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ObjectiveSystemic lupus is a chronic autoimmune disease characterised by its phenotypic heterogeneity. Neutropaenia is a frequent event in SLE occurring in 20%–40% of patients depending on the threshold value of neutrophil count. On a daily basis, the management of neutropaenia in SLE is difficult with several possible causes. Moreover, the infectious consequences of neutropaenia in SLE remain not well defined.Methods998 patients from the Lupus BioBank of the upper Rhein (LBBR), a large German and French cohort of patients with SLE, mostly of Caucasian origin (83%), were included in this study. Neutropaenia was considered when neutrophil count was below 1800×106/L. An additional analysis of detailed medical records was done for 65 LBBR patients with neutropaenia.Results208 patients with neutropaenia (21%) were compared with 779 SLE patients without neutropaenia. Neutropaenia in SLE was significantly associated with thrombocytopaenia (OR 4.11 (2.57–10.3)), lymphopaenia (OR 4.41 (2.51–11.5)) and low C3 (OR 1.91 (1.03–4.37)) in multivariate analysis. 65 representative patients with neutropaenia were analysed. Neutropaenia was moderate to severe in 38%, chronic in 31%, and both severe and chronic in 23% of cases. Moderate to severe and chronic neutropaenia were both associated with lymphopaenia and thrombopaenia. Chronic neutropaenia was also associated anti-Ro/SSA antibodies and moderate to severe neutropaenia with oral ulcers.ConclusionThis study is to date the largest cohort to describe neutropaenia in SLE. Neutropaenia displays a strong association with other cytopaenias, suggesting a common mechanism. Chronic neutropaenia is associated with anti-Ro/SSA antibodies with or without identified Sjögren’s disease.

ObjectivesTo investigate whether bortezomib, a proteasome inhibitor approved for treatment of multiple myeloma, induces clinically relevant plasma cell (PC) depletion in patients with active, refractory systemic lupus erythematosus (SLE).MethodsTwelve patients received a median of two (range 1–4) 21-day cycles of intravenous bortezomib (1.3 mg/m2) with the coadministration of dexamethasone (20 mg) for active SLE. Disease activity was assessed using the SLEDAI-2K score. Serum concentrations of anti–double-stranded DNA (anti-dsDNA) and vaccine-induced protective antibodies were monitored. Flow cytometry was performed to analyse peripheral blood B-cells, PCs and Siglec-1 expression on monocytes as surrogate marker for type-I interferon (IFN) activity.ResultsUpon proteasome inhibition, disease activity significantly declined and remained stable for 6 months on maintenance therapies. Nineteen treatment-emergent adverse events occurred and, although mostly mild to moderate, resulted in treatment discontinuation in seven patients. Serum antibody levels significantly declined, with greater reductions in anti-dsDNA (∼60%) than vaccine-induced protective antibody titres (∼30%). Bortezomib significantly reduced the numbers of peripheral blood and bone marrow PCs (∼50%), but their numbers increased between cycles. Siglec-1 expression on monocytes significantly declined.ConclusionsThese findings identify proteasome inhibitors as a putative therapeutic option for patients with refractory SLE by targeting PCs and type-I IFN activity, but our results must be confirmed in controlled trials.