D2.427 - Inhibition of the IL-17 pathway in the treatment of systemic vasculitis: molecular biology and case review

Interleukin (IL)-17A is a proinflammatory cytokine implicated in the pathogenesis of many autoimmune diseases. IL-17A acts on all cell types of the three layers of the vascular wall to promote inflammation, coagulation, and thrombosis. IL-17 induces the production of many other cytokines (such as IL-6, G-CSF, GM-CSF, IL-1β, TGF-β, TNF-α), chemokines (including IL-8, GRO-α, and MCP-1), and prostaglandins (e.g., PGE2) from many cell types (fibroblasts, endothelial cells, epithelial cells, keratinocytes, and macrophages). IL-17A, and even more so when combined with tumor necrosis factor (TNF)-α, affects all cell types of the vascular wall;Recruitment of immunocompetent cells is also facilitated by increased expression of adhesion molecules. IL-17A induces thrombosis, coagulation, and apoptosis. All biologics that directly target the IL-17 pathway are available, but secukinumab was the only one tested in vasculitis.

We studied two patients. One patient was male, 13 year-old with swollen, eroded, purpuric plaques with a central hemorrhagic crust over the right scapula. A left lateral forehead needle biopsy revealed necrotizing angiitis with a neutrophil-dominant inflammatory infiltrate in small and medium-sized dermal vessels, extravasation of erythrocytes, and extravascular granulomas with scattered giant cells. The combination of pathology and clinical findings supported the diagnosis of GPA. The second patient was female, 16 year-old and during physical examination, the patient had fever, tachycardia, and hypertension. An ulcerated plaque with hyperpigmentation was located above the umbilicus; needle biopsies from the left elbow and shoulder showed findings similar to those of the first patient.

The use of secukinumab in patients with ANCA-positive granulomatosis has shown positive results. During the treatment period, patients had a significant decrease in erythrocyte sedimentation rate after 5 and 10 weeks of treatment, indicating that it has a positive effect on reducing inflammation.

IL-17 A is a proinflammatory cytokine involved in many autoimmune processes, including the pathogenesis of systemic vasculitis; According to the Chapel Hill consensus, four main groups of vasculitis are distinguished: large, medium, small and variable vessel vasculitis; ANCA-positive granulomatosis with polyangiitis occurs mainly in adolescents, its exact prevalence in Georgia is unknown, although it has been observed in the pediatric contingent; Patients can be assessed using ACR/EULAR criteria and the sum of the scores allows us to assess the severity of the disease; Treatment with the IL-17 inhibitor secukinumab gives positive results and the erythrocyte sedimentation rate of patients decreases; The use of this medication contributes to a sharp weakening not only of vasculitis, but also of the progression of arthritis and has a positive result.