Background/Purpose
Patients with granulomatosis with polyangiitis (GPA) suffer from frequent disease relapses, with up to 50% of patients relapsing within 5 years. Several risk factors for relapse have been described, such as persistent ANCA titers and Staphylococcus aureus nasal carriage. However, no method to predict a relapse in individual patients is currently known. Changes in measures that reflect the pathogenic process in the patient may be useful to improve relapse prediction in these patients.
Methods
Forty-nine patients with GPA were monitored for a period of 8-16 months, with 3-7 sampling moments for each patient. At each time point peripheral blood mononuclear cells were cultured in presence of CpG-oligodeoxynucleotides, B-cell activating factor and interleukin-21 for 12 days. Subsequently supernatants were analysed for PR3-ANCA by Phadia EliA, results being expressed in response units (RU), and production of total IgG was assessed by ELISA. Moreover, ANCA titers were determined by immunefluorescence. B cell phenotypes were analysed by using flow cytometry on whole blood stained for CD19, CD24, CD27 and CD38. With these markers percentages and total numbers of B cells were determined, and naive, transitional, memory and regulatory B cells were distinguished. Median values from the last measured time point before relapse were compared to non-relapsing patients. For non-relapsing patients the average value of all time points measured was used. All patients were also scored based on their inclusion sample and subsequently analyzed for differences in disease-free survival.
Results
During follow-up 12 patients relapsed. Patients that relapsed showed higher median values of in vitro PR3-ANCA (9.1 RU vs 2.2 RU) as well as higher ANCA titers compared to the non-relapsing patients. The higher levels of PR3-ANCA IgG were not a reflection of higher total IgG production, levels of IgG were in fact decreased in patients before relapse. Three patients relapsed directly after the inclusion sample, two of which showed >15 RU of in vitro PR3-ANCA. Of the remaining nine patients, six were positive for PR3-ANCA, and also showed an increase in this measure prior to relapse. Patients that had >2 RU of in vitro PR3-ANCA at inclusion showed lower disease-free survival, while no such difference was observed for ANCA titer or total IgG. The median percentages of memory and regulatory B cells, both CD24hiCD38hi and CD24hiCD27+ , were lower in patients prior to relapse. However, no differences in disease-free survival were observed when patients were divided based on percentage at inclusion. When analyzing the absolute numbers of B cell subsets patients with low numbers of CD27+ memory B cells at inclusion were shown to be more prone to relapse.
Conclusion
This study shows a few promising factors to assist in the prediction of relapse in GPA patients, most notably in vitro ANCA production. Finding a better predictive factor for relapse in GPA would allow for timely intervention and possibly prevention of relapse in patients. Currently 80 PR3-ANCA positive GPA patients are being monitored with this method to strengthen these data.
Disclosure:
J. Land,
None;
W. H. Abdulahad,
None;
C. A. Stegeman,
None;
P. Heeringa,
None;
A. Rutgers,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/predicting-relapse-in-patients-with-granulomatosis-with-polyangiitis-the-potential-use-of-monitoring-in-vitro-anca-production/