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Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. May 2005; 64(5): 743–749.
Published online Sep 30, 2004. doi:  10.1136/ard.2004.025502
PMCID: PMC1755497

Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial fluid from patients with inflammatory arthritis

Abstract

Background: In K/BxN mice, anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are arthritogenic, and their transfer into naïve mice induces arthritis. Anti-GPI Abs develop in many human patients with RA and are associated with more severe forms of the disease.

Objective: To elucidate the serum and synovial fluid (SF) anti-GPI IgG profiles among different patient groups with a variety of arthritides.

Methods: Blood and SF obtained concomitantly from 91 patients with clinically well defined arthritis were tested for concentrations of total anti-GPI IgG, anti-GPI IgG subclasses, B lymphocyte stimulator (BLyS), and APRIL by ELISA.

Results: Anti-GPI IgG was detected in sera and SF of patients with many arthritic diseases, but was preferentially associated with inflammatory arthritis, in general, and RA, in particular. The anti-GPI IgG subclass usage was skewed and varied among the different arthritic disease groups. Inverse correlations between serum levels of BLyS and anti-GPI IgG and positive correlations between serum levels of APRIL and anti-GPI IgG were seen among immune based arthritic patients and patients with RA but not among non-immune based patients. No correlations were found in SF from any group of arthritic patients.

Conclusion: Raised circulating anti-GPI Abs are not unique to patients with RA but are present in many patients with inflammatory arthritis. The difference in anti-GPI IgG subclass usage among disease groups may influence effector function and disease outcome. The inverse correlation between serum BLyS and anti-GPI IgG levels suggests that anti-GPI B cells may be regulated differently from other autoantibody producing B cells. Anti-GPI Abs may serve a pathogenic function in humans by promoting the maintenance of existing disease.

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Selected References

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Figures and Tables

Figure 1
 Anti-GPI-specific IgG purified from the serum of a patient with RA with high anti-GPI titre. (A) Samples from different purification steps, including the RA serum before purification, the purified total IgG fraction, and the purified anti-GPI ...
Figure 2
 Anti-GPI IgG concentration in sera and SF of patients with various arthritic diseases. Sera (A) and SF (B) obtained concomitantly from 37 patients with RA, 13 with OA, 6 with Tr, 14 with crystal induced arthritis (Crys), 11 with seronegative ...
Figure 3
 Distinct anti-GPI IgG subclass composition observed for patients with different arthritic diseases. Serum samples from 37 patients with RA, 12 with OA, 12 with Crys, 6 with Reiter's syndrome, and 21 healthy subjects (NS) were tested for binding ...
Figure 4
 Correlation between BLyS or APRIL levels and anti-GPI IgG concentration in serum and SF samples of arthritic patients. Correlations representing all 91 patients with arthritis (A-D), only patients with immune based arthritis (E-H), or only patients ...
Figure 5
 Correlation between RF and BLyS, APRIL, or anti-GPI IgG levels in serum of patients with RA. Serum RF values plotted against serum BLyS (A), serum APRIL (B), and serum anti-GPI IgG (C) for the patients with RA for whom concurrent serum BLyS ...

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