Anti-PDGFR-α antibodies measured by non-bioactivity assays are not specific for systemic sclerosis

Objective:To evaluate the presence of anti-PDGFR-α antibodies by immunological methods in patients with systemic sclerosis (SSc).Methods:Fifty-eight women diagnosed with SSc and 36 healthy women controls were included. IgG anti-PDGFR-α were measured by ELISA and immunoblot. Associations with clinical and immunological findings were also studied.Results:Non-significant differences were detected between patients with SSc and controls: median value 0.287 (range 0–2.06) versus median value 0.226 (range 0–2.94), respectively (p = 0.583). No correlation between the presence of anti-PDGFR-α antibodies and clinical and serological features was found. Serum samples from patients with SSc and healthy people who had high titres of anti-PDGFR-α antibodies by ELISA recognised the same band corresponding to PDGFR-α by immunoblot.Conclusion:Although anti-PDGFR-α antibodies seem to be disease-specific when determined by bioactivity assays, these antibodies are also detected in normal subjects when immunological methods are used. Thus, anti-PDGFR-α antibodies may arise from natural autoantibodies. Possibly, SSc autoantibodies recognise a different epitope on the PDGFR-α molecule which triggers its stimulatory effect when analysed by functional assays. Alternatively, naturally occurring autoantibodies may even become pathogenic after affinity maturation and class switching in genetically susceptible subjects.