Scleroderma Autoantibodies in Guiding Monitoring and Treatment Decisions

Shivani Shah; Christopher P. Denton


Curr Opin Rheumatol. 2022;34(6):302-310. 

In This Article

Abstract and Introduction


Purpose of Review: One of the key clinical challenges of systemic sclerosis (SSc) is diversity in clinical presentation, organ involvement and disease progression. Antinuclear autoantibodies (ANA) are central to the diagnosis of SSc. ANA specificities associated with distinct clinical patterns of organ and skin involvement. Understanding of the molecular differences and pathogenesis of scleroderma has helped further inform clinical acumen. Here, we provide an update on ANA on clinical profiling, management and future direction of SSc.

Recent Findings: There has been further development in delineating clinical patterns in ANA, genetic susceptibility and antigen triggers predisposing to ANA subtypes. Sub-group analysis of recent clinical trials shows differing treatment responses to novel therapeutics.

Summary: ANA subtyping is likely to be firmly embedded into future classification systems. Beyond informing current management and monitoring of scleroderma patients, ANA subsets have implication on future research and clinical trial design.


Systemic sclerosis (SSc) is an autoimmune condition with substantial clinical and serological heterogeneity. Antinuclear autoantibodies (ANA) are a spectrum of autoantibodies that react with various nucleolar and cytoplasmic components of normal human cells. They are integral to scleroderma the diagnosis, subtype classification, and prognostic evaluation. ANA are present in 90% of scleroderma patients.[1]

The 'classical' ANA subtypes in SSc are the anticentromere antibodies (ACA), antitopoisomerase-1 antibodies (ATA; anti-Scl-70), anti-RNA polymerase III antibodies (ARA). Collectively, these antibodies are found in 50–80% of scleroderma patients.[2,3] ANA associated with SSc are mutually exclusive and specific for SSc. Antibodies associated with scleroderma overlap syndromes, such as anti-Pml/Scl and anti-Ku are less specific for scleroderma but remain mutually exclusive.[3] Patients do not switch ANA subset type throughout their disease duration.

Over the recent years, advances in collaborative practice and genetic analysis have further improved our understanding of these distinct clinical patterns. This review focuses on the principal differences in ANA profiles, mechanisms of pathogenicity, and impact on management.