gms | German Medical Science

Introduction: Antibodies provide long-term humoral protection against pathogens. However, antibodies can also contribute to the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) by inciting immune-complex formation driving inflammation. In turn, inflammation can modulate antibody function and pathogenicity, e.g. through changing IgG Fc glycosylation. Generally, in immunoglobulins, glycosylation acts as important regulator of antibody stability and function. IgG Fc glycosylation determines binding to pro- and anti-inflammatory Fcg receptors (FcgR). During infections the production of hyposialylated IgG can improve the defence against pathogens, however, in autoimmunity hyposialylated IgG may propagate inflammation and disease progression. The aim of this study was to determine glycosylation of total IgG and MCV (mutated citrullinated vimentin)-specific IgG in RA patients and to explore the association of the IgG glycosylation status with disease activity.

Methods: In a cohort of 97 and 63 RA patients, sialylation levels of total IgG and of IgG specific for MCV were determined by ELISA. Signs of disease activity (DAS28 and HAQ) as well as changes in the medical records were assessed. Patients were included into the study at first diagnosis or flaring disease (t0) requiring therapy initiation or adaptation. Patients were followed-up in 1–2 successive visits (t1 and t2) at intervals of approximately 6 months.

Results: Our preliminary analyses show an increase in the sialylation of total IgG as well anti-MCV at t1 compared to t0 along with an improvement of disease activity as determined by the DAS28. The increase in IgG sialylation was also observed within subgroups of patients receiving treatment with MTX and abatacept, representing the largest subgroups in this study. Finally, a correlation analysis showed that an increase in IgG- as well as anti-MCV-sialylation is associated with an improved DAS28 disease activity score.

Conclusion: In line with other inflammatory diseases, these data suggest that Ig sialylation may be involved in disease development and progression and may serve as a biomarker for disease activity and treatment response.