Therapeutic efficacy of IL-17 blockade identifies lichen planus as a Th17-driven skin disorder

Department of Dermatology and Allergology, Philipps-University, Marburg, Germany

LP is a common chronic inflammatory disorder of skin and mucous membranes whose immune pathogenesis has been linked to T cell-mediated cytotoxicity against epidermal keratinocytes. Recently, we identified autoreactive Th1 and Th17 responses in a cohort of LP patients which recognized bullous pemphigoid antigen 180 (BP180) and desmoglein 3 (Dsg3), well-known autoantigens of the skin. Of note, BP180-reactive peripheral Th17 cells were significantly increased in LP patients with mucosal and skin lesions. We here studied the clinical efficacy of secukinumab, a monoclonal antibody against IL-17a, in three patients with acute and chronic recalcitrant muco-cutaneous LP. Secukinumab was applied for 13 weeks and the patients were monitored clinically by the Autoimmune Bullous Skin Intensity Score (ABSIS) and immunologically (analysis of lesional cutaneous T cell subsets and peripheral BP180- and Dsg3-specific T cells by immunohistochemistry and Elispot analysis before, during and after secukinumab treatment. After 13 weeks of therapy, all the three LP patients (P1-3) showed a remarkable clinical resolution of the skin and mucosal lesions with a clear decrease of the ABSIS scores (ABSIS I: P1: 5 to 0, P2: 7 to 2, P3: 3.5 to 1; ABSIS II: P1: 45 to 0, P2: 21 to 0, P3: 11.5 to 0). This was accompanied by a strong reduction of the inflammatory skin infiltrate and a relative decrease of lesional T cells (percentage of CD3+ cells of all infiltrating cells before therapy: 52.8%+/-15, after therapy: 39.1%+/-5.5). Although BP180- and Dsg3-specific Th1 and Th17 cells were detectable throughout the observation period, we could not detect a decrease of autoreactive Th17 cells upon treatment with secukinumab. These findings show for the first time that mucosal and cutaneous LP rapidly responds to therapeutic inhibition of IL-17a and strongly support the concept that Th17 cells are critically involved in the immune pathogenesis of LP.