Background/Purpose:   GP88 (progranulin; PGRN) is a glycoprotein with a molecular weight of approximately 88,000 Da and is thought to play an important role in immune response and tumor proliferation, among other functions. An increasing number of studies have examined anti-inflammatory effect of GP88 in autoimmune diseases. We also reported that GP88 may become a new molecular biomarker for rheumatoid arthritis (RA) (Inflammation 37:1806-13, 2014). We examined the correlation between the efficacy of infliximab (IFX) and serum GP88 concentration in RA patients treated with IFX.

Methods:   First, we measured the concentration of GP88 by using ELISA in the serum of 101 RA patients who met the 2010 ACR/EULAR classification criteria and 75 patients with undifferentiated arthritis (UA) prior to starting treatment, who were being treated at a specialist rheumatology outpatient clinic, and compared the results with those from the serum of 149 (men n = 78, women n = 71) healthy individuals undergoing medical check-ups as the control group. Next, we measured GP88 concentration during IFX treatment (start of administration was set as the baseline, and measurements were taken at 14 weeks and 52 weeks or at the time when IFX was discontinued or the dose was changed) by using the frozen stored serum of 50 RA patients who received IFX and were unresponsive to methotrexate.

Results:   The GP88 concentration in healthy individuals was 40.5 ± 14.3 ng/mL in men (25–68 years: mean 54.2 years) and 41.0 ± 10.9 ng/mL in women (28–69 years: mean 51.0 years), and there were no gender or age differences. The GP88 concentration was 65.7 ± 2.72 ng/mL in RA patients and 57.4 ± 1.67 ng/mL in UA patients, indicating significantly higher levels in RA patients compared to those in UA patients (p < 0.01) and healthy individuals (p < 0.001). The background of RA patients treated with IFX was women, n = 40; men, n = 10; aged 26–81 years; mean 60.3 years. The oral methotrexate dose was 6–16 mg/week and IFX dose was 3 mg/kg. The GP88 concentration (mean value) for all 50 patients at each measurement point was baseline: 63.5 ng/mL; 14 weeks: 65.5 ng/mL; and 52 weeks: 69.7 ng/mL. These results indicate an increasing trend, but there were no significant fluctuations. Upon classification of the groups based on IFX efficacy [effective n = 25 (patients continuing IFX treatment at 52 weeks), primary failure n = 4 (ineffective from the beginning), secondary failure n = 14 (effect weakened midway through treatment), adverse events n = 7 (patients who stopped treatment owing to development of malignant tumor, reaction at administration, among others)], the mean baseline GP88 concentrations (ng/mL) were 62.8, 48.4, 67.1, and 67.5 respectively. These results showed a low level of efficacy in patients with primary failure and higher levels in patients with secondary failure or adverse events. The mean GP88 concentration was 65.2 ng/mL at 52 weeks in responders, but increased to 82.5 ng/mL in patients with secondary failure when they switched from IFX to another drug.

Conclusion:   Based on these results, measurement of the GP88 concentration may be useful for auxiliary RA diagnosis, predicting the efficacy of IFX in RA patients, and predicting weakening of the effect during treatment.  

ACR Meeting Abstracts - https://acrabstracts.org/abstract/can-gp88-progranulin-be-used-to-predict-the-efficacy-of-infliximab/