New insights into the role of antinuclear antibodies in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by antinuclear antibodies (ANAs) that form immune complexes that mediate pathogenesis by tissue deposition or cytokine induction. Some ANAs bind DNA or associated nucleosome proteins, whereas other ANAs bind protein components of complexes of RNA and RNA-binding proteins (RBPs). Levels of anti-DNA antibodies can fluctuate widely, unlike those of anti-RBP antibodies, which tend to be stable. Because anti-DNA antibody levels can reflect disease activity, repeat testing is common; by contrast, a single anti-RBP antibody determination is thought to suffice for clinical purposes. Experience from clinical trials of novel therapies has provided a new perspective on ANA expression during disease, as many patients with SLE are ANA negative at screening despite previously testing positive. Because trial results suggest that patients who are ANA negative might not respond to certain agents, screening strategies now involve ANA and anti-DNA antibody testing to identify patients with so-called ‘active, autoantibody-positive SLE’. Evidence suggests that ANA responses can decrease over time because of the natural history of disease or the effects of therapy. Together, these findings suggest that, during established disease, more regular serological testing could illuminate changes relevant to pathogenesis and disease status. Antinuclear antibodies (ANAs), characteristic features of systemic lupus erythematosus (SLE), are a requirement for disease classification and trial enrolment. In this Review, the authors re-examine the role of ANAs in SLE and discuss changing attitudes towards using ANAs as biomarkers. Antinuclear antibodies (ANAs) bind DNA, RNA and complexes of nucleic acids and protein. In addition to ANAs, anti-DNA and anti-Sm antibodies are part of the classification criteria for systemic lupus erythematosus (SLE). Anti-DNA antibodies and antibodies that recognize RNA-binding proteins show distinct patterns of expression that relate to their origin from different B cell populations. ANAs can mediate events in the pathogenesis of SLE as either free antibodies or as immune complexes. Amounts of ANAs in patients with SLE can change over time as a result of the natural history of the disease or the effects of immunosuppressive agents. Rescreening of ANA levels after disease onset could provide important information about disease mechanisms and disease status. Antinuclear antibodies (ANAs) bind DNA, RNA and complexes of nucleic acids and protein. In addition to ANAs, anti-DNA and anti-Sm antibodies are part of the classification criteria for systemic lupus erythematosus (SLE). Anti-DNA antibodies and antibodies that recognize RNA-binding proteins show distinct patterns of expression that relate to their origin from different B cell populations. ANAs can mediate events in the pathogenesis of SLE as either free antibodies or as immune complexes. Amounts of ANAs in patients with SLE can change over time as a result of the natural history of the disease or the effects of immunosuppressive agents. Rescreening of ANA levels after disease onset could provide important information about disease mechanisms and disease status.