Relative importance of different human aPL derived heavy and light chains in the binding of aPL to cardiolipin

Giles, Ian; Haley, Joanna; Nagl, Sylvia; Latchman, David S.; Chen, Pojen P.; Chukwuocha, Reginald U.; Isenberg, David; Rahman, Anisur

doi:10.1016/s0161-5890(03)00100-7

Cited by 25 publications

(37 citation statements)

References 47 publications

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“…Stored serum taken immediately prior to BCDT (time 0) and 6–9 months post depletion was analysed for the presence of IgG antibodies to cardiolipin, β2-glycoprotein I (β 2 GPI) and the domain I portion of β 2 GPI, which has recently been described as being particularly associated with pathogenicity 9 10. Assays were performed as described previously 10 11. We used our standard BCDT regimen for SLE patients of 1 g of rituximab given twice, 2 weeks apart.…”

Section: Methodsmentioning

confidence: 99%

B cell depletion therapy for patients with systemic lupus erythaematosus results in a significant drop in anticardiolipin antibody titres

Ioannou

Lambrianides

Cambridge

et al. 2007

Annals of the Rheumatic Diseases

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Section: Methodsmentioning

confidence: 99%

B cell depletion therapy for patients with systemic lupus erythaematosus results in a significant drop in anticardiolipin antibody titres

Ioannou

Lambrianides

Cambridge

et al. 2007

Annals of the Rheumatic Diseases

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“…Constructs containing the wild-type heavy chain and light chain were prepared as detailed fully in previous articles [29,35]. UK4V H could not be cloned into the appropriate plasmid, hence only UK4V L was available for analysis.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously described a system for the in vitro expression of whole IgG molecules from cloned V H and V L sequences of human monoclonal aPL antibodies [29]. This system was used to test the binding properties of combinations of heavy chains and light chains derived from a range of human antibodies.…”

Section: Introductionmentioning

confidence: 99%

“…We found that the sequence of IS4V H was dominant in conferring the ability to bind cardiolipin (CL) while the identity of the V L paired with this heavy chain was important in determining the strength of CL binding [29]. …”

Section: Introductionmentioning

confidence: 99%

“…The CDR3 region of IS4V H contains five arginine residues, of which four are predicted by the model to be surface-exposed, and therefore is potentially important in binding to CL [29]. …”

Section: Introductionmentioning

confidence: 99%

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et al. 2005

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Previously we reported that the variable heavy chain region (V H ) of a human beta 2 glycoprotein I-dependent monoclonal antiphospholipid antibody (IS4) was dominant in conferring the ability to bind cardiolipin (CL). In contrast, the identity of the paired variable light chain region (V L ) determined the strength of CL binding. In the present study, we examine the importance of specific arginine residues in IS4V H and paired V L in CL binding. The distribution of arginine residues in complementarity determining regions (CDRs) of V H and V L sequences was altered by site-directed mutagenesis or by CDR exchange. Ten different 2a2 germline gene-derived V L sequences were expressed with IS4V H and the V H of an anti-dsDNA antibody, B3. Six variants of IS4V H , containing different patterns of arginine residues in CDR3, were paired with B3V L and IS4V L . The ability of the 32 expressed heavy chain/light chain combinations to bind CL was determined by ELISA. Of four arginine residues in IS4V H CDR3 substituted to serines, two residues at positions 100 and 100 g had a major influence on the strength of CL binding while the two residues at positions 96 and 97 had no effect. In CDR exchange studies, V L containing B3V L CDR1 were associated with elevated CL binding, which was reduced significantly by substitution of a CDR1 arginine residue at position 27a with serine. In contrast, arginine residues in V L CDR2 or V L CDR3 did not enhance CL binding, and in one case may have contributed to inhibition of this binding. Subsets of arginine residues at specific locations in the CDRs of heavy chains and light chains of pathogenic antiphospholipid antibodies are important in determining their ability to bind CL.

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Preparation and characterization of organic–inorganic hybrid composites based on multiepoxy silsesquioxane and cyanate resin

Liang

Guo

2006

J of Applied Polymer Sci

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A multiepoxy cubic silsesquioxane was prepared by the hydrolysis and polycondensation of trifunctional monomer (␥-glycidoxypropyl)trimethoxysilane in a solvent mixture of methyl isobutyl ketone and anhydrous ethanol with a tetraethyl ammonium hydroxide aqueous solution acting as the catalyst, and it was successfully introduced into a cyanate resin and formed highly crosslinked organic-inorganic hybrid composites on a molecular level via a mutual cure reaction. The properties of the multiepoxy cubic silsesquioxane/bisphenol A dicyanate ester resin composites were investigated, and the results showed that introducing the cubic silsesquioxane unit into the cyanate resin successfully modified the local structure of the molecule, made the chain more rigid, restricted the chain mobility, and eventually improved the thermal stability and flame retardancy of the resin.

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Relative importance of different human aPL derived heavy and light chains in the binding of aPL to cardiolipin

Cited by 25 publications

References 47 publications

B cell depletion therapy for patients with systemic lupus erythaematosus results in a significant drop in anticardiolipin antibody titres

B cell depletion therapy for patients with systemic lupus erythaematosus results in a significant drop in anticardiolipin antibody titres

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Preparation and characterization of organic–inorganic hybrid composites based on multiepoxy silsesquioxane and cyanate resin

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