Background/Purpose: B-cells play a pivotal role in the initiation and perpetuation of systemic lupus erythematosus (SLE). Recently, it has been demonstrated that in active SLE patients, the peripheral blood is enriched in CD27⁺IgD^– post-switched memory B-cells. The aim of our study was to delineate the B-cell repertoire of SLE patients with low disease activity (SLEDAI – 2K ≤4).

Methods: Peripheral blood samples from 42 patients suffering from SLE (mean±SD; age 42±13 years, 88% females, disease duration 10.9±7 years) and 74 age-matched healthy controls (HC; age 46±17 years, 80% female) were drawn over 2 years. All SLE patients were in remission or with low disease activity (SLEDAI of 2.0±1.7) achieved with different therapies, e.g. rituximab (RTX), cyclophosphamide, hydroxychloroquine or mycophenolate. B-cells were characterized using CD19^–, CD20^–, CD5^–, CD27^– antibodies and grouped in naïve (IgD⁺27^–), non-switched memory (IgD⁺, CD27⁺), memory (IgD^-, CD27⁺), B1 (CD5⁺27^–) and MBL-like (CD5⁺⁺) B-cells. A quantitative flow cytometric bead-based assay (QuantiBRITE PE kit from Becton Dickinson) was used for the estimation of CD19 antibodies bound per cell. All cytometric measurements were performed using a standardized BD LSR Fortessa platform.

Results: SLE patients had significantly higher B1 type B-cells in comparison with HC (median±SE, 16.8±2.1% vs. 9.9±0.7%; p=0.001). In addition, naïve and MBL type B-cells were significantly more frequent (p< 0.005) in patients with SLE than in HC (77.2±3.6% vs. 61.6±1.4%; 0.3±0.1 vs.0.2±0.1; respectively). In contrast, memory and marginal zone B-cells were significantly reduced (p=0.001) in SLE patients with low disease activity (10.2±1.8% vs.16.6±1.0%; 2.9±0.9% vs. 9.9±0.7%; respectively). Interestingly, also non-switched memory B-cells were significantly lower in SLE patients compared to HC (2.1±0.7% vs. 6.5±0.5%; p< 0.0001). No significant difference was seen for the number of CD19 molecules on the surface of B-cells of SLE patients or HC (7432±449 vs. 7900±225; respectively). In addition, the percentage of CD86+ B-cells capable of activating T-cells were similar between SLE patients and HC (9.3±1.1% vs.8.4 ± 0.4%; p =0.421).

Conclusion: Patients with low SLE activity show an increase of naïve and inactive B-cells. This is true for patients treated successfully with RTX, cyclophosphamide and also for SLE patients treated with mycophenolate and hydroxychloroquine.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/diminished-memory-b-cells-in-systemic-lupus-erythematosus-patients-with-low-disease-activity/