Disease relevance of Apoh

• Autoantibodies against oxLDL/beta(2)GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) and significantly correlate with arterial thrombosis [1].
• beta 2-Glycoprotein I, a serum protein with in vitro anticoagulant properties, plays a vital role in the binding of "anticardiolipin" antibodies purified from patients with autoimmune disease in a cardiolipin ELISA [2].
• Together these data are consistent with pathogenic mechanisms in antiphospholipid syndrome involving both neutralization of beta(2)GPI function and beta(2)GPI-immunoglobulin complex formation [3].
• Thus, the immune response towards beta2-GPI may play an important role in atherogenesis, serving as a possible target for antigen specific therapies [4].
• However, there was an 18% reduction in the number of viable implantation sites in beta(2)GPI-/- mice and reduced fetal weight and fetal:placental weight ratio in late gestation, suggesting compromised placental function [3].

High impact information on Apoh

• Anticardiolipin antibodies (aCL) derived from the sera of individuals exhibiting the antiphospholipid syndrome (APS) directly bind to beta 2-glycoprotein I (beta 2-GPI), which is adsorbed to an oxidized polystyrene surface [5].
• Antibody binding to beta 2-GPI on the irradiated plates was competitively inhibited by simultaneous addition of cardiolipin (CL)-coated latex beads mixed together with beta 2-GPI but were unaffected by addition of excess beta 2-GPI, CL micelles, or CL-coated latex beads alone [5].
• beta2-Glycoprotein I (beta2GPI), a plasma glycoprotein with phospholipid-binding property, is known to be the actual target antigen for autoimmune type anticardiolipin antibodies (aCLs) [6].
• Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I [7].
• Induction of early atherosclerosis in LDL-receptor-deficient mice immunized with beta2-glycoprotein I [8].

Chemical compound and disease context of Apoh

• Phosphatidylserine expression on cell surfaces promotes antibody-dependent aggregation and thrombosis in beta2-glycoprotein I-immune mice [9].
• Both hexagonal (II) phosphatidylethanolamine and the cardiolipin/apolipoprotein H mixture were capable of inducing aPL with lupus anticoagulant activity [10].

Biological context of Apoh

• Molecular cloning of mouse beta 2-glycoprotein I and mapping of the gene to chromosome 11 [11].
• The amino acid sequence deduced from the nucleotide sequence of mouse beta 2 GPI revealed 76.1% identity with that of human beta 2 GPI [11].
• The transcription start site was identified by primer extension 44 nucleotides upstream of the initiator AUG codon. beta 2-Glycoprotein I consists of repeated domains that correspond well to the exon/intron structure of the gene [2].
• The gene (ApoH) encoding the mouse beta 2-glycoprotein I, including 5' and 3' flanking sequences, has been isolated and characterized [2].
• beta(2)-Glycoprotein I (beta(2)GPI) is a principal target antigen for antiphospholipid antibodies associated with recurrent pregnancy loss and fetal growth restriction in women [3].

Anatomical context of Apoh

• Evidence for anticoagulant activity and beta2-GPI accumulation in late endosomes of endothelial cells induced by anti-LBPA antibodies [12].
• WB-CAL-1 significantly increased the in vitro uptake of oxLDL/beta(2)GPI complexes by macrophages [1].
• When human plaques were studied, it was found that beta2-GPI resides in the subendothelial regions and co-localizes with CD4 lymphocytes [4].
• Furthermore, anti5H9 inhibits both the recombinant beta2-glycoprotein I- and the recall antigen tetanus toxoid-specific T cell proliferation [13].
• These results suggest that thrombosis in antiphospholipid syndrome could, in part, be due to antibody-dependent cross-linking of beta2GP1 bound to PS-expressing cells and the vascular endothelium [9].

Associations of Apoh with chemical compounds

• beta 2-glycoprotein I (beta 2I) is a 50kDa serum glycoprotein of ill defined function [14].
• Binding of beta2-GPI to solid-phase cardiolipin (CL) was diminished by the deletion of the fifth domain (domain V) from its complete structure [15].
• We show that 3G4 enhances binding of beta2GP1 to EC induced to expose PS [16].
• 3. Aggregation and secretion induced by MAbs plus beta 2 GPI did not require exogenous fibrinogen and were variably inhibited in the presence of acetyl salicylic acid, apyrase or Ca2+, depending on the concentrations used for the two proteins.(ABSTRACT TRUNCATED AT 250 WORDS)[17]
• Bilayer phosphatidylethanolamine and cardiolipin in the absence of apolipoprotein H were nonimmunogenic [10].

Other interactions of Apoh

• In addition, Abs against beta2 glycoprotein I restore local and remote tissue damage in the Cr2(-/-) mice [18].
• Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with beta 2-glycoprotein I [19].
• These antibodies are heterogeneous and react against phospholipid-binding proteins such as beta2-glycoprotein I (beta2GPI) and prothrombin [20].
• beta 2-Glycoprotein I (beta 2GPI) is a 50 kDa molecule proposed as a principal target of 'autoimmune' antiphospholipid antibodies (aPL) [21].
• We examined cytosolic chaperonin theta subunit (CCTtheta), Ngg1 interacting factor 3 like 1 binding protein 1 (NIF3L1 BP1) and apolipoprotein H (ApoH) expression during mouse onto-geny using RT-PCR [22].

Analytical, diagnostic and therapeutic context of Apoh

• IgG autoantibodies having similar specificity emerged spontaneously in non-immunized NZWxBXSB F1 mice, an animal model of APS, and a monoclonal autoantibody (WB-CAL-1; IgG2a) against complexed beta(2)GPI (oxLDL/beta(2)GPI complexes) was derived from the same mice [1].
• The reactivity of HCAL to cardiolipin and to beta2-glycoprotein I (beta2GPI) was studied using a solid-phase enzyme immunoassay [23].
• Analysis of PS vesicles recovered from immune mice by sequencing and Western blotting showed the presence of bound beta2GP1 and autologous antibody, respectively [9].
• These data point to the ability of beta-2-GPI to induce pathogenic anti-cardiolipin antibodies following active immunization [24].
• The interaction between five murine monoclonal antibodies (mAb) and beta2-glycoprotein I (beta2GPI) in the absence of phospholipids was studied using surface plasmon resonance-based biosensor technology [25].

References