HLA-DRhigh/CD27high plasmablasts indicate active disease in patients with systemic lupus erythematosus

Objectives: Monitoring of peripheral B-cell subsets in patients with systemic lupus erythematosus (SLE) revealed an activity-related expansion of CD27(++)CD20(-)CD19(dim) Ig-secreting cells. A similar subset has also been identified 6-8 days after tetanus/diphtheria vaccination in normal individuals and in patients with infectious disease. Methods: This subset was analysed further focussing on the HLA-DR surface expression in a cohort of 25 patients with SLE. Results: This study revealed that 86% (range 59-97%) of CD27(++)CD20(-)CD19(dim) cells express high levels of HLA-DR, are also expanded in the bone marrow, and represent plasmablasts enriched with anti-dsDNA secreting cells. The remaining CD27(++)CD20(-)CD19(dim) cells were HLA-DRlow and represent mature plasma cells. Importantly, HLA-DRhigh plasmablasts showed a closer correlation with lupus activity and anti-dsDNA levels than the previously identified CD27(++)CD20(-)CD19(dim) cells. Conclusion: HLA-DR(high)CD27(++)CD20(-)CD19(dim) plasmablasts represent a more precise indicator of lupus activity and suggest that there is an overproduction or lack of negative selection of these cells in SLE.