Association Between Serum Alarmin Levels and Disease-specific Indices in Patients With Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis

Abstract

Background/Aim: We evaluated the relationship between serum alarmin levels and disease-specific indices in patients with anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitis (AAV). Patients and Methods: Sera and data from 79 patients were utilized. For AAV-specific indices, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index (VDI) were collected and serum levels of four alarmins (hepatoma-derived growth factor, high mobility group box protein 1, S100A9, and S100A12) were measured using enzyme-linked immunosorbent assay. Associations between alarmin levels, AAV-specific indices, and inflammatory laboratory markers were assessed. Results: S100A9 levels were significantly correlated with Creactive protein levels (r=0.316, p=0.005) and S100A12 levels correlated with VDI (r=0.232, p=0.040), which was consistent in a subgroup of patients with myeloperoxidase (perinuclear)-ANCA positivity. No other associations were found between alarmin levels and BVAS, FFS, and VDI. Conclusion: The serum S100A12 level was associated with organ damage in AAV, especially in myeloperoxidase (perinuclear)-ANCApositive patients.Alarmins, often used interchangeably with the term 'damageassociated molecular patterns' are defined as an endogenous group of molecules that are released due to cellular injury or damage (1). First described as damage-associated molecular patterns in 2004 by Seong et al., alarmins are expressed constitutively in various cells and are thought to play a critical role in cellular regeneration and remodeling (2). Alarmins may also act as potent mediators of inflammation by promoting chemotaxis and inducing the expression of proteins implicated in immune activation when they are secreted extracellularly (3). Mechanistically, secreted alarmins bind to pattern recognition receptors, i.e. Toll-like receptors and receptors for advanced glycation end-products, to elicit their physiological effects. Dysregulation of this signaling can trigger aberrant immune responses (4, 5). Previous studies have indicated that among the alarmins, hepatoma-derived growth factor (HDGF), high mobility group box protein 1 (HMGB1), and S100 proteins can play important roles in autoimmunity (6-8).Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune condition that belongs to a group of primary systemic vasculitides. A typical pathological feature of AAV is the presence of necrotizing inflammation in small-sized vessels, such as intraparenchymal arteries, arterioles, capillaries, and venules, and various organ involvement may be present in AAV (9). AAV comprises three distinct diseases: Microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis. These diseases can be differentiated according to their clinicopathological and laboratory findings of ANCA serology. As mentioned above, based on the crucial role of alarmins in the immune system, several previous studies have demonstrated that the...