthy people binds to ssDNA [87]. Further, researchers studying lupus monoclonal antibodies showed that there are different binding mechanisms of antibodies to DNA, where some preferentially bind to dsDNA in complex with a DNA polymerase [88]. Another molecule that has been identified as a nucleic acid inhibitor is collagen in bone, causing inhibition by interaction with template DNA which affects the DNA polymerase processivity [67,89].…”