Autoantibodies in the disease criteria for systemic sclerosis: The need for specification for optimal application

The ACR/EULAR classification criteria for systemic sclerosis (SSc) entail three autoantibodies: anti-centromere antibodies (ACA), anti-topoisomerase I antibodies (ATA), and anti-RNA-polymerase III antibodies (ARA). The importance of ACA and ATA in the classification criteria is evidence based, but the diagnostic value is overestimated by clinicians. Fortunately, these autoantibodies are characterized by good agreement between different immuno-assays. Inclusion of ARA, however, is based on limited evidence and is related to limited agreement between different immuno-assays. Harmonization of immuno-assays in terms of interpretation based on likelihood ratio's may improve future classification criteria for SSc and this needs to be achieved by close collaboration between clinicians, laboratory specialists and the diagnostic industry.

Automated summary

The classification criteria for systemic sclerosis (SSc) by ACR/EULAR includes three autoantibodies: anti-centromere antibodies (ACA), anti-topoisomerase I antibodies (ATA), and anti-RNA-polymerase III antibodies (ARA). The importance of ACA and ATA is well-supported by evidence, although their diagnostic value is overestimated by clinicians. These autoantibodies, fortunately, show good agreement across different immuno-assays. However, the inclusion of ARA is based on limited evidence and there is limited agreement across different immuno-assays. Harmonization of immuno-assays through likelihood ratio-based interpretation may improve future SSc classification criteria, requiring close collaboration between clinicians, laboratory specialists, and the diagnostic industry.