Soluble immune checkpoint molecules in patients with antineutrophil cytoplasmic antibody-associated vasculitis

Abstract

Immune checkpoint molecules balance immune effector responses with regulatory reactions. We speculated that soluble immune checkpoint molecules are involved in dysregulation of the immune response and autoimmunity. We evaluated the association between soluble immune checkpoint molecules and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A total of 56 patients with AAV from a prospective observational cohort and 40 healthy controls (HCs) were analyzed. Soluble PD-1, PD-L1, PD-L2, CTLA-4, CD28, CD80, CD86, ICOS, TIM-3, BTLA, CD40, LAG-3, TLR-2, and CD27 were measured in stored sera using the Milliplex MAP assay. Paired analyses were performed before and after the treatment. AAV-specific indices, including Birmingham vasculitis activity score, five factor score , vasculitis damage index, and blood samples, were collected. Patients with AAV had higher levels of sPD-L1, sCD28, sCD80, sCD86, sICOS, sTIM-3, sLAG-3, sTLR-2, and sCD27 and lower level of sCTLA-4 than HCs (p < 0.05). Patients with AAV had higher serum sCD28, sCD80, sTIM-3, and sCD27 levels than HCs at baseline and decreased after treatment. Furthermore, the serum levels of sCD28 and sTIM-3 were significantly correlated with disease activity. This study demonstrated altered concentrations of serum soluble immune checkpoint molecules in patients with AAV. In particular, sCD28 and sTIM-3 may act as surrogate markers of AAV disease activity.