Increased Frequency of T Peripheral Helper Cells and Plasmablasts Correlates with Disease Activity in Childhood-Onset Systemic Lupus Erythematosus with Nephritis

To further understand the immunopathogenesis of childhood-onset SLE (cSLE), particularly LN, with the ultimate goal of better patient-specific therapy, we characterized the immunologic status of treatment-naïve cSLE patients (with and without LN) at disease onset and over time (longitudinal) compared to age and sex-matched healthy controls. We integrated clinical, mass cytometry (CyTOF), and gene expression data (DxTerity®). We applied traditional a priori knowledge-guided and unbiased computational analyses to capture high-dimensional phenotypic (i.e., cell identity) and functional (i.e., cytokine, activation, interferon-response) parameters, relevant to ?patient-level? and ?organ-level? phenotypes, to identify biologically meaningful signals that may escape conventional approaches.
Conclusion:
We performed peripheral blood immune profiling via mass cytometry and gene expression analysis in 24 newly diagnosed untreated cSLE patients, with longitudinal follow up over three years. We discovered LN-specific correlates of disease activity including CD8+ T cell activation, increased frequency of T peripheral helper cells and plasmablasts, and B cell cytokine production. These findings support further investigation of T and B cell functions underlying renal pathogenesis.