Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP

Robert McMillan; Jennifer Lopez-Dee; Ronald Bowditch

doi:10.1055/s-0037-1615754

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(05): 821-823
DOI: 10.1055/s-0037-1615754

Review Article

Schattauer GmbH

Clonal Restriction of Platelet-associated Anti-GPIIb/IIIa Autoantibodies in Patients with Chronic ITP

Robert McMillan

¹The Scripps Research Institute, La Jolla, California, USA, and the University of Oklahoma, Oklahoma City, Oklahoma, USA

,

Jennifer Lopez-Dee

¹The Scripps Research Institute, La Jolla, California, USA, and the University of Oklahoma, Oklahoma City, Oklahoma, USA

,

Ronald Bowditch

¹The Scripps Research Institute, La Jolla, California, USA, and the University of Oklahoma, Oklahoma City, Oklahoma, USA

› Author Affiliations

Abstract

Summary

Chronic immune thrombocytopenic purpura is due to platelet destruction induced by autoantibodies against platelet surface antigens. Prior studies show that some serum autoantibodies are light-chain restricted, suggesting a clonal origin. Since plasma and platelet-associated antibody from the same patient may bind to different epitopes, it is important to evaluate the clonality of platelet-associated antibody. Platelet-associated autoantibodies from 28 ITP patients were studied. Of 23 platelet-associated antibodies tested directly, 16 showed significant light chain restriction (7 complete and 9 partial) when compared to plasma IgG light chain distribution. Similarly, 9 of 12 platelet-associated antibody eluates were light chain restricted, 5 complete and 4 partial. In all cases where platelet-associated antibody and antibody eluate from the same patient were studied, the results were concordant. We conclude that a significant proportion of platelet-associated antibodies from ITP patients show apparent clonality, as evaluated by light chain restriction. These results are consistent with other studies in ITP suggesting a limited antigenic repertoire.

Keywords

ITP - autoantibody - platelet - clonality

Full Text

References

References
1 George JN, El-Harake MA, Aster RH. Thrombocytopenia due to enhanced platelet destruction by immunologic mechanisms. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ. editors. Williams Hematology. New York: McGraw-Hill; 1995: 1315-5.
2 Karpatkin S. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet 1997; 349: 1531-6.
3 McMillan R, Imbach P. Immune thrombocytopenia. In: Schafer AI, Loscalzo J. editors. Thrombosis and Hemorrhage. Cambridge, MA: Blackwell Scientific Publications, Inc.; 1998: 643-64.
4 Rosse WF, Adams JP, Yount WJ. Subclasses of IgG antibodies in immune thrombocytopenic purpura. Br J Haematol 1980; 46: 109-14.
5 Hymes K, Schur PH, Karpatkin S. Heavy-chain subclass of bound anti-platelet IgG in autoimmune thrombocytopenic purpura. Blood 1980; 56: 84-7.
6 Helmerhorst FM, van Leeuwen EF, Pegels JG. et al. Primary and secondary autoimmune thrombocytopenia. A serological and clinical analysis. Scand J Haematol 1982; 28: 319-28.
7 Gearhart CG, Sigal NH, Klinman NR. Production of antibodies of identical idiotype but diverse immunoglobulin classes by cells derived from a single stimulated B cell. Proc Natl Acad Sci 1975; 72: 1707-11.
8 Sinha RK, Kelton JG. Current controversies concerning the measurement of platelet-associated IgG. Trans Med Rev 1990; 4: 121-35.
9 George JN. Platelet immunoglobulin G: its significance for the evaluation of thrombocytopenia and for understanding the origin of α-granule proteins. Blood 1990; 76: 859-70.
10 Fujisawa K, Tani P, O’Toole TE. et al. Different specificities of platelet-associated and plasma autoantibodies to platelet GPIIb-IIIa in patients with chronic ITP. Blood 1992; 79: 1441-6.
11 Stockelberg D, Hou M, Jacobsson S. et al. Evidence for a light chain restriction of glycoprotein Ib/IX and IIb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura. Br J Haematol 1995; 90: 175-9.
12 Stockelberg D, Hou M, Jacobsson S. et al. Light chain-restricted autoanti-bodies in chronic idiopathic thrombocytopenic purpura, but no evidence for circulating clonal B-lymphocytes. Ann Hematol 1996; 72: 29-34.
13 Christie DJ, Sauro SC, Fairbanks KD, Kay NE. Detection of clonal platelet antibodies in immunologically-mediated thrombocytopenias: association with circulating clonal/oligclonal B cells. Br J Haematol 1993; 85: 277-84.
14 Varon D, Karpatkin S. A monoclonal antiplatelet antibody with decreased reactivity for autoimmune thrombocytopenic platelets. Proc Natl Acad Sci USA 1983; 80: 6992-5.
15 Nugent DJ. Human monoclonal antibodies in the characterization of platelet antigens. In: Kunicki T, George JN. editors. Platelet immunobiology: molecular and clinical aspects. Philadelphia: Lippincott; 1989: 273-90.
16 Hou M, Stockelberg D, Kutti J, Wadenvik H. Glycoprotein IIb/IIIa autoantigenic repertoire in chronic idiopathic thrombcytopenic purpura. Br J Haematol 1995; 91: 971-5.
17 Escher R, Muller D, Vogel M. et al. Recombinant human natural autoanti-bodies against GPIIb/IIIa inhibit binding of autoantibodies from patients with AITP. Br J Haematol 1998; 102: 820-8.
18 He R, Reid DM, Jones CE, Shulman NR. Extracellular epitopes of platelet glycoprotein Iba reactive with serum antibodies from patients with chronic idiopathic thrombocytopenic purpura. Blood 1995; 86: 3789-96.
19 Bye JM, Carter C, Cui Y. et al. Germline variable region gene segment derivation of human monoclonal anti-Rh(D) antibodies. J Clin Invest 1992; 90: 2481-90.
20 Roben P, Barbas SM, Sandoval L. et al. Repertoire cloning of lupus anti-DNA autoantibodies. J Clin Invest 1996; 98: 2827-37.
21 Van der Harst D, de Jong D, Limpens J. et al. Clonal B-cell populations in patients with idiopathic thrombocytopenic purpura. Blood 1990; 76: 2321-6.