Characterization of IgG monoclonal anti‐cardiolipin/anti‐β<sub>2</sub>GP1 antibodies from two patients with antiphospholipid syndrome reveals three species of antibodies

Zhu, Min; Olee, Tsaiwei; Le, Dzung; Roubey, Robert; Hahn, Bevra H.; Woods, Virgil L.; Chen, Pojen P.

doi:10.1111/j.1365-2141.1999.01292.x

Cited by 79 publications

(78 citation statements)

References 44 publications

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“…Zhu et al (40) reported 2 human IgG monoclonal antibodies, IS1 and IS2, that bound bovine but not human ␤ 2 GPI. Sequence analysis later showed that these antibodies were derived from the same B cell clone (41).…”

Section: Lambrianides Et Almentioning

confidence: 99%

Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

Lambrianides¹,

Giles²,

Ioannou³

et al. 2007

Arthritis & Rheumatism

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Objective. Previous studies have shown the importance of somatic mutations and arginine residues in the complementarity-determining regions (CDRs) of pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies in human and murine lupus, and in studies of murine antibodies, a role of mutations at position 53 in V H CDR2 has been demonstrated. We previously demonstrated in vitro expression and mutagenesis of the human IgG1 monoclonal antibody B3. The present study was undertaken to investigate, using this expression system, the importance of the arginine residue at position 53 (R53) in B3 V H .Methods. R53 was altered, by site-directed mutagenesis, to serine, asparagine, or lysine, to create 3 expressed variants of V H . In addition, the germline sequence of the V H 3-23 gene (from which B3 V H is derived) was expressed either with or without arginine at position 53. These 5 new heavy chains, as well as wild-type B3 V H , were expressed with 4 different light chains, and the resulting antibodies were assessed for their ability to bind to nucleosomes, ␣-actinin, cardiolipin, ovalbumin, ␤ 2 -glycoprotein I (␤ 2 GPI), and the N-terminal domain of ␤ 2 GPI (domain I), using direct binding assays.Results. The presence of R53 was essential but not sufficient for binding to dsDNA and nucleosomes. Conversely, the presence of R53 reduced binding to ␣-actinin, ovalbumin, ␤ 2 GPI, and domain I of ␤ 2 GPI. The combination B3 (R53S) V H /B3 V L bound human, but not bovine, ␤ 2 GPI.Conclusion. The fact that the R53S substitution significantly alters binding of B3 to different clinically relevant antigens, but that the alteration is in opposite directions depending on the antigen, implies that this arginine residue plays a critical role in the affinity maturation of antibody B3.

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Section: Lambrianides Et Almentioning

confidence: 99%

Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

Lambrianides¹,

Giles²,

Ioannou³

et al. 2007

Arthritis & Rheumatism

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“…Anti-cardiolipin mAbs IS4 and IS6 were derived from an APS patient and hybridomas and were generated as described (29). The CD4 inducible anti-HIV-1 gp120 mAb 17b (30,31) was provided by Dr. J. Robinson (Tulane University, New Orleans, LA).…”

Section: Antibodiesmentioning

confidence: 99%

The Role of Antibody Polyspecificity and Lipid Reactivity in Binding of Broadly Neutralizing Anti-HIV-1 Envelope Human Monoclonal Antibodies 2F5 and 4E10 to Glycoprotein 41 Membrane Proximal Envelope Epitopes

Alam

McAdams

Boren

et al. 2007

The Journal of Immunology

239

328

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Two neutralizing human mAbs, 2F5 and 4E10, that react with the HIV-1 envelope gp41 membrane proximal region are also polyspecific autoantibodies that bind to anionic phospholipids. To determine the autoantibody nature of these Abs, we have compared their reactivities with human anti-cardiolipin mAbs derived from a primary antiphospholipid syndrome patient. To define the role of lipid polyreactivity in binding of 2F5 and 4E10 mAbs to HIV-1 envelope membrane proximal epitopes, we determined the kinetics of binding of mAbs 2F5 and 4E10 to their nominal gp41 epitopes vs liposome-gp41 peptide conjugates. Both anti-HIV-1 mAbs 2F5 and 4E10 bound to cardiolipin with Kd values similar to those of autoimmune anti-cardiolipin Abs, IS4 and IS6. Binding kinetics studies revealed that mAb 2F5 and 4E10 binding to their respective gp41 peptide-lipid conjugates could best be defined by a two-step (encounter-docking) conformational change model. In contrast, binding of 2F5 and 4E10 mAbs to linear peptide epitopes followed a simple Langmuir model. A mouse mAb, 13H11, that cross-blocks mAb 2F5 binding to the gp41 epitope did not cross-react with lipids nor did it neutralize HIV-1 viruses. Taken together, these data demonstrate the similarity of 2F5 and 4E10 mAbs to known anti-cardiolipin Abs and support the model that mAb 2F5 and 4E10 binding to HIV-1 involves both viral lipid membrane and gp41 membrane proximal epitopes.

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“…IgG fractions from APS patients (APS-IgG) and control sera of SLE patients without APS (SLE-IgG) and healthy subjects (normal controls (NC-IgG) were purified on protein G columns (HiTrap Protein G; Pharmacia Biotech, Uppsala, Sweden). Two mAbs against cardiolipin (CL) (CL15 and IS4) were derived from EBV-transformed cell lines from two APS patients, whose clinical and serologic characteristics have previously been described (43). CL15 and IS4 were generated as the conventional aCL (by being screened against CL in the presence of bovine serum).…”

Section: Patients Blood Samples and Isolation Of Iggmentioning

confidence: 99%

Antiphospholipid Antibodies Induce Monocyte Chemoattractant Protein-1 in Endothelial Cells

Cho

Chen

et al. 2002

The Journal of Immunology

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The presence of antiphospholipid Ab is associated with increased risk of thrombosis. The monocyte-endothelial cell interaction has been suggested to play a key role at the site of vascular injury during thrombosis. Therefore, we tested the effect of anticardiolipin Abs (aCL) on the production of monocyte chemoattractant protein-1 (MCP-1) in HUVEC. We found that monoclonal aCL as well as IgG fractions from patients with antiphospholipid syndrome (APS-IgG) could induce the production of MCP-1 in HUVEC. The ability of IgG aCL to induce MCP-1 production could be abrogated by preabsorption with cardiolipin liposomes. Simultaneous addition of either monoclonal aCL or APS-IgG with IL-1β resulted in synergistic increase in MCP-1 production, whereas the addition of control IgG lacking aCL activity did not alter IL-1β-induced levels of MCP-1. MCP-1 mRNA expression was also up-regulated when HUVEC were incubated with either APS-IgG or monoclonal aCL, and down-regulated by the treatment of dexamethasone. In addition, we found that serum levels of MCP-1 in 76 systemic lupus erythematosus patients correlated well with the titers of IgG aCL. Collectively, these results indicate that aCL could promote endothelial cell-monocyte cross-talk by enhancing the endothelial production of MCP-1, thereby shifting the hemostatic balance toward the prothrombotic state of APS.

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Characterization of IgG monoclonal anti‐cardiolipin/anti‐β₂GP1 antibodies from two patients with antiphospholipid syndrome reveals three species of antibodies

Cited by 79 publications

References 44 publications

Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

The Role of Antibody Polyspecificity and Lipid Reactivity in Binding of Broadly Neutralizing Anti-HIV-1 Envelope Human Monoclonal Antibodies 2F5 and 4E10 to Glycoprotein 41 Membrane Proximal Envelope Epitopes

Antiphospholipid Antibodies Induce Monocyte Chemoattractant Protein-1 in Endothelial Cells

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Characterization of IgG monoclonal anti‐cardiolipin/anti‐β2GP1 antibodies from two patients with antiphospholipid syndrome reveals three species of antibodies

Cited by 79 publications

References 44 publications

Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

The Role of Antibody Polyspecificity and Lipid Reactivity in Binding of Broadly Neutralizing Anti-HIV-1 Envelope Human Monoclonal Antibodies 2F5 and 4E10 to Glycoprotein 41 Membrane Proximal Envelope Epitopes

Antiphospholipid Antibodies Induce Monocyte Chemoattractant Protein-1 in Endothelial Cells

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Characterization of IgG monoclonal anti‐cardiolipin/anti‐β₂GP1 antibodies from two patients with antiphospholipid syndrome reveals three species of antibodies