Article
Cellular biomarkers in SLE to monitor immune cell- and cell signalling-dynamics
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Published: | October 8, 2019 |
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Background: Cellular biomarkers are coming in focus to monitor disease activity, guide personalized treatment decisions and replace kidney biopsies in systemic lupus erythematosus (SLE). Hitherto, humoral biomarkers, such as autoantibodies, complement consumptions or creatinine are still the gold standard in lupus diagnostics, although they are only of limited value for the challenges facing precision medicine in SLE.
Methods: Here we will sum up latest results of our explorative biomarker discovery studies using highly multiplexed mass cytometry to analyse peripheral blood and urine samples for disease-specific changes in immune cell dynamics and for signalling abnormalities at the single cell level.
Results: Deep phenotyping of urinary cells revealed neutrophilic granulocytes, macrophages and different T cell subsets as predominating cell types while B cells, NK and eosinophils were found only rarely observed in lupus nephritis. The presence of activated urinary T cells and monocytes could be used for differential diagnosis of proliferative LN forms and other renal pathologies. Most interestingly, the frequency of effector memory CD4 cells in the urine sediment was predictive for a worse response to an induction therapy by immunosuppressive drugs and a diminished chance to achieve complete remission. Finally, we want to show first results of using mass cytometry for profiling of cell signaling pathways in active and JAK inhibitor-treated SLE patients. A successful inhibition of JAK signaling by Baricitinib, the clinical improvement of the patients was paralleled by a decrease of monocytic CD169 expression (a type I interferon response marker) and decreased detection levels of pSTAT1 phosphorylation in CD4+ and CD8+ T cells and monocytes.
Conclusion: Altogether, cellular biomarkers identified revealed as promising new options in lupus diagnostics that will open new avenues for precision medicine in autoimmune disease.