PMID- 11522008 OWN - NLM STAT- MEDLINE DCOM- 20020802 LR - 20071114 IS - 0340-6245 (Print) IS - 0340-6245 (Linking) VI - 86 IP - 2 DP - 2001 Aug TI - Beta2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of beta2-glycoprotein I. PG - 590-5 AB - Many of the autoantibodies in antiphospholipid syndrome (APS) are directed against beta2-glycoprotein I (beta2-GPI). Recent studies from our laboratories have indicated that the immunodominant binding epitope(s) for high titer, affinity purified antibodies from 11 APS patients are localized to the amino terminal domain (domain 1) of beta2-GPI. The present study employed surface plasmon resonance to localize the immunodominant domain in serum samples from a large cohort of patients with GPL values ranging from 21 to 230 units (n = 106 patients). Eighty-eight percent of patients showed > or = threefold selectivity for beta2-GPI containing domain 1 relative to the domain deletion mutant that lacked domain 1. The domain 1 binding activity in patient serum was abolished by removing the IgG fraction from the serum and the binding activity could be fully reconstituted with the IgG fraction. Thus, analysis of serum samples from a large cohort of APS patients indicates that the immunodominant binding epitope(s) for anti-beta2 antibodies are localized to the amino terminal domain of beta2-GPI. FAU - McNeeley, P A AU - McNeeley PA AD - La Jolla Pharmaceutical Company, San Diego, CA 92121, USA. FAU - Dlott, J S AU - Dlott JS FAU - Furie, R A AU - Furie RA FAU - Jack, R M AU - Jack RM FAU - Ortel, T L AU - Ortel TL FAU - Triplett, D A AU - Triplett DA FAU - Victoria, E J AU - Victoria EJ FAU - Linnik, M D AU - Linnik MD LA - eng GR - 1 K24 AI01603-01/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Germany TA - Thromb Haemost JT - Thrombosis and haemostasis JID - 7608063 RN - 0 (Antibodies, Anticardiolipin) RN - 0 (Autoantibodies) RN - 0 (Epitopes) RN - 0 (Glycoproteins) RN - 0 (Immunoglobulin G) RN - 0 (beta 2-Glycoprotein I) SB - IM MH - Adult MH - Antibodies, Anticardiolipin/*immunology/metabolism MH - Antibody Affinity MH - Antibody Specificity MH - Antiphospholipid Syndrome/immunology MH - Autoantibodies/analysis/immunology MH - Case-Control Studies MH - Cohort Studies MH - Epitopes/analysis/chemistry/metabolism MH - Female MH - Glycoproteins/*immunology/metabolism MH - Humans MH - Immunoglobulin G/analysis/immunology MH - Male MH - Middle Aged MH - Protein Structure, Tertiary MH - Surface Plasmon Resonance MH - beta 2-Glycoprotein I EDAT- 2001/08/28 10:00 MHDA- 2002/08/03 10:01 CRDT- 2001/08/28 10:00 PHST- 2001/08/28 10:00 [pubmed] PHST- 2002/08/03 10:01 [medline] PHST- 2001/08/28 10:00 [entrez] AID - 01080590 [pii] PST - ppublish SO - Thromb Haemost. 2001 Aug;86(2):590-5.