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Anti-beta 2-glycoprotein I autoantibodies from patients with the "antiphospholipid" syndrome bind to beta 2-glycoprotein I with low affinity: dimerization of beta 2-glycoprotein I induces a significant increase in anti-beta 2-glycoprotein I antibody affinity.
J Immunol. 1998 Aug 15; 161(4):2038-43.JI

Abstract

"Antiphospholipid" autoantibodies are associated with arterial and venous thrombosis, recurrent fetal loss, and thrombocytopenia. At present, the best-characterized antigenic target for these autoantibodies (or Abs) is the phospholipid-binding protein beta2-glycoprotein I (beta2GPI). These Abs bind beta2GPI only in the presence of negatively charged phospholipids or microtiter polystyrene plates that have been specially treated to give the surface a negative charge. To determine whether the binding of these Abs to beta2GPI on negatively charged surfaces is dependent on increased density or neo-epitopes formed as a consequence of a conformational change on beta2GPI, we generated mutants of beta2GPI by site-directed mutagenesis and assessed the binding characteristics of anti-beta2GPI Abs to these mutants. Our results demonstrate that mutant F307*, which spontaneously forms significant dimerization, is bound best by all the anti-beta2GPI Abs in an anti-beta2GPI ELISA using irradiated polystyrene microtiter plates. In addition, these Abs bound mutant F307* coated onto standard polystyrene microtiter wells in the absence of phospholipid, whereas there was minimal binding with wild-type and mutant F307*/C288A, which formed minimal dimerization. Affinity-purified anti-beta2GPI Abs from patients with the antiphospholipid syndrome demonstrated significantly higher binding affinity for mutant F307* in fluid phase than for wild-type or mutant F307*/C288A of beta2GPI. These results demonstrate that autoantibody binding to beta2GPI is intrinsically of low affinity and that the binding is dependent on the density of the Ag and not on neo-epitope formation.

Authors+Show Affiliations

Department of Medicine, University of New South Wales, St. George Hospital, Sydney, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9712077

Citation

Sheng, Y, et al. "Anti-beta 2-glycoprotein I Autoantibodies From Patients With the "antiphospholipid" Syndrome Bind to Beta 2-glycoprotein I With Low Affinity: Dimerization of Beta 2-glycoprotein I Induces a Significant Increase in Anti-beta 2-glycoprotein I Antibody Affinity." Journal of Immunology (Baltimore, Md. : 1950), vol. 161, no. 4, 1998, pp. 2038-43.
Sheng Y, Kandiah DA, Krilis SA. Anti-beta 2-glycoprotein I autoantibodies from patients with the "antiphospholipid" syndrome bind to beta 2-glycoprotein I with low affinity: dimerization of beta 2-glycoprotein I induces a significant increase in anti-beta 2-glycoprotein I antibody affinity. J Immunol. 1998;161(4):2038-43.
Sheng, Y., Kandiah, D. A., & Krilis, S. A. (1998). Anti-beta 2-glycoprotein I autoantibodies from patients with the "antiphospholipid" syndrome bind to beta 2-glycoprotein I with low affinity: dimerization of beta 2-glycoprotein I induces a significant increase in anti-beta 2-glycoprotein I antibody affinity. Journal of Immunology (Baltimore, Md. : 1950), 161(4), 2038-43.
Sheng Y, Kandiah DA, Krilis SA. Anti-beta 2-glycoprotein I Autoantibodies From Patients With the "antiphospholipid" Syndrome Bind to Beta 2-glycoprotein I With Low Affinity: Dimerization of Beta 2-glycoprotein I Induces a Significant Increase in Anti-beta 2-glycoprotein I Antibody Affinity. J Immunol. 1998 Aug 15;161(4):2038-43. PubMed PMID: 9712077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-beta 2-glycoprotein I autoantibodies from patients with the "antiphospholipid" syndrome bind to beta 2-glycoprotein I with low affinity: dimerization of beta 2-glycoprotein I induces a significant increase in anti-beta 2-glycoprotein I antibody affinity. AU - Sheng,Y, AU - Kandiah,D A, AU - Krilis,S A, PY - 1998/8/26/pubmed PY - 1998/8/26/medline PY - 1998/8/26/entrez SP - 2038 EP - 43 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 161 IS - 4 N2 - "Antiphospholipid" autoantibodies are associated with arterial and venous thrombosis, recurrent fetal loss, and thrombocytopenia. At present, the best-characterized antigenic target for these autoantibodies (or Abs) is the phospholipid-binding protein beta2-glycoprotein I (beta2GPI). These Abs bind beta2GPI only in the presence of negatively charged phospholipids or microtiter polystyrene plates that have been specially treated to give the surface a negative charge. To determine whether the binding of these Abs to beta2GPI on negatively charged surfaces is dependent on increased density or neo-epitopes formed as a consequence of a conformational change on beta2GPI, we generated mutants of beta2GPI by site-directed mutagenesis and assessed the binding characteristics of anti-beta2GPI Abs to these mutants. Our results demonstrate that mutant F307*, which spontaneously forms significant dimerization, is bound best by all the anti-beta2GPI Abs in an anti-beta2GPI ELISA using irradiated polystyrene microtiter plates. In addition, these Abs bound mutant F307* coated onto standard polystyrene microtiter wells in the absence of phospholipid, whereas there was minimal binding with wild-type and mutant F307*/C288A, which formed minimal dimerization. Affinity-purified anti-beta2GPI Abs from patients with the antiphospholipid syndrome demonstrated significantly higher binding affinity for mutant F307* in fluid phase than for wild-type or mutant F307*/C288A of beta2GPI. These results demonstrate that autoantibody binding to beta2GPI is intrinsically of low affinity and that the binding is dependent on the density of the Ag and not on neo-epitope formation. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9712077/Anti_beta_2_glycoprotein_I_autoantibodies_from_patients_with_the_"antiphospholipid"_syndrome_bind_to_beta_2_glycoprotein_I_with_low_affinity:_dimerization_of_beta_2_glycoprotein_I_induces_a_significant_increase_in_anti_beta_2_glycoprotein_I_antibody_affinity_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9712077 DB - PRIME DP - Unbound Medicine ER -