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SAT0178 IGA+ plasmablasts contribute to the expansion of peripheral plasmablasts in SLE
  1. S. Schmidt1,2,
  2. B.F. Hoyer1,2,
  3. H.E. Mei1,2,
  4. T. Dörner1,2
  1. 1German Rheumatism Research Center Berlin (DRFZ)
  2. 2CC12, Clinical Immunology and Rheumatology, Charité University Medicine Berlin, Berlin, Germany


Background Active systemic lupus erythematosus (SLE) is associated with increased levels of peripheral blood antibody-secreting plasmablasts which correlate with autoantibody production and disease activity. Plasmablasts which circulate in healthy individuals at very low levels in steady-state express a mucosal phenotype and secrete IgA, but are conditionally expanded by additional IgG-secreting plasmablasts during systemic immune responses. The dynamics of plasmablasts generated in mucosal IgA vs. systemic IgG responses underlying the expanded plasmablast subset in SLE patients and its implication in SLE immunopathogenesis remain unexplored.

Objectives To analyse the blood of SLE patients for the presence and characteristics of IgA+ plasmablasts and to evaluate their potential relation to SLE disease activity.

Methods Peripheral blood plasmablasts from 30 SLE patients and 20 healthy controls (HD) were enumerated and analysed by multi-parametric flow cytometry using antibodies directed against CD19, CD27, CD20, and analysed for surface co-expression of IgA, CCR10 and beta7 Integrin. Disease activity was assessed by SLEDAI scores.

Results IgA+ plasmablasts were detected in the blood of all controls and at significantly higher numbers in SLE patients (HD, IgA+ 1,2 cells/μl; SLE, IgA+ 3,2 cells/μl; p=0.0017). Patients with high disease activity (SLEDAI ≥6) showed significantly higher numbers of circulating IgA+ plasmablasts when compared with less active patients at SLEDAI<6 (p=0.0442). In both patients and controls, the majority of plasmablasts expressed at least one of the mucosal markers, i.e. IgA, beta7 Integrin or CCR10, suggesting their generation in mucosal immune responses.

In SLE patients, expression of CCR10 and beta7 integrin was associated with IgA expression. However, we found that a unique IgA+/CCR10-/beta7- plasmablast subset disproportionately contributed to the expansion of IgA+ plasmablasts in the blood of SLE patients (HD, 25%; SLE, 38%). In contrast, IgA+ plasmablasts expressing CCR10 but not beta7 Integrin were significantly reduced in SLE patients compared to healthy controls (HD, 48%; SLE, 29%; p=0,0182).

Conclusions Our data demonstrate that IgA+ plasmablasts contribute to the expanded plasmablast subset in SLE patients related to disease activity. The data implicate enhanced activation and differentiation of mucosal B cells, although the expansion of a distinct IgA+ plasmablast subset lacking mucosal homing receptors beta7 Integrin and CCR10 indicates abnormalities of mucosal B cell activation in these patients.

Disclosure of Interest None Declared

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