Increased Myeloid Dendritic Cells and TNF-α Expression Predicts Poor Response to Hydroxychloroquine in Cutaneous Lupus Erythematosus

Although antimalarials are the primary treatment for cutaneous lupus erythematosus, not all patients are equally responsive. We investigated whether different inflammatory cell population and cytokine profiles in lesional cutaneous lupus erythematosus skin could affect antimalarial responsiveness, and whether hydroxychloroquine (HCQ) and quinacrine (QC) differentially suppress inflammatory cytokines. Cutaneous lupus erythematosus patients were grouped according to their response to antimalarials (HCQ vs. HCQthornQC). On immunohistochemistry, only the myeloid dendritic cell population was significantly increased in the HCQthornQC group compared to HCQ group. While the IFN scores calculated for the selected type I IFNeregulated genes (LYE6, OAS1, OASL, ISG15, and MX1) were significantly higher in the HCQ group than the HCQthornQC group, the TNF-alpha level was higher in the HCQthornQC group. QC was more effective than HCQ at inhibiting the toll receptor-mediated production of TNF-alpha and IL-6 in the peripheral blood mononuclear cells isolated from cutaneous lupus erythematosus patients, whereas QC and HCQ inhibited IFN-alpha equally. QC also suppressed phosphoeNF-kB p65 more profoundly than HCQ. In conclusion, increased myeloid dendritic cell population with higher TNF-alpha expression might contribute to HCQ refractoriness and a better response to QC. Differential suppressive effects of HCQ and QC could also affect antimalarial responses in cutaneous lupus erythematosus patients.