Relation between ADAMTS13 activity and ADAMTS13 antigen levels in healthy donors and patients with thrombotic microangiopathies (TMA).
We have established a new, enzyme-linked immunosorbent assay (ELISA) for the detection of ADAMTS13 antigen using purified polyclonal rabbit anti-human ADAMTS13 IgG. Normal plasma ADAMTS13 antigen levels span a concentration of 740-1420 ng/ml (median 1080 ng/ml) resulting in an ADAMTS13 activity to antigen ratio of 0.48 to 1.68 U/mug. In a cohort of HUS patients, ADAMTS13 antigen was in the normal range, whereas in hereditary TTP patients antigen levels were low to undetectable, in concordance with severe deficient ADAMTS13 activity. Plasma of acquired TTP patients was found to contain free as well as autoantibody-bound ADAMTS13. We also present evidence for circulating anti-ADAMTS13 antibody/ADAMTS13 antigen immune complexes not only in acutely ill or actively treated patients but also in patients who have already achieved clinical remission. This new developed ADAMTS13 antigen ELISA assay allows rapid determination of ADAMTS13 antigen levels in human plasma but is of limited predictive value for the diagnosis or treatment of acquired TTP due to the detection of ADAMTS13 in antibody complexes.
Department of Discovery Research, Baxter Bioscience, Wagramer Strasse 17-19, A-1220 Vienna, Austria.
Manfred
M
Rieger
Silvia
S
Ferrari
Johanna A
JA
Kremer Hovinga
Christian
C
Konetschny
Andrea
A
Herzog
Letizia
L
Koller
Alfred
A
Weber
Giuseppe
G
Remuzzi
Michael
M
Dockal
Barbara
B
Plaimauer
Friedrich
F
Scheiflinger
D051722:ADAM Proteins / Q000097:blood* / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood; D000941:Antigens / Q000097:blood; D001782:Blood Donors; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology*; D011817:Rabbits
D000936:Antigen-Antibody Complex; D000941:Antigens; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human