Anti-ANP32A antibodies in systemic sclerosis

Numerous studies have identified autoantibody status as an important biomarker of cancer risk around the time of systemic sclerosis (SSc) onset. For example, anti-RNA polymerase III antibody positivity associates with increased cancer risk near SSc onset, while the presence of anticentromere or anti-Th/To antibodies may be protective.1–4 In this context, we selected serum from a well-characterised patient with SSc with squamous cell skin cancer and a short cancer–scleroderma interval to discover cancer-associated autoantibodies. Immunoprecipitations performed with this serum using 624 melanoma cell lysates were subjected to on bead digestion and liquid chromatography tandem mass spectrometry peptide sequencing. This identified antibodies targeting the tumour suppressor gene, acidic leucine-rich nuclear phosphoprotein (ANP32A), which migrates on SDS-polyacrylamide gels at ~28.5 kDa. Antibodies against ANP32A were validated in this serum by immunoprecipitation using 35S-methionine labelled ANP32A generated by in vitro transcription/translation from DNA (Origene) as described.5 To further explore the association between anti-ANP32A antibodies and cancer in patients with SSc, sera from patients with (n=213) and without cancer (n=190) were randomly selected from the Johns Hopkins Scleroderma Center Research Registry for anti-ANP32A antibody testing. The Registry prospectively collects demographic information, cancer diagnoses and longitudinal disease metrics. …