Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Differential Serum Glycosylation Changes in Rheumatoid and Psoriatic ArthritisIn Response to Anti-TNF Therapy.

Alavi1,  Azita, FitzGerald3,  Oliver M., Collins4,  Emily S., Fraser2,  Owen, Tarelli1,  Edward, Ng4,  Chin Teck, Bresnihan5,  Barry

St. Georges University of London, United Kingdom
St. Georges University of London, United Kingdom
St. Vincent's University Hospital, Dublin, Ranelagh Dublin, Ireland
St. Vincent's University Hospital, Dublin, Ireland
St. Vincent's University Hospital, Dublin, Ireland

Background:

Our earlier research into IgG glycosylation changes associated with rheumatoid arthritis (RA) and other rheumatic diseases has indicated the presence of disease specific glycosylation profiles, which in the case of RA have been shown to correlate with disease activity and to revert to normal in pregnancy induced remission. We have since extended these studies using whole serum to assess the direct diagnostic and prognostic potential of serum sugar biomarkers.

Objectives:

Evaluate the influence of anti-TNFa therapy on the serum N-glycosylation profile of RA and psoriatic arthritis (PsA) patients and to assess the potential of these sugar biomarkers as a measure of disease response.

Methods:

Serum N-glycan profile of a cohort of RA (n=24) and PsA (n=18) patients on anti-TNFa therapy, at baseline and 1 year after starting treatment, were investigated. Enzyme released N-glycans were analysed by MALDI-TOF mass spectrometry. Direct comparisons of the sugar profiles (mass / charge ratio) indicated significant changes in the profile of several biantennary N-glycan structures; distinguished by the presence / absence of galactose (G), fucose (F), bisecting GlcNAc (bis) and sialic acid (A) attached to the core biantennary heptasaccharide [GlcNAc(b1–2)Man(a1–6)][GlcNAc(b1–2)Man(a1–3)]-Man(b1–4)GlcNAc(b1–4)GlcNAc. The glycans comprised of G0 (non-galactosylated), G2F (fucosylated di-galactosylated), A1G2F (mono-sialylated G2F), A2 (di- sialylated G2) and A2bisF (fucosylated di-sialylated G2 with a bisecting N-acetylglucosamine).

Results:

RA and PsA were found to have distinct serum glycan profiles, which underwent significant changes in response to treatment with anti-TNFa (Figure). Levels of G0 decreased significantly in both RA (p=0.012) and PsA (p=0.028). This was accompanied by a moderate, but significant, increase in A1G2F (RA; p=0.018 and PsA; p=0.010).

Anti-TNFa treatment also resulted in significant increase (19–20%; p<0.05) in the levels of other glycan structures; G2F and A2G2 in RA, and A2G2bisF in PsA. The G2F glycan values were found to significantly correlate with changes in diseases activity (DAS-28) in RA patients (n=24) after one year of anti-TNFa therapy(Pearson; r (22)=0.421>p>0.04).

Interestingly, there were also marked differences between Etanercept and Adalimumab, with the RA Adalimumab treated group showing significantly more pronounced changes in G0 and A2 (PsA cohort too small for analysis).

Conclusion:

RA and PsA have distinct serum N-glycan profiles which undergo significant changes in response to anti-TNFa therapy. These differential changes which include galactosylation as well as sialylation could be a useful marker of disease response, and may provide a better insight into the different mechanistic action of TNF antagonists currently used for treatment of inflammatory arthritis.

To cite this abstract, please use the following information:
Alavi, Azita, FitzGerald, Oliver M., Collins, Emily S., Fraser, Owen, Tarelli, Edward, Ng, Chin Teck, et al; Differential Serum Glycosylation Changes in Rheumatoid and Psoriatic ArthritisIn Response to Anti-TNF Therapy. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1105
DOI: 10.1002/art.28872

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