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Baseline IgG-Fc N-glycosylation profile is associated with long-term outcome in a cohort of early inflammatory arthritis patients. | LitMetric

AI Article Synopsis

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease, and predicting its long-term outcome early on is challenging; IgG and its glycosylation patterns play a significant role in inflammation associated with RA.
  • A study analyzed IgG Fc glycopeptides from the sera of 118 untreated early inflammatory arthritis patients, looking for associations between these glycoforms and disease prognosis after 2 years of treatment.
  • The results indicated that specific levels of IgG2/3 Fc galactosylation were linked to better outcomes after 2 years, suggesting that IgG glycosylation could be a potential new prognostic marker for early arthritis, pending further validation in larger studies.*

Article Abstract

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease for which prediction of long-term prognosis from disease's outset is not clinically feasible. The importance of immunoglobulin G (IgG) and its Fc N-glycosylation in inflammation is well-known and studies described its relevance for several autoimmune diseases, including RA. Herein we assessed the association between IgG N-glycoforms and disease prognosis at 2 years in an early inflammatory arthritis cohort.

Methods: Sera from 118 patients with early inflammatory arthritis naïve to treatment sampled at baseline were used to obtain IgG Fc glycopeptides, which were then analyzed in a subclass-specific manner by liquid chromatography coupled to mass spectrometry (LC-MS). Patients were prospectively followed and a favorable prognosis at 2 years was assessed by a combined index as remission or low disease activity (DAS28 < 3.2) and normal functionality (HAQ ≤ 0.25) while on treatment with conventional synthetic DMARDs and never used biologic DMARDs.

Results: We observed a significant association between high levels of IgG2/3 Fc galactosylation (effect 0.627 and adjusted p value 0.036 for the fully galactosylated glycoform H5N4F1; effect -0.551 and adjusted p value 0.04963 for the agalactosylated H3N4F1) and favorable outcome after 2 years of treatment. The inclusion of IgG glycoprofiling in a multivariate analysis to predict the outcome (with HAQ, DAS28, RF, and ACPA included in the model) did not improve the prognostic performance of the model.

Conclusion: Pending confirmation of these findings in larger cohorts, IgG glycosylation levels could be used as a prognostic marker in early arthritis, to overcome the limitations of the current prognostic tools.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404591PMC
http://dx.doi.org/10.1186/s13075-022-02897-5DOI Listing

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