Detection of Circulating ADAMTS13 Immune Complexes by Antibody Class-Specific ELISA

Abstract 4361

A severe functional deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13 results in the accumulation of uncleaved, highly adhesive VWF multimers in plasma leading to increased platelet aggregation and thrombus formation in the microcirculation. Anti-ADAMTS13 autoantibodies that either neutralize ADAMT13’s activity or enhance protein clearance are the major cause of severe ADAMTS13 deficiency in acquired thrombotic thrombocytopenic purpura (TTP). Circulating anti-ADAMTS13 immune complexes that may play a role in disease pathogenesis have been described in plasma of TTP patients. We have developed a new ELISA assay to specifically determine the levels of ADAMTS13-specific circulating immune complexes (CIC) in which the antigen portion is immobilized by a polyclonal anti-ADAMTS13 IgG and the immunoglobulin component detected by a class-specific antibody. An inverse correlation between levels of circulating anti-ADAMTS13 autoantibodies and ADAMTS13-specific CIC has been observed in plasma of acquired TTP patients. The correlation between free anti-ADAMTS13 titer and the level of CIC and insight into the immunoglobulin (sub) classes involved may provide valuable prognostic information about disease severity and progression, and aid patient treatment monitoring.