Hyper-glycosylation of Anti-Citrullinated Peptide Autoantibodies in Rheumatoid Arthritis

The consortium identified Anti-Citrullinated Peptide Antibodies (ACPA) hyper-glycosylation as marker for the development of the pathogenic autoimmune response underlying Rheumatoid Arthritis (RA). In collaboration with BMS, the consortium studied the utilization of ACPA hyper-glycosylation as diagnostic tool to predict and measure response to therapies in individual patients.

2.3 million Dutch people suffer from rheumatic disorders. For the 150,000 with the most severe form, RA, no cure exists. Currently, 30% of RA patients on biological pharmaceuticals do not respond to treatment. The consortium hopes their project will result in the clinical application of a specific molecular biomarker to be able to predict response to specific biological therapies in the individual patients, ultimately contributing to cost-effective improvements of patient outcomes and quality of life.

In this project, BMS provided serum samples obtained from patients included in a clinical trial on different time points after the start of the treatment. Patients were treated with Methotrexate only, or with Methotrexate in combination with a biological treatment. LUMC measured the glycosylation status of ACPA in the serum samples and the correlation of ACPA hyper-glycosylation from patient-derived samples with different disease characteristics was analysed by BMS.

The study demonstrated that treatment with Methotrexate in combination with a biological treatment affected the hyper-glycosylation status of ACPA compared to treatment with Methotrexate only. This interesting finding motivated the researchers to continue this project to study the capacity of ACPA-glycosylation as diagnostic tool to predict the subgroup of RA patients that will respond to (expensive) biological therapies and monitor the effectiveness of the therapy.