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Rheumatic Disease Differentiation Using Immunoglobulin G Sugar Printing by High Density Electrophoresis

JOHN S. AXFORD, GAYE CUNNANE, OLIVER FITZGERALD, J. MARTIN BLAND, BARRY BRESNIHAN, and EMMA R. FREARS

ABSTRACT.

Objective.
To determine whether immunoglobulin G (IgG) sugar printing using high density electrophoresis can be a diagnostic and prognostic test to rapidly differentiate early rheumatoid arthritis (ERA), rheumatoid arthritis (RA), and other rheumatic diseases from each other.

Methods. One hundred fifty-three patients with ERA/RA, psoriatic arthritis (PsA), early psoriatic arthritis (EPsA) ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), early undifferentiated seronegative arthritis (UA), and osteoarthritis (OA) were investigated. Samples of their serum IgG were purified, and sugars were released enzymatically and fluorophore-labelled, then subjected to high density electrophoresis, and relative quantities of each sugar were determined by optical density.

Results. Sugar prints of 9 sugars were compiled for each of the 9 disease groups. Specific disease-associated sugar changes were determined by comparison with OA. For example, agalactosylated structures were increased in ERA/RA and EPsA/PsA (p = 0.0001–0.004) and digalactosylated structures were decreased in PsA, AS, and JIA (p = 0.0001–0.04). When the disease groups were compared, each disease was characterized by a unique sugar print comprising 7 of the 9 sugars (p = 0.001–0.005); only g0fb and a1f were not associated. ERA/RA differed in the quantities of monogalactosyl and sialylated sugars (p = 0.006–0.007). The presence of agalactosyl sugars enabled correct prediction of RA in 71.2% of individuals, with a specificity of 84.2% and sensitivity of 50.0%. The area under the sensitivity versus specificity curve was 0.7812.

Conclusion. IgG sugar printing was found to be effective in differentiation of rheumatic diseases and can differentiate ERA and RA from each other and from other rheumatic diseases; and hence may constitute a relatively rapid diagnostic and prognostic test for patients presenting with arthritis. (J Rheumatol 2003;30:2540-6)

Key Indexing Terms:

RHEUMATIC DISEASE
IMMUNOGLOBULIN G
SUGARS
ELECTROPHORESIS
EARLY ARTHRITIS


From the Academic Unit of Musculoskeletal Disease and Department of Public Health Sciences, St. George's Hospital Medical School, London, England; and Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland.

J.S. Axford, MD, FRCP; G. Cunnane, MRCP(I); J.M. Bland, PhD; E.R. Frears, PhD, St. George's Hospital Medical School; O. FitzGerald, MD, FRCP(I), FRCP; B. Bresnihan, MD, FRCP(I), FRCP, St. Vincent's University Hospital.

Address reprint requests to Dr. J.S. Axford, Academic Unit for Musculoskeletal Disease, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. E-mail: j.axford@sghms.ac.uk

Submitted August 12, 2002; revision accepted April 23, 2003.




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