Characterization of binding of human β2-glycoprotein I to cardiolipin

beta 2-Glycoprotein I-cardiolipin complexes are reported to be a target antigen for the binding of a subset of anti-phospholipid antibodies. The characteristics of binding of beta 2-glycoprotein I to cardiolipin are reported in this paper. Binding at neutral pH is specific, saturable, dependent on ionic strength and independent of bivalent cation. Binding at low pH is qualitatively different from that at neutral pH, and is not dependent on ionic strength. Denaturation of beta 2-glycoprotein I by heat inactivation and reduction/alkylation indicates that beta 2-glycoprotein I-cardiolipin interaction does not require the native three-dimensional structure of beta 2-glycoprotein I, implying that a linear sequence motif may be responsible. Modification of amino acid residues by KCNO treatment completely destroys binding capacity, indicating crucial involvement of lysine residues in binding of beta 2-glycoprotein I to cardiolipin. Complement factor H, which has some similar highly charged linear sequence motifs to beta 2-glycoprotein I and is composed of the same type of protein module, was found to bind to cardiolipin and inhibit the binding of beta 2-glycoprotein I to cardiolipin. Three different lysine-rich segments of the fifth domain of beta 2-glycoprotein I may be involved in binding to cardiolipin.

Download Full-text

Lack of Functional Similarity Between Complement Factor H and Anticardiolipin Cofactor, beta2-Glycoprotein I (Apolipoprotein H)

Scandinavian Journal of Immunology ◽

10.1111/j.1365-3083.1995.tb03694.x ◽

1995 ◽

Vol 42 (5) ◽

pp. 547-550 ◽

Cited By ~ 6

Author(s):

M. PUURUNEN ◽

S. JOKIRANTA ◽

O. VAARALA ◽

S. MERI

Keyword(s):

Factor H ◽

Functional Similarity ◽

Complement Factor H ◽

Complement Factor ◽

Glycoprotein I ◽

Apolipoprotein H

Download Full-text

Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

Clinical Chemistry ◽

10.1373/clinchem.2007.089144 ◽

2007 ◽

Vol 53 (10) ◽

pp. 1792-1799 ◽

Cited By ~ 110

Author(s):

Bevin Gangadharan ◽

Robin Antrobus ◽

Raymond A Dwek ◽

Nicole Zitzmann

Keyword(s):

Hepatitis C ◽

Liver Fibrosis ◽

Liver Biopsy ◽

Factor H ◽

Complement Factor ◽

Related Protein ◽

Serum Samples ◽

Complement Components ◽

Glycoprotein I ◽

Control Serum

Abstract Background: Liver biopsy is currently the gold standard for assessing liver fibrosis, and no reliable noninvasive diagnostic approach is available. Therefore a suitable serologic biomarker of liver fibrosis is urgently needed. Methods: We used a proteomics method based on 2-dimensional gel electrophoresis to identify potential fibrosis biomarkers. Serum samples from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) were analyzed and compared with serum from healthy controls. Results: We observed the most prominent differences when we compared serum samples from cirrhotic patients with healthy control serum. Inter-α-trypsin inhibitor heavy chain H4 (ITIH4) fragments, α1 antichymotrypsin, apolipoprotein L1 (Apo L1), prealbumin, albumin, paraoxonase/arylesterase 1, and zinc-α2-glycoprotein were decreased in cirrhotic serum, whereas CD5 antigen-like protein (CD5L) and β2 glycoprotein I (β2GPI) were increased. In general, α2 macroglobulin (a2M) and immunoglobulin components increased with hepatic fibrosis, whereas haptoglobin and complement components (C3, C4, and factor H-related protein 1) decreased. Novel proteins associated with HCV-induced fibrosis included ITIH4 fragments, complement factor H-related protein 1, CD5L, Apo L1, β2GPI, and thioester-cleaved products of a2M. Conclusions: Assessment of hepatic scarring may be performed with a combination of these novel fibrosis biomarkers, thus eliminating the need for liver biopsy. Further evaluation of these candidate markers needs to be performed in larger patient populations. Diagnosis of fibrosis during early stages will allow early treatment, thereby preventing fibrosis progression.

Download Full-text