AB0090 BASELINE IgG-Fc N-GLYCOSYLATION PROFILE IS ASSOCIATED WITH LONG-TERM OUTCOME IN A COHORT OF EARLY INFLAMMATORY ARTHRITIS PATIENTS

Abstract

BackgroundRheumatoid arthritis (RA) is a systemic autoimmune disease which causes chronic joint inflammation and functional limitation1,2. The diagnosis of rheumatoid arthritis (RA) is mainly based on clinical data and RA specific autoantibodies, while the prediction of long-term prognosis from disease outset is not clinically reliable3,4. The importance of immunoglobulin G (IgG) and its Fc N-glycosylation in inflammation of RA has been described, with changes in the glycosylation profiles observed years before the diagnosis of RA5.ObjectivesWe herein sought to assess the value of total serum IgG Fc N-glycosylation as a diagnostic and prognostic biomarker in patients with early inflammatory arthritis (EIA). Specifically, we aim to assess whether IgG N-glycoform levels may predict the diagnosis of RA or undifferentiated arthritis (UA) and the long-term disease‘s outcome in patients with EIA arthritis patients naïve to treatment.MethodsThe “Early Arthritis Clinic” of the University Hospital of Heraklion is a prospective cohort of patients with inflammatory arthritis. For the present study, we selected a group of patients naïve to any immunosuppressive treatments with available serum at baseline evaluation (n=118). At baseline, demographics, RA clinical characteristics (DAS28, HAQ-DI) and laboratory tests [autoantibodies (RF and/or ACPA)], were also recorded. The patients were prospectively followed for two years, with clinical, laboratory and disease-related treatments documented. A diagnosis of RA or UA was based on established classification criteria6. In order to assess long-term prognosis we formulated a combined “index” of favourable outcome if the patients fulfilled all the following at 24 months of follow-up: remission or low disease activity (based on DAS28 < 3.2) and normal functionality (based on HAQ ≤ 0.25) while on treatment with csDMARDs and never use bDMARDs. We applied a state-of-the-art liquid chromatography - mass spectrometry (LC-MS) based workflow for analysis of subclass-specific IgG Fc N-glycosylation at the baseline7.ResultsWe studied 118 EIA patients [age (mean, SD) (53, 15.6) years, females (80.5%), symptoms duration (53.8, 8.7) years, ACPA positive (16%), DAS28 (4.8, 0.14)]. During the 2 years of follow-up, 60% of the patients were diagnosed with RA and 40% with UA. Although patients with UA had higher relative abundances of galactosylated and sialylated N-glycoforms (H4N4F1, H5N4F1 and H5N4F1S1) in all IgG subclasses at baseline compared to RA patients, differences were not statistically important. Interestingly, we observed a significant association between high levels of IgG2/3 galactosylation for H5N4F1 [effect 0.63, adjusted p=0.036)] and H3N4F1 [effect -0.55122, adjusted p=0.0496) and favorable outcome after two years of treatment.ConclusionIn our cohort of EIA we found IgG2/3 Fc N-glycoforms to be associated with a favorable prognosis after 2 years of follow-up. Should the present data be confirmed in a larger cohort could be of clinical value. Since currently available prognostic tools have significant limitations, further research should aim to the development of a predictive tool of high specificity and sensitivity based on the combination of clinical, serological data and novel biomarkers.