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Dive into the research topics where J G Gilles is active.

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Featured researches published by J G Gilles.


Journal of Clinical Investigation | 1994

Healthy subjects produce both anti-factor VIII and specific anti-idiotypic antibodies.

J G Gilles; Jean-Marie Saint-Remy

Anti-Factor VIII (FVIII) antibodies were prepared by a combination of salt precipitation, gel filtration chromatography, and specific adsorption over insolubilized FVIII from the serum of 10 healthy subjects with normal levels of FVIII. Antibody specificity was confirmed by the capacity to recognize soluble and insolubilized FVIII and to neutralize FVIII cofactor activity in FX activation. Epitope mapping was carried out using a competition ELISA in which affinity-purified human antibodies inhibited the binding of labeled monoclonal antibodies. In most cases, a single region of the A3 domain of the FVIII light chain was recognized by the antibodies, while the reactivity toward heavy chain epitopes differed from one antibody preparation to the other. Sera or IgG fractions of the serum before immunoadsorption over insolubilized FVIII did not bind to FVIII. The IgG fraction that was not retained on the FVIII immunosorbent contained IgG that bound to the variable part of anti-FVIII mouse monoclonal antibodies and inhibited the binding of labeled FVIII; in addition, the IgG fraction inhibited the binding of affinity-purified human antibodies to FVIII, thereby strongly suggesting the presence of anti-idiotypic antibodies. These findings indicate that the presence of anti-FVIII antibodies is a more universal phenomenon than previously thought and that anti-idiotypic antibodies capable of inhibiting the binding of anti-FVIII antibodies to FVIII are produced spontaneously.


Journal of Clinical Investigation | 1996

Neutralizing antiidiotypic antibodies to factor VIII inhibitors after desensitization in patients with hemophilia A.

J G Gilles; Benoît Desqueper; H Lenk; Jozef Vermylen; Jean-Marie Saint-Remy

Hemophilia A patients producing antibodies towards FVIII are usually treated with infusions of high doses of FVIII in an attempt to desensitize them. To examine the mechanisms by which such desensitization operates, sequential plasma samples of two unrelated inhibitor patients were analyzed for anti-FVIII and antiidiotypic antibodies before and during infusions of high doses of FVIII. Anti-FVIII antibodies were separated from antiidiotypic antibodies by immunoaffinity chromatography before analysis. We show in the present study that the concentration of anti-FVIII antibodies did not change during a successful desensitization and that antibodies maintained their capacity to inhibit the procoagulant function of FVIII, even though the number of Bethesda units in plasma was reduced to undetectable levels. Using a competition assay with mAbs, we further show that the specificity of human antibodies did not vary significantly during therapy. Finally, we show that the treatment elicited antiidiotypic antibodies, which neutralized the inhibitory capacity of anti-FVIII antibodies. Inhibitor antibodies can therefore not be accurately evaluated in plasma, as their function appears to be neutralized by antiidiotypic antibodies. These findings could have implications for the design of new therapies for hemophilia A patients with inhibitors.


Thrombosis and Haemostasis | 2003

Anti-heavy-chain monoclonal antibodies directed to the acidic regions of the factor VIII molecule inhibit the binding of factor VIII to phospholipids and von Willebrand factor

S Raut; Sylvie Villard; Sabrina Grailly; J G Gilles; Claude Granier; Jean-Marie Saint-Remy; Trevor W. Barrowcliffe

Recent studies have shown that inhibitors develop against acidic regions of the FVIII molecule, which contain important functional sites. However, their mechanisms of inhibition are not well understood. In this study, two anti-human FVIII mouse monoclonal antibodies (MAbs), directed towards the exposed acidic regions of the FVIII molecule, were developed, characterised and their mechanisms of inhibition investigated. The two MAbs, F7B4 and F26F6, had inhibitory titres of 32 and 944 BU/mg respectively, had high affinities for the FVIII molecule (K(D) approximately nM range) and recognised sequences V(357)-F(360) on the acidic a1 region and E(724)-L(731) on the acidic a2 region of the FVIII heavy-chain (HC), respectively. F7B4 inhibited the rate of FXa generation by activated FVIII, whilst both antibodies inhibited FVIII activation by thrombin and blocked thrombin cleavage of FVIII. Furthermore, F7B4 and F26F6 inhibited FVIII binding to (a) phospholipids (IC(50): 77 nM and 40 nM respectively), and (b) VWF (IC(50): 93 nM and 267 nM respectively), despite both having HC specificity. Experiments with F(ab)(2) fragments confirmed the above findings. Taken together these data represent novel findings in that anti-acidic HC antibodies can inhibit FVIII function by a variety of mechanisms, in particular by interfering with the binding of FVIII to phospholipids & VWF.


Blood Coagulation & Fibrinolysis | 1995

Strategy for pre-clinical evaluation of factor VIII concentrates.

J G Gilles; Jean-Marie Saint-Remy

A series of methods and assay systems was designed, using both mouse monoclonal antibodies and purified human polyclonal antibodies, by which alterations in the antigenic properties, and potentially therefore in the immunogenic properties, of FVIII concentrates could be identified. Those methods could be applied to the pre-clinical evaluation of FVIII concentrates. It has become evident that very subtle alterations in FVIII can have dramatic effects on its antigenicity and immunogenicity and it is suggested that an analysis of FVIII preparations, using reagents such as mouse monoclonal antibodies, should be carried out as a pre-clinical evaluation. It is also thought that any haemophiliac patient is at risk of developing anti-FVIII antibodies, even though he had been considered as tolerant to the infusion of FVIII. The diversity of FVIII concentrates now available on the market has multiplied the chances of encountering a product that would give an immune response in some patients and this further stresses the need for a careful check of FVIII concentrates.


Blood | 1993

Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction

J G Gilles; Jozef Arnout; Jozef Vermylen; Jean-Marie Saint-Remy


Thrombosis and Haemostasis | 1993

A higher than expected incidence of factor VIII inhibitors in multitransfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate

Kathelijne Peerlinck; Jozef Arnout; J G Gilles; Jean-Marie Saint-Remy; Jozef Vermylen


Blood | 2000

A human antibody directed to the factor VIII C1 domain inhibits factor VIII cofactor activity and binding to von Willebrand factor

Marc Jacquemin; Abdellah Benhida; Kathelijne Peerlinck; B Desqueper; Luc Vander Elst; Renaud Lavend'homme; R d'Oiron; Rainer Schwaab; Marleen Bakkus; Kris Thielemans; J G Gilles; Jos Vermylen; Jean-Marie Saint-Remy


Blood | 1999

Antifactor VIII Antibody Inhibiting Allogeneic but not Autologous Factor VIII in Patients With Mild Hemophilia A

Kathelijne Peerlinck; Marc Jacquemin; Jozef Arnout; Marc Hoylaerts; J G Gilles; Renaud Lavend'homme; K M Johnson; Kathleen Freson; Dorothea Scandella; Jean-Marie Saint-Remy; Jozef Vermylen


Thrombosis and Haemostasis | 1999

Some Factor VIII (FVIII) Inhibitors Recognise a FVIII Epitope(s) that Is Present only on FVIII-vWF Complexes

J G Gilles; Renaud Lavend'homme; Kathelijne Peerlinck; Marc Jacquemin; Marc Hoylaerts; S Jorieux; C Mazurier; Jozef Vermylen; Jean-Marie Saint-Remy


Archive | 2007

Anti-Idiotypic Antibodies Neutralizing the Inhibitory Activity of an Inhibitory Antibody Directed Against the C1 Domain of Factor VIII

J G Gilles; Marc Jacquemin; Jean-Marie Saint-Remy; Christian Behrens

Collaboration


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Jean-Marie Saint-Remy

Katholieke Universiteit Leuven

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Marc Jacquemin

Katholieke Universiteit Leuven

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Jozef Vermylen

Katholieke Universiteit Leuven

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Kathelijne Peerlinck

United States Military Academy

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Jozef Arnout

Katholieke Universiteit Leuven

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Renaud Lavend'homme

Katholieke Universiteit Leuven

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Abdellah Benhida

Katholieke Universiteit Leuven

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Jos Vermylen

Katholieke Universiteit Leuven

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Kris Thielemans

Vrije Universiteit Brussel

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Luc Vander Elst

Katholieke Universiteit Leuven

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