Search PubMed⌕ Search

PubMed · 1561674

Antiphospholipid cofactor.

Abstract

A plasma protein is required as a cofactor for the binding of antiphospholipid antibodies to phospholipids. This protein has been identified as beta 2-glycoprotein I, an apolipoprotein that binds to negatively charged phospholipids and is a natural inhibitor of the coagulation cascade. It is not certain whether antiphospholipid antibodies bind to beta 2-glycoprotein I alone, to beta 2-glycoprotein I-phospholipid complex, or to a phospholipid epitope modified by beta 2-glycoprotein I. We used isolated beta 2-glycoprotein I and purified IgG and IgM antiphospholipid antibodies from serum or plasma of patients with the antiphospholipid syndrome to study the relation between antiphospholipid antibodies and beta 2-glycoprotein I in enzyme-linked immunosorbent assays. IgG antiphospholipid antibodies did not bind to beta 2-glycoprotein I when it was used as an antigen on the assay plate. The binding of IgG and IgM antiphospholipid antibodies to phospholipid was enhanced when beta 2-glycoprotein I was added to the phospholipid antigens either before or together with the antiphospholipid antibodies. The degree of enhancement varied across patients. IgM antiphospholipid antibodies required less cofactor for binding to phospholipid antigens. These results confirm the requirement of beta 2-glycoprotein I as a cofactor for the binding of autoimmune antiphospholipid antibodies to phospholipids.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A E Gharavi. 1992. Antiphospholipid cofactor.. https://pubmed.ncbi.nlm.nih.gov/1561674/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

ERBB3 overexpression due to miR-205 inactivation confers sensitivity to FGF, metabolic activation, and liability to ERBB3 targeting in glioblastoma.

In glioblastoma (GBM), the most frequent and lethal brain tumor, therapies suppressing recurrently altered signaling pathways failed to extend survival. However, in patient subsets, specific genetic lesions can confer sensitivity to targeted agents. By exploiting an integrated model based on patient-derived stem-like cells, faithfully recapitulating the original GBMs in vitro and in vivo, here, we identify a human GBM subset (∼9% of all GBMs) characterized by ERBB3 overexpression and nuclear accumulation. ERBB3 overexpression is driven by inheritable promoter methylation or post-transcriptional silencing of the oncosuppressor miR-205 and sustains the malignant phenotype. Overexpressed ERBB3 behaves as a specific signaling platform for fibroblast growth factor receptor (FGFR), driving PI3K/AKT/mTOR pathway hyperactivation, and overall metabolic upregulation. As a result, ERBB3 inhibition by specific antibodies is lethal for GBM stem-like cells and xenotransplants. These findings highlight a subset of patients eligible for ERBB3-targeted therapy.

Antibodies↗

Double-blotting: a solution to the problem of non-specific binding of secondary antibodies in immunoblotting procedures.

"Double-blotting" (DB) was developed to overcome the problem of non-specific binding of secondary antibodies in immunoblotting (IB). After it had been probed by the primary antibody, the membrane with the blotted proteins was assembled with a second blank membrane and submitted to a second blotting under acidic conditions. The primary antibody molecules were thus desorbed from their corresponding antigen and transferred onto the second membrane, whereas the antigen and the interfering proteins remained bound to the first one. The second membrane could then be probed by the secondary antibodies without the risk of non-specific binding. This method was developed for the study of erythropoietin (EPO) in concentrated urine since a strong non-specific binding of biotinylated secondary antibodies to some urinary proteins had been observed using classical IB protocols.

Antibodies↗

Comparative study of circulating immune complexes quantity detection by three assays--CIF-ELISA, C1q-ELISA and anti-C3 ELISA.

The assessment of the soluble immune complexes (IC) in human sera is traditionally performed by the C1q binding assay. In the present study, a novel method for the quantity of immune complexes was reported. The methodology was based on measuring their deposition on solid-phase C3 binding glycoprotein (CIF), using an enzyme-linked immunosorbent assay. We also used ELISA that employed anti-C3 antibodies to determined the quantity of immune complexes. The three assays were evaluated for their performance characteristics on the same specially prepared samples: 55 normal sera, 99 sera from RA, 88 sera from SLE, and 27 sera from PSS. The results were compared by reference to a common standard-heat aggregated IgG that possesses many activities of immune complexes. Three of the tests used displayed almost the same specificity (over 95%), while their relative sensitivity varied depending on the disease sera tested. The sensitivity of the assays used was recorded highest for C1q ELISA-28.97% of positive sera, followed by CIF-ELISA-19.63% and lowest for anti-C3 ELISA-17.29%. A well-expressed correlation was found between CIF-ELISA and anti-C3 ELISA data (r=0.42), and a week correlation was noted when comparing CIF-ELISA and C1q ELISA IC levels detected (r=0.28). When the correlation coefficients were calculated individually for each disease category, they were clearly different, and that reflected indirectly in different sensitivities of the test for various disease categories. We also found that the results from the simultaneous performance of the tests demonstrated low percentage positive results when three or two assays were used. This is most probably due to the different assay abilities to detect IC with different sizes and composition, which shows that a small part of IC in the tested sera can be detected simultaneously by more than one assay. On the basis of the results obtained, we concluded that optimal screening for IC could be achieved by parallel application of several different methods.

Antibodies↗