Hypogalactosylation of IgG fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis

Objectives: Hypogalactosylation of IgG is associated with rheumatoid arthritis (RA). We examined whether baseline IgG glycan status predicts response to therapy, and whether methotrexate (MTX) and TNF blockade differentially impact IgG galactosylation. Methods: Using a previously-defined high-throughput approach, we ascertained the galactosylation status of circulating IgG in two well-defined RA clinical cohorts, ABCoN (n = 98) and Nested I (n = 64). The ratio of agalactosylated to monogalactosylated IgG in serum (sG0/G1) was determined before and during therapy with MTX or TNF inhibition, and correlated with clinical response as assessed by DAS28-CRP and EULAR response criteria. Results: RA patients from both cohorts exhibited the expected elevation of sG0/G1 at baseline. Improvement in clinical scores correlated with a reduction in sG0/G1 (Spearman ρ= 0.31-0.37, P