Anti-ADAMTS13 Autoantibodies: From Pathophysiology to Prognostic Impact-A Review for Clinicians

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease in which platelet-rich microthrombi cause end-organ ischemia and damage. TTP is caused by markedly reduced ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. ADAMTS13 autoantibodies (autoAbs) are the major cause of immune TTP (iTTP), determining ADAMTS13 deficiency. The pathophysiology of such autoAbs as well as their prognostic role are continuous objects of scientific studies in iTTP fields. This review aims to provide clinicians with the basic information and updates on autoAbs' structure and function, how they are typically detected in the laboratory and their prognostic implications. This information could be useful in clinical practice and contribute to future research implementations on this specific topic.

Keywords: ADAMTS13 autoantibodies; ADAMTS13 inhibitors; Moskowitz syndrome; thrombotic thrombocytopenic purpura.

Figure 1

ADAMTS13 enzyme structure and major autoAbs binding sites. ADAMTS13 is a multidomain metalloprotease consisting of a signal peptide domain (S), a short propeptide domain (P), a metalloprotease (M) domain, a disintegrin-like (Dis) domain, a first thrombospondin type 1 (TSP1) repeat, a cysteine-rich (Cys) domain and a Spacer domain. It has seven additional thrombospondin type 1 repeats (TSP2-8) and two CUB domains (CUB1-2) [13]. Major epitope binding sites are the Cys-Spacer domain, the CUBs domain (see main text), the Dys domain and the TSP fragments and domains.