Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura

Christoph Klaus, Barbara Plaimauer, Jan Dirk Studt, Friedrich Dorner, Bernhard Lämmle, Pier Mannuccio Mannucci, Friedrich Scheiflinger

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 can lead to thrombotic thrombocytopenic purpura (TTP), a disease associated with the widespread formation of platelet-rich thrombi in many organs. Autoantibodies that inactivate ADAMTS13 are the most frequent cause of acquired TTP. Little is known about epitope specificity and reactivity of anti-ADAMTS13 antibodies. In this study, a series of ADAMTS13 domains were expressed in Escherichia coli, and the reactivity of purified recombinant fragments with anti-ADAMTS13 autoantibodies from 25 patients with severe ADAMTS13 deficiency was evaluated in vitro. All TTP plasmas contained antibodies directed against the cysteine-rich spacer (cys-rich/spacer) domain of ADAMTS13. In the plasma of 3 patients, antibodies were detected that reacted exclusively with the cys-rich/spacer domain, underscoring the importance of this region for functional activity of ADAMTS13. In 64% of the plasmas, antibodies reacted with the 2 CUB domains, and in 56% they reacted with the isolated first thrombospondin type 1 (TSP-1) repeat and with the compound fragment consisting of the catalytic, the disintegrin-like, and the TSP1-1 domain. Less frequently, in 28% of the plasmas, antibodies reacted with the TSP1 repeats 2 to 8. Unexpectedly, antibodies reacted with the propeptide region in 20% of the plasmas. In conclusion, this study shows that even though anti-ADAMTS13 autoantibodies react with multiple domains of the protease, the cys-rich/spacer domain is consistently involved in antibody reactivity.

Original languageEnglish
Pages (from-to)4514-4519
Number of pages6
JournalBlood
Volume103
Issue number12
DOIs
Publication statusPublished - Jun 15 2004

Fingerprint

Epitope Mapping
Autoantibodies
Epitopes
Antibodies
Plasmas
Thrombotic Thrombocytopenic Purpura
Cysteine
Thrombospondin 1
Disintegrins
Cysteine Proteases
von Willebrand Factor
Platelets
Acquired Thrombotic thrombocytopenic purpura
Anti-Idiotypic Antibodies
Thrombosis
Escherichia coli
Blood Platelets
Peptide Hydrolases

ASJC Scopus subject areas

  • Hematology

Cite this

Klaus, C., Plaimauer, B., Studt, J. D., Dorner, F., Lämmle, B., Mannucci, P. M., & Scheiflinger, F. (2004). Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. Blood, 103(12), 4514-4519. https://doi.org/10.1182/blood-2003-12-4165

Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. / Klaus, Christoph; Plaimauer, Barbara; Studt, Jan Dirk; Dorner, Friedrich; Lämmle, Bernhard; Mannucci, Pier Mannuccio; Scheiflinger, Friedrich.

In: Blood, Vol. 103, No. 12, 15.06.2004, p. 4514-4519.

Research output: Contribution to journalArticle

Klaus, C, Plaimauer, B, Studt, JD, Dorner, F, Lämmle, B, Mannucci, PM & Scheiflinger, F 2004, 'Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura', Blood, vol. 103, no. 12, pp. 4514-4519. https://doi.org/10.1182/blood-2003-12-4165
Klaus, Christoph ; Plaimauer, Barbara ; Studt, Jan Dirk ; Dorner, Friedrich ; Lämmle, Bernhard ; Mannucci, Pier Mannuccio ; Scheiflinger, Friedrich. / Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. In: Blood. 2004 ; Vol. 103, No. 12. pp. 4514-4519.
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