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

Lee, David and Nigrovic, Peter (2012) Hypogalactosylation of IgG fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis. Arthritis Research and Therapy, 14 (2). R43. ISSN 1478-6354


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<0.05 for each cohort). However, pre-treatment sG0/G1 was not predictive of clinical response to treatment. Change in sG0/G1 was similar in MTX and TNF inhibitor groups. Corrected for disease activity, ACPA positivity correlated with higher sG0/G1 values.
Conclusions: Baseline IgG hypogalactosylation did not distinguish patients likely to experience a favorable clinical response to MTX or TNF blockade. Clinical improvement correlated with partial normalization of IgG glycosylation. ACPA was associated with more aberrant IgG glycosylation.

Item Type: Article
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Additional Information: The work/data contained in this manuscript was performed at my previous position at Brigham and Women's Hospital/Harvard Medical School Can archive pre-print and post-print or publisher's version/PDF
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15


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