Hypogalactosylation of serum N-glycans fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis

Hdl Handle:
http://hdl.handle.net/10147/218251
Title:
Hypogalactosylation of serum N-glycans fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis
Authors:
Ercan, Altan; Cui, Jing; Hazen, Melissa M; Batliwalla, Franak; Royle, Louise; Rudd, Pauline M; Coblyn, Jonathan S; Shadick, Nancy; Weinblatt, Michael E; Gregersen, Peter; Lee, David M; Nigrovic, Peter A
Citation:
Arthritis Research & Therapy. 2012 Mar 05;14(2):R43
Issue Date:
5-Mar-2012
URI:
http://dx.doi.org/10.1186/ar3756; http://hdl.handle.net/10147/218251
Abstract:
Abstract Introduction Rheumatoid arthritis (RA) is associated with hypogalactosylation of immunoglobulin G (IgG). We examined whether a proxy measure for galactosylation of IgG N-glycans could predict response to therapy or was differentially affected by methotrexate (MTX) or TNF blockade. Methods Using a previously defined normal phase high-performance liquid chromatography approach, we ascertained the galactosylation status of whole serum N-glycans in two well-defined RA clinical cohorts: the Autoimmune Biomarkers Collaborative Network (n = 98) and Nested I (n = 64). The ratio of agalactosylated to monogalactosylated N-glycans in serum (sG0/G1) was determined before and during therapy with MTX or TNF inhibition and correlated with anticitrullinated peptide antibody (ACPA) status and clinical response as assessed by 28-joint Disease Activity Score utilizing C-reactive peptide and European League Against Rheumatism response criteria. Results RA patients from both cohorts exhibited elevation of sG0/G1 at baseline. Improvement in clinical scores correlated with a reduction in sG0/G1 (Spearman's ρ = 0.31 to 0.37; P < 0.05 for each cohort). However, pretreatment sG0/G1 was not predictive of clinical response. Changes in sG0/G1 were similar in the MTX and TNF inhibitor groups. Corrected for disease activity, ACPA positivity correlated with higher sG0/G1. Conclusions Baseline serum N-glycan hypogalactosylation, an index previously correlated with hypogalactosylation of IgG N-glycans, did not distinguish patients with rheumatoid arthritis who were likely to experience a favorable clinical response to MTX or TNF blockade. Clinical improvement was associated with partial glycan normalization. ACPA-positive patients demonstrated enhanced N-glycan aberrancy compared with ACPA-negative patients.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorErcan, Altan-
dc.contributor.authorCui, Jing-
dc.contributor.authorHazen, Melissa M-
dc.contributor.authorBatliwalla, Franak-
dc.contributor.authorRoyle, Louise-
dc.contributor.authorRudd, Pauline M-
dc.contributor.authorCoblyn, Jonathan S-
dc.contributor.authorShadick, Nancy-
dc.contributor.authorWeinblatt, Michael E-
dc.contributor.authorGregersen, Peter-
dc.contributor.authorLee, David M-
dc.contributor.authorNigrovic, Peter A-
dc.date.accessioned2012-04-12T08:23:10Z-
dc.date.available2012-04-12T08:23:10Z-
dc.date.issued2012-03-05-
dc.identifier.citationArthritis Research & Therapy. 2012 Mar 05;14(2):R43-
dc.identifier.urihttp://dx.doi.org/10.1186/ar3756-
dc.identifier.urihttp://hdl.handle.net/10147/218251-
dc.description.abstractAbstract Introduction Rheumatoid arthritis (RA) is associated with hypogalactosylation of immunoglobulin G (IgG). We examined whether a proxy measure for galactosylation of IgG N-glycans could predict response to therapy or was differentially affected by methotrexate (MTX) or TNF blockade. Methods Using a previously defined normal phase high-performance liquid chromatography approach, we ascertained the galactosylation status of whole serum N-glycans in two well-defined RA clinical cohorts: the Autoimmune Biomarkers Collaborative Network (n = 98) and Nested I (n = 64). The ratio of agalactosylated to monogalactosylated N-glycans in serum (sG0/G1) was determined before and during therapy with MTX or TNF inhibition and correlated with anticitrullinated peptide antibody (ACPA) status and clinical response as assessed by 28-joint Disease Activity Score utilizing C-reactive peptide and European League Against Rheumatism response criteria. Results RA patients from both cohorts exhibited elevation of sG0/G1 at baseline. Improvement in clinical scores correlated with a reduction in sG0/G1 (Spearman's ρ = 0.31 to 0.37; P < 0.05 for each cohort). However, pretreatment sG0/G1 was not predictive of clinical response. Changes in sG0/G1 were similar in the MTX and TNF inhibitor groups. Corrected for disease activity, ACPA positivity correlated with higher sG0/G1. Conclusions Baseline serum N-glycan hypogalactosylation, an index previously correlated with hypogalactosylation of IgG N-glycans, did not distinguish patients with rheumatoid arthritis who were likely to experience a favorable clinical response to MTX or TNF blockade. Clinical improvement was associated with partial glycan normalization. ACPA-positive patients demonstrated enhanced N-glycan aberrancy compared with ACPA-negative patients.-
dc.titleHypogalactosylation of serum N-glycans fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderErcan et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2012-04-11T11:02:06Z-
All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.