Antibodies against the CUB1-2 domains of ADAMTS13 in a patient with benign monoclonal gammopathy: no causal relationship

Abstract

We present a patient with a history of benign monoclonal gammopathy, who developed thrombotic thrombocytopenic purpura (TTP), initially presenting as bilateral serous retinal detachment. Plasma of the patient contained high titers of anti-ADAMTS13 antibodies that were directed towards the disintegrin/TSR1/cysteine-rich/spacer and CUB1-2 domains. ADAMTS13 activity was undetectable. Total IgG purified from plasma of the patient partially inhibited ADAMTS13 activity. In contrast, the isolated M-protein did neither bind to, nor inhibit activity of ADAMTS13. We conclude that in this patient the monoclonal gammopathy and TTP co-existed as distinct pathological entities.

Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare disorder associated with the presence of unusually large von Willebrand factor (VWF) multimers in plasma, which induce platelet aggregation and consumption, tissue ischaemia, and microangiopathic haemolytic anaemia.1 Unusually large VWF multimers arise as a consequence of severely reduced activity of the VWF-cleaving protease ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains).1 In most patients with acquired TTP, antibodies directed to the cysteine-rich/spacer domains of ADAMTS13 are present.2–5

In the current study, we describe a patient with a history of benign monoclonal gammopathy who developed TTP, and initially presented with bilateral serous retinal detachment. We hypothesized that in this patient the monoclonal immunoglobulin (M-protein) was directed against ADAMTS13, and we conducted a series of in vitro experiments to test this hypothesis.