Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rabbit immunized with beta 2-glycoprotein I (beta 2-GPI) produced Abs that bind to negatively charged phospholipids and to beta 2-GPI. After affinity purification of the Abs to beta 2-GPI, the dual reactivity could still be detected. Adsorption studies with a phosphatidylserine affinity column depleted phospholipid-reactive Abs, but beta 2-GPI reactivity was retained. The same pattern of reactivity was found with culture supernatants from rabbit anti-beta 2-GPI splenocytes fused with an immortalized rabbit cell line. The reactivity to negatively charged phospholipids is likely to involve ionic interactions, as high ionic strength buffers eliminated binding to anionic phospholipids, but not to beta 2-GPI. Affinity-purified anti-phospholipid (aPL) Abs from four of seven autoimmune patients bound anionic phospholipids in the absence of beta 2-GPI. However, in high ionic strength buffer, this binding was abolished in three patients and significantly reduced in the fourth. In contrast, affinity-purified aPL Abs from seven autoimmune patients bound to beta 2-GPI-coated plates, and binding in high ionic strength buffer was reduced only moderately in three patients. Therefore, autoimmune-type aPL Abs display anti-beta 2-GPI reactivity and charge-dependent binding to anionic phospholipids similar to affinity-purified rabbit anti-beta 2-GPI Abs.
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PMID:Immunization of a rabbit with beta 2-glycoprotein I induces charge-dependent crossreactive antibodies that bind anionic phospholipids and have similar reactivity as autoimmune anti-phospholipid antibodies. 760 71

The antigenic specificity of anti-phospholipid antibodies (APA) is a matter of intensive investigation. To further characterize these antibodies, we attempted to isolate human monoclonal APA. B-cells of patients with at least one positive test for antibodies against cardiolipin, phosphatidylserine, beta2-glycoprotein I (beta2-GPI) or the lupus anti-coagulant were immortalized by transformation with Epstein-Barr virus and screened for production of specific IgG. Positive pools were fused with a heteromyeloma cell line and APA-secreting clones were isolated by standard procedures. Two monoclonal APA, HL-5B from a 51-year-old man with primary anti-phospholipid syndrome and recurrent cerebral microinfarctions, and RR-7F from a 48-year-old women with systemic lupus erythematosus but no evidence for thrombotic events were obtained. HL-5B is of the IgG2 subtype with lambda light chains, while RR-7F is IgG2 with kappa light chains. Both monoclonals show reactivity against cardiolipin and phosphatidylserine but lack reactivity against beta2-GPI or lupus anti-coagulant activity. To yield the same OD in the cardiolipin and phosphatidylserine ELISAs RR-7F must be used in an approximately 10-fold higher concentration than HL-5B, indicating a lower affinity towards these antigens. Interestingly, both mAPA can bind to cardiolipin in the absence of beta2-GPI. They do not cross-react with dsDNA but show reactivity against oxidized low-density lipoproteins. Analysis of the heavy chain mRNA of HL-5B and RR-7F showed that both are members of the VH3 family. While HL-5B shows extensive somatic mutations in the CDR1 and 2 regions, indicating that it was derived by a T cell-dependent antigen driven process, RR-7F is apparently germline encoded. The two monoclonal APA can be used as tools in further structural and functional analyses.
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PMID:Isolation and characterization of two human monoclonal anti-phospholipid IgG from patients with autoimmune disease. 1047 90

Human beta2-glycoprotein I (beta2gpI) is a phospholipid and heparin binding plasma glycoprotein involved in autoimmune diseases characterized by blood clotting disturbances (thrombosis) together with the occurrence of autoantibodies against beta2gpI. With the final goal of assessing autoantibody influence on binding interactions of beta2gpI we have studied the development of capillary electrophoresis (CE)-based assays for interactions of negatively charged ligands with beta2gpI. In the development of suitable conditions for analysis at neutral pH of this basic protein (pI about 8) we found the pH hysteresis behavior of fused silica surfaces useful since the protonated surface after an acid pre-wash counteracted protein adsorption efficiently in contrast to more laborious procedures including acrylamide/dimethylacrylamide coatings that did not permit analysis of this particular protein. This simple approach made estimates of heparin-beta2gpI interactions possible and the principle was shown also to work for detection of betagpI binding to anionic phospholipids. Utilizing the pH hysteresis effect may be a simple solution to the adsorption problems often encountered in analyses of proteins by CE.
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PMID:Capillary electrophoresis-based analysis of phospholipid and glycosaminoglycan binding by human beta2-glycoprotein I. 1562 44