Background/Purpose:

Patients with granulomatosis with polyangiitis (GPA) are prone to disease relapse. Changes in anti-neutrophil cytoplasmic autoantibodies (ANCA) levels can predict relapses in individual patients to some extent. Plasmablasts are considered precursors of ANCA-producing plasma cells and are therefore expected to be involved in GPA. This study aimed to determine whether patients at risk for relapse could be distinguished based on increased plasmablast frequency during remission.

Methods:

90 proteinase 3 (PR3)-ANCA positive GPA patients in remission were monitored for relapses for up to 6.3 years. Moreover, 48 healthy controls (HCs) were included. The B cell phenotype was determined at inclusion by flow cytometry, serum ANCA levels were measured with both indirect immunofluorescence and the Phadia ImmunoCAP 250 analyzer. Spontaneous and stimulated in vitro PR3-ANCA production by isolated PBMCs, after 12-day stimulation with or without CpG-ODN, BAFF and IL-21 was measured with Phadia ImmunoCAP 250 analyzer. The frequency of plasmablasts at inclusion of future-relapsing (F-R) and non-relapsing patients (N-R) was compared and the median frequency of plasmablasts was related to relapse-free survival.

Results:

27 of the 90 patients (30%) relapsed after on average 1.64 years (median: 1.75; range: 0.07-3.78) since inclusion. The median frequency of circulating plasmablasts was significantly increased in F-R patients (median: 2.39%, range: 0.6-16.3%) compared to N-R patients (p=0.0014, median: 1.03%, range: 0.1-12.5%) and HCs (p=0.0208, median: 1.33%, range: 0.5-7.6%). The actuarial survival analysis showed a higher percentage of plasmablasts at inclusion was related to decreased relapse-free survival during follow-up (p<0.0001). 70% of the patients with ≥2.39% plasmablasts eventually experienced a relapse during study follow-up compared to 19% in the <2.39% plasmablast group. At inclusion, no significant correlation was found between plasmablast frequency and ANCA titer, serum PR3-ANCA or in vitro PR3-ANCA production.

Conclusion:

Our data suggest that an increased plasmablast frequency during remission is related to a higher frequency of disease relapses in GPA patients. However no correlation with ANCA levels was found. In conclusion, plasmablast frequency might be a helpful biomarker to identify patients in remission at risk for relapse.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-cd38hicd27-plasmablast-frequency-in-remission-predicts-relapsing-disease-in-granulomatosis-with-polyangiitis-patients/