Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS 13 provide a common antigenic core required for binding of antibodies in patients with acquired TTP

作者：Luken Brenda M; Turenhout Ellen A M; Kaijen Paul H P; Greuter Mascha J; Pos Wouter; van Mourik Jan A; Fijnheer Rob; Voorberg Jan^*

来源：Thrombosis and Haemostasis, 2006, 96(3): 295-301.

DOI：10.1160/TH06-03-0135

• ADAMS/ADAMTS 13
• autoantibodies
• thrombotic thrombocytopenic purpura
• TTP
• HUS

Antibodies directed against ADAMTS13 have been detected in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). We have previously localized a major antigenic determinant within the spacer domain of ADAMTS13. To identify the amino acid residues of the spacer domain that are involved in binding of anti-ADAMTS13 antibodies, we constructed a series of fifteen hybrids (designated A-O) in which 5-10 amino acids of the spacer domain were exchanged for the corresponding region of ADAMTS1. Plasma from six patients with antibodies directed against the spacer domain was analyzed for reactivity with the ADAMTS13/ADAMTS1 chimeras. Exchange of amino acid residues 572-579 (hybrid C) and 657-666 (hybrid M) completely abolished the binding of antibodies from all six patients analyzed. Regions 580-587 (D), 602-620 (G,H), 629-638 (J), and 667-767 (N) contributed to binding of antibodies from patients 2,4, and 5 (epitope present within regions (C) under bar DGHJ (M) under barN). Antibodies derived from patient 1 required region 602-620 (G,H) for binding ((C) under bar CGH (M) under bar -epitope). For antibodies of patient 3, residues 564-571 (B), 580-587 (D), and 629-638 0) were required (B (C) under bar DJ (M) under bar -epitope), whereas replacement of residues 602-610 (G) and 629-638 0) greatly diminished binding of antibodies from patient 6 (C) under bar GJ (M) under bar -epitope). Despite the presumably polyclonal origin of the antibodies present in plasma of patients, our results suggest that residues 572-579 (C) and 657-666 (M) comprise a common antigenic core region that is crucial for binding of anti-ADAMTS13 antibodies. Other regions that spatially surround this antigenic core further modulate binding of antibodies to the spacer domain.

• 出版日期2006-9