Our initial results, obtained in two independent sets of LN kidney biopsies, conﬁrmed our hypothesis that intrarenal activation of adaptive immune effectors is associated with tubular damage and decreased renal function in LN (1).
Single cell gene expression proﬁling of (CD3-CD14-CD16-CD27+ CD38high) plasma cells (PC) was performed using kidney biopsies and blood from patients with a ﬂare of class III/IV LN treated or not with mycophenolate mofetil (MMF). We obtained single kidney plasma cells that we compared with long-lived plasma cells from the bone marrow of heathy donors. In untreated patients, most PC were plasmablasts expressing multiple genes involved in cell division. By contrast, PC from the kidney of MMF-treated patients were over-expressing multiple plasmacell speciﬁc genes while not harboring a proliferative proﬁle.
Similarly, single cell RNASeq and clonal expansion of CD8 T cells from kidney, urine and blood from patients with a severe flare of class III/IV LN showed the presence of clonally expanded CD8 T cells with an activated phenotype. One of these clones displayed cytotoxic properties against cultured renal tubular cells that were abrogated after targeted deletion of the T Cell Receptor.