ADAMTS13-binding IgG are present in patients with thrombotic thrombocytopenic purpura

Summary

Functional assays are commonly used to measure the antibodies of ADAMTS13 found in patients of thrombotic thrombocytopenic purpura (TTP). In this study we used an enzyme-linked immunoassay to analyze the ADAMTS13-binding IgG levels in six groups of individuals: normal, random hospitalized patients, acute TTP,TTP after receiving plasma therapy,TTP in remission, and other types of thrombotic microangiopathy (TMA).The results showed that ADAMTS13-binding IgG levels were elevated in 100% of the acute TTP group, 75% of the TTP group after receiving plasma therapy, and 40% of the remission group. Overall, the ADAMTS13-binding IgG levels correlated with the inhibitory activity levels againstADAMTS13 (r = -0.69,P<0.0001).The assay also detected elevated IgG binding levels in 5% - 15% of the normal, random, and other TMA control groups.Addition of purified ADAMTS13 protein to the plasma samples suppressed the IgG binding in each of the acute TTP patients, but in none of the non-TTP groups. Serial measurement in a patient that had two exacerbations of TTP within the first three weeks revealed that the ADAMTS13 activity levels remained < 0.1 U/ml during this period, and the ADAMTS13-binding IgG remained elevated, suggesting that ADAMTS13 analysis may provide valuable insight to the disease status during the course of therapy. Analysis of ADAMTS13-binding IgG is helpful for the diagnosis and management of TTP.

Keywords

ADAMTS13 - thrombotic thrombocytopenic purpura - antibody

• References

• 1 Bukowski RM. Thrombotic thrombocytopenic purpura A review. Prog Hemost Thromb 1982; 06: 287-337.
• 2 Tsai HM. Current concepts in thrombotic thrombocytopenic purpura. Annu Rev Med 2006; 57: 419-36.
• 3 Furlan M, Robles R, Galbusera M. et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998; 339: 1578-84.
• 4 Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339: 1585-94.
• 5 Tsai HM, Li A, Rock G. Inhibitors of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura. Clin Lab 2001; 47: 387-92.
• 6 Veyradier A, Obert B, Houllier A. et al. Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood 2001; 98: 1765-72.
• 7 Rick ME, Moll S, Taylor MA. et al. Clinical use of a rapid collagen binding assay for von Willebrand factor cleaving protease in patients with thrombotic thrombocytopenic purpura. Thromb Haemost 2002; 88: 598-604.
• 8 Studt JD, Kremer Hovinga JA, Alberio L. et al. Von Willebrand factor-cleaving protease (ADAMTS-13) activity in thrombotic microangiopathies: diagnostic experience 2001/2002 of a single research laboratory. Swiss Med Wkly 2003; 133: 325-32.
• 9 Coppo P, Bengoufa D, Veyradier A. et al. Severe ADAMTS13 deficiency in adult idiopathic thrombotic microangiopathies defines a subset of patients characterized by various autoimmune manifestations, lower platelet count, and mild renal involvement. Medicine (Baltimore) 2004; 83: 233-44.
• 10 Peyvandi F, Ferrari S, Lavoretano S. et al. von Willebrand factor cleaving protease (ADAMTS-13) and ADAMTS-13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura. Br J Haematol 2004; 127: 433-9.
• 11 Zhou W, Tsai HM. An enzyme immunoassay of ADAMTS13 distinguishes patients with thrombotic thrombocytopenic purpura from normal individuals and carriers of ADAMTS13 mutations. Thromb Haemost 2004; 91: 806-11.
• 12 Kokame K, Nobe Y, Kokubo Y. et al. FRETSVWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol 2005; 129: 93-100.
• 13 Zhou W, Inada M, Lee TP. et al. ADAMTS13 is expressed in hepatic stellate cells. Lab Invest 2005; 85: 780-8.
• 14 Zhou W, Dong L, Ginsburg D. et al. Enzymatically active ADAMTS13 variants are not inhibited by antiADAMTS13 autoantibodies: a novel therapeutic strategy?. J Biol Chem 2005; 280: 39934-41.
• 15 Rieger M, Mannucci PM, Hovinga JA. et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood 2005; 106: 1262-7.
• 16 Rock GA, Shumak KH, Buskard NA. et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group.N Engl J Med 1991; 325: 393-7.
• 17 Bohm M, Betz C, Miesbach W. et al. The course of ADAMTS-13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine. Br J Haematol 2005; 129: 644-52.
• 18 Bennett CL, Davidson CJ, Raisch DW. et al. Thrombotic thrombocytopenic purpura associated with ticlopidine in the setting of coronary artery stents and stroke prevention. Arch Intern Med 1999; 159: 2524-8.
• 19 Tsai HM, Rice L, Sarode R. et al. Antibody inhibitors to von Willebrand factor metalloproteinase and increased binding of von Willebrand factor to platelets in ticlopidine-associated thrombotic thrombocytopenic purpura. Ann Intern Med 2000; 132: 794-9.
• 20 Sugio Y, Okamura T, Shimoda K. et al. Ticlopidine-Associated thrombotic thrombocytopenic purpura with an IgG-type inhibitor to von Willebrand factor-cleaving protease activity. Int J Hematol 2001; 74: 347-51.
• 21 Yang CW, Chen YC, Dunn P. et al. Ticlopidine-induced thrombotic thrombocytopenic purpura: two case reports treated with plasma exchange plus steroids. Ren Fail 2001; 23: 851-6.
• 22 Scheiflinger F, Knobl P, Trattner B. et al. Nonneutralizing IgM and IgG antibodies to von Willebrand factor-cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura. Blood 2003; 102: 3241-3.