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ADAMTS13 phenotype in plasma from normal individuals and patients with thrombotic thrombocytopenic purpura

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Abstract

The activity of ADAMTS13, the von Willebrand factor cleaving protease, is deficient in patients with thrombotic thrombocytopenic purpura (TTP). In the present study, the phenotype of ADAMTS13 in TTP and in normal plasma was demonstrated by immunoblotting. Normal plasma (n = 20) revealed a single band at 190 kD under reducing conditions using a polyclonal antibody, and a single band at 150 kD under non-reducing conditions using a monoclonal antibody. ADAMTS13 was not detected in the plasma from patients with congenital TTP (n = 5) by either antibody, whereas patients with acquired TTP (n = 2) presented the normal phenotype. Following immunoadsorption of immunoglobulins, the ADAMTS13 band was removed from the plasma of the patients with acquired TTP, but not from that of normal individuals. This indicates that ADAMTS13 is complexed with immunoglobulin in these patients. The lack of ADAMTS13 expression in the plasma from patients with hereditary TTP may indicate defective synthesis, impaired cellular secretion, or enhanced degradation in the circulation. This study differentiated between normal and TTP plasma, as well as between congenital and acquired TTP. This method may, therefore, be used as a complement in the diagnosis of TTP.

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Fig. 1a–g

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Abbreviations

ADAMTS13:

a disintegrin-like and metalloprotease with thrombospondin-type-1 motifs, 13

ELISA:

enzyme-linked immunosorbent assay

HUS:

hemolytic uremic syndrome

TMA:

thrombotic microangiopathy

TTP:

thrombotic thrombocytopenic purpura

ULVWF:

ultra-large von Willebrand factor

VWF:

von Willebrand factor

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Acknowledgments

The authors thank Professor M. Furlan, Central Hematology Laboratory, Inselspital, University of Bern, Switzerland, for initially performing the ADAMTS13 protease activity assays on patients 1, 2, and 3. We also thank Drs. Y. Fujimura and H. Hiura for providing us with their monoclonal (A10) mouse anti-ADAMTS13 antibody.

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Authors and Affiliations

  1. Department of Pediatrics, Clinical Sciences Lund, Lund University, 221 84, Lund, Sweden

    Minola Manea, AnnCharlotte Kristoffersson, Lars Holmberg & Diana Karpman

  2. Division of Hematology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA

    Han-Mou Tsai & Wenhua Zhou

  3. Department of Hematology, Lund University Hospital, Lund, Sweden

    Ingemar Winqvist

  4. Department of Pediatrics, Länssjukhuset Ryhov, Jönköping, Sweden

    Göran Oldaeus

  5. Department of Hematology, Kärnsjukhuset, Skövde, Sweden

    Rolf Billström

  6. Department of Medicine, Malmö University Hospital, Malmö, Sweden

    Peter Björk

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  1. Minola Manea
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  2. AnnCharlotte Kristoffersson
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  3. Han-Mou Tsai
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  4. Wenhua Zhou
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  9. Lars Holmberg
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  10. Diana Karpman
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Corresponding author

Correspondence to Diana Karpman.

Additional information

Grants: This study was supported by grants from the Swedish Research Council (06X-14008 to DK and 04997 to LH), Swedish Renal Foundation, Anna-Lisa and Sven-Eric Lundgren Foundation for Medical Research, Greta and Johan Kock Foundation, Crafoord Foundation, Inga and John Hains Foundation, Alfred Österlund Foundation, Crown Princess Lovisa’s Society for Child Care, Thelma Zoegas Foundation, Sven Jerring Foundation, the Swedish Society of Nephrology, Åke Wiberg Foundation, the Blood and Defence Network at Lund University, Magnus Bergvalls Foundation, and Maggie Stephens Foundation (all to DK); the Ellen Bachrach Foundation (to ACK); National Heart, Lung and Blood Institute of the NIH (R01 HL62136 and R01 HL72876 to H-MT); Slättens Ideella Barnhjälp (to LH).

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Manea, M., Kristoffersson, A., Tsai, HM. et al. ADAMTS13 phenotype in plasma from normal individuals and patients with thrombotic thrombocytopenic purpura. Eur J Pediatr 166, 249–257 (2007). https://doi.org/10.1007/s00431-006-0354-2

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