Postvaricella purpura fulminans caused by acquired protein S deficiency resulting from antiprotein S antibodies: Search for the epitopes

Postvaricella purpura fulminans is a rare disease in children that is probably caused by an acquired protein S deficiency resulting from antiprotein S antibodies. The epitope of these antibodies is unknown. A 5-year-old girl is described with postvaricella purpura fulminans and an acquired protein S deficiency. In this patient and in her 3-year-old sister with uncomplicated varicella, the concentrations of antiprotein S antibodies were measured and followed with enzyme-linked immunosorbent assay techniques. The epitope of the antiprotein S antibodies was studied using miniprotein S, a recombinant variant of protein S that consists of the first 242 amino acids of protein S, lacking the sex hormone binding globulin-like domain. In the patient's plasma, concentrations of free protein S antigen and total protein S antigen reached normal levels in 4 months and 5 weeks, respectively. The concentrations of the antiprotein S antibodies decreased to 25% of the initial level in the course of 5 months. In the sister, antiprotein S antibodies were present as well, but the concentrations were lower than those in the patient. Most of the antiprotein S antibodies were directed against the first 242 amino acids of protein S. After varicella, a heterozygous autoantibody response may develop that may result in severe acquired protein S deficiency leading to purpura fulminans. Epitopes of these antiprotein S antibodies are situated on both the first 242 amino acids of protein S and the sex hormone binding globulin-like domain