Serp-1 Treatment for Diffuse Alveolar Hemorrhage in Systemic Lupus Erythematosus; Analysis of Efficacy and Mechanism of Action

Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in widespread inflammation of various organ tissues including the lung, heart, kidneys, brain, joints, vasculature, and more. Systemic Lupus Erythematosus (SLE) has at present no cure and therefore, treatments focus on improving quality of life by targeting flare-ups of inflammation (6). Diffuse Alveolar Hemorrhage (DAH) is a rare complication of SLE affecting 1-5% of people diagnosed with SLE. DAH is characterized by bleeding into the lung alveolar spaces and is associated with inflammation, potentially caused by infections and injuries. While the prevalence of DAH is low, the mortality rate is high at 50-80% (5). DAH has no proven effective treatment and many treatments used have severe side effects. Serp-1 is a Myxomavirus derived immune modulating serine protease inhibitor, a serpin, with proven efficacy in a wide range of inflammation-associated disorders (1). Due to the efficacy of Serp-1 in reducing arterial inflammation and lung consolidation in mouse herpes virus infections, Serp-1 treatment in a mouse model of pristane-induced DAH was investigated. Multiple groups were tested including mouse models that were not given pristane as well as mice with pristane-induced DAH treated with saline control, wild-type unmodified Serp-1, and a polyethylene glycol-modified variant of Serp-1 termed PEGSerp-1.