Elevated Serum Glucose-6-Phosphate Isomerase Correlates with Histological Disease Activity and Clinical Improvement After Initiation of Therapy in Patients with Rheumatoid Arthritis

Objective. To determine serum glucose-6-phosphate isomerase (GPI) concentrations in patients with rheumatoid arthritis (RA), and to test whether they correlate with objective measures of disease activity. Methods. Sera from 116 patients with RA, 69 patients with non-RA rheumatic diseases, and 101 healthy controls were analyzed. Levels of soluble serum GPI were measured by ELISA. Histological disease activity was determined with the synovitis score in synovial needle biopsies from 58 of the 116 patients with RA. Thirty-one of the 58 synovium samples were stained for CD68, CD3, CD20, CD38, CD79a, and CD34 by immunohistochemistry. Demographic data were collected, as well as serological and clinical variables that indicate RA disease activity, for Spearman correlation analysis. Results. Serum GPI level correlated positively with the synovitis score (r = 0.278, p = 0.034). Significantly higher soluble GPI levels were detected in the RA sera compared with sera from healthy controls and the non-RA disease controls (2.25 +/- 2.82 vs 0.03 +/- 0.05 and 0.19 +/- 0.57 mu g/ml, respectively; p < 0.0001). The rate of serum GPI positivity was significantly higher in the RA patients than in the non-RA disease controls (64.7% vs 10.1%; p < 0.0001). Spearman analysis showed no significant correlation between serum GPI level and Disease Activity Score in 28 joints at baseline. After initiation of antirheumatic treatments, GPI levels decreased significantly (2.81 +/- 3.12 vs 1.44 +/- 2.09 mu g/ml; p = 0.016), paralleling improvement of the disease activity indices. Conclusion. Elevated serum GPI may be involved in the synovitis of RA and may prove useful as a serum marker for disease activity of RA. (First Release September 1 2010; J Rheumatol 2010;12:2452-61; doi:10.3899/jrheum.100157)