The binding of some human antiendothelial cell antibodies induces endothelial cell apoptosis.

Bordron, Anne; Dueymes, Maryvonne; Levy, Yair; Jamin, Christophe; Leroy, J P; Piette, Jean‐Charles; Shoenfeld, Yehuda; Youinou, Pierre

doi:10.1172/jci2261

Cited by 202 publications

(135 citation statements)

References 24 publications

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“…For experiments with inhibitors, cells were preincubated with 1 g/ml wortmannin (Sigma-Aldrich) or 1 M bisindolylmaleimide (Calbiochem) in RPMI 1640 medium at 37°C for 1 h before stimulation. Anti--induced apoptosis was confirmed using three other assays that we have described previously in great detail (16,17,41,42): examination of nuclear condensation, measurement of hypoploidy, and DNA fragmentation analysis.…”

Section: Measurement Of Apoptosismentioning

confidence: 56%

B Cell Response to Surface IgM Cross-Linking Identifies Different Prognostic Groups of B-Chronic Lymphocytic Leukemia Patients

Nédellec¹,

Renaudineau²,

Bordron³

et al. 2005

The Journal of Immunology

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On the basis of responses to surface IgM (sIgM) cross-linking, B cells from 41 patients with B-chronic lymphocytic leukemia were categorized as 15 nonresponders (group I) and 26 responders (group II). The latter cases were subclassified as those seven where proliferation was induced (subgroup IIa) and the remaining 19 in whom apoptosis occurred (subgroup IIa). Signal disruption in group I was confirmed by the absence of Ca2+ mobilization. Activation of PI3K was constitutive in subgroup IIa, but not in subgroup IIb, and that of Akt induced by anti-μ in subgroup IIa, but not in subgroup IIb. Among the MAPK, ERK was more highly activated relative to p38 in subgroup IIa, whereas activation of p38 predominated over that of ERK in subgroup IIb. For subgroup IIb cells, based on tyrosine phosphorylation and translocation into lipid rafts, sIgM signaling was shown to be enhanced by Zap70. The different consequences of signaling through sIgM were associated with biological prognosis indicators. These included high levels of CD38, lack of mutations in the IgVH chain genes, preferential usage of full-length CD79b, and severe clinical stage. Thus, modification of sIgM-induced signaling could be a therapeutic approach.

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Section: Measurement Of Apoptosismentioning

confidence: 56%

B Cell Response to Surface IgM Cross-Linking Identifies Different Prognostic Groups of B-Chronic Lymphocytic Leukemia Patients

Nédellec¹,

Renaudineau²,

Bordron³

et al. 2005

The Journal of Immunology

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“…22,23 Similarly, antifibroblast antibodies, detected in up to 30% of patients with SSc-PAH, 24 activate several mechanisms central to the vascular remodeling process, including the activation of platelet-derived growth factor receptors, which stimulate the release of reactive oxygen species, fi broblast proliferation, and collagen synthesis. 18,25 In many autoimmune-mediated diseases (ie, systemic lupus erythematosus, mixed connective tissue disease [CTD]), PAH improves with aggressive immunosuppression.…”

Section: Autoimmune Dysfunctionmentioning

confidence: 99%

Systemic Sclerosis-associated Pulmonary Arterial Hypertension

Pavec

Humbert

Mouthon

et al. 2010

Am J Respir Crit Care Med

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Systemic sclerosis (SSc) is a complex, multisystem disease characterized by fi brosis and excessive collagen deposition within the skin and internal organs, chronic infl ammation, autoimmune dysregulation, and microvascular endothelial dysfunction. There are two forms of SSc that are characterized by the extent of skin involvement. Limited cutaneous SSc predominantly involves the skin of the hands, arms, and face, and diffuse SSc involves large areas of skin and multiple organs. 1 Both forms are systemic diseases associated with signifi cant morbidity and mortality. Historically, mortality was largely caused by renal disease. With the advent of angiotensin-converting enzyme inhibitors to treat SSc renal crisis, SSc-associated pulmonary arterial hypertension (SSc-PAH) has emerged as a leading cause of morbidity and mortality, accounting for up to 30% of premature deaths. 2 Although SSc-PAH represents a signifi cant proportion of the pulmonary arterial hypertension (PAH) population (15%-30%), 3,4 much of what we know about PAH is derived from studies of idiopathic PAH (IPAH).Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc ) and affects up to 12% of all patients with SSc, with a 50% mortality rate within 3 years of PAH diagnosis. Compared with the idiopathic form of PAH (IPAH), patients with SSc-associated PAH (SSc-PAH) have a threefold increased risk of death and may receive a diagnosis late in the course of disease because of insidious onset and the high prevalence of cardiac, musculoskeletal, and pulmonary parenchymal comorbidities. Treatment with conventional forms of PAH therapy often yield poor results compared with IPAH cohorts; unfortunately, the exact reasons behind this remain poorly understood but likely include variations in the pathologic mechanisms, differences in cardiovascular response to increasing afterload, and inadequate strategies to detect and treat SSc-PAH early in its course. Current methods for screening and longitudinal evaluation of SSc-PAH, such as the 6-min walk test, transthoracic echocardiography, and MRI, each have notable advantages and disadvantages. We provide an up-to-date, focused review of SSc-PAH and how it differs from IPAH, including pathogenesis, appropriate screening for disease onset, and new approaches to treatment and longitudinal assessment of this disease. CHEST 2013; 144(4):1346-1356Abbreviations: 6MWD 5 6-min walk distance; CCB 5 calcium channel blocker; CTD 5 connective tissue disease; D lco 5 diffusing capacity of lung for carbon monoxide; EIPAH 5 exercise-induced pulmonary arterial hypertension; ERA 5 endothelin receptor antagonist; FC 5 functional class; ILD 5 interstitial lung disease; IPAH 5 idiopathic pulmonary arterial hypertension; LV 5 left ventricular; mPAP 5 mean pulmonary artery pressure; PAH 5 pulmonary arterial hypertension; PASP 5 pulmonary artery systolic pressure; PDE-5I 5 phosphodiesterase type 5 inhibitor; PFT 5 pulmonary function test; PH 5 pulmonary hypertension; pro-BNP 5 pro-brain natriuretic pe...

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“…They represent a heterogeneous group of antibodies directed against a variety of antigenic determinants on ECs. In the setting of autoimmune diseases, antibodies to EC have been shown to induce both up-regulation of adhesion molecules with consequent mononuclear cell adhesion and EC apoptosis (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Bas‐Bernardet

Hourmant

Coupel

et al. 2003

American Journal of Transplantation

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The vascular endothelium of transplanted organs represents an important target for allograft-directed immune responses. Although HLA antigens expressed on graft endothelial cells (EC) can become targets of the host immune response, the role of other, non-HLA-encoded EC antigens has been proposed but is still unclear. The aim of this study was to investigate the presence of and to characterize anti-EC antibodies (AECA) in 57 kidney transplant recipients according to their HLAimmunization status. Flow cytometry in pretransplant sera was used to detect AECA reactive with surface antigens on ABO and HLA-typed primary cultures of arterial ECs, stimulated or not with tumor necrosis factor-a (TNFa) or interferon-g (IFNg). FACS analysis revealed the presence of AECA in 47% of HLA-sensitized (PRA = 10%: mostly IgG) vs. 16.0% in nonsensitized patients (PRA < 10%) (p < 0.02). No significant correlation was found between the presence of AECA and acute rejection occurrence and graft outcome. Non-HLA reactive AECA are directed against TNFa-and IFNg-inducible membrane molecule(s), and react with two predominant antigens of~35 kDa and~50 kDa expressed on ECs but not on B cells. Binding of AECA decreases in vitro EC viability by 50-60% by promoting EC apoptosis, as demonstrated by DNA fragmentation assays.

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The binding of some human antiendothelial cell antibodies induces endothelial cell apoptosis.

Cited by 202 publications

References 24 publications

B Cell Response to Surface IgM Cross-Linking Identifies Different Prognostic Groups of B-Chronic Lymphocytic Leukemia Patients

B Cell Response to Surface IgM Cross-Linking Identifies Different Prognostic Groups of B-Chronic Lymphocytic Leukemia Patients

Systemic Sclerosis-associated Pulmonary Arterial Hypertension

Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

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