Anti-endothelial Cell Antibodies In Patients Research Articles

Detection of anti-endothelial cell antibodies in patients with connective tissue diseases by flow cytometry and their relation to endothelial cell activation.

Antiendothelial cell antibodies (AECA) have been detected by flow cytometry analysis in 23 out of 80 patients with connective tissue diseases. Ten out of 19 serum samples from patients with systemic lupus erythematosus (SLE) were positive. These antibodies were not detectable in healthy donors. We examined the capacity of serum samples to induce endothelial cell activation by modulating cell adhesion molecule expression on human umbilical vein endothelial cells. We found that sera from both AECA-positive and AECA-negative patient groups induced a significantly higher expression of E-selectin compared to healthy controls (P<0.05). There were no differences in the ICAM-1 on VCAM-1 expression. Our data suggest that increased E-selectin expression in activated endothelium in patients with various connective tissue disorders is not related to the production of AECA.

Clinical associations of anti-endothelial cell antibodies in patients with systemic lupus erythematosus.

The aim of this study was to define the clinical associations of anti-endothelial cell antibody (AECA) in systemic lupus erythematosus (SLE) patients by measuring serum AECA titers to correlate with the disease activity and clinical manifestations. Forty-one SLE patients and 27 controls were studied. Serum samples were collected at the time of patient presentation with disease exacerbation and 4 weeks after the start of treatment. The disease activity was evaluated by the SLE Disease Activity Index (SLEDAI). AECA was detected by enzyme-linked immunosorbent assay (ELISA) methods with the surface antigen of the immortalized human microvascular endothelial cell line (HMEC-1). The mean immunoglobulin (Ig)G-AECA and IgM-AECA optical densities (ODs) were significantly higher in patients with SLE compared with controls [mean +/- standard deviation (SD), 0.32 +/- 0.15 vs 0.18 +/- 0.16 and 0.29 +/- 0.14 vs 0.21 +/- 0.09, respectively]. There was a positive correlation between IgG-AECA and the SLEDAI scores. The positivity rate of AECA in the groups with digital vasculitis, neuropsychiatric lupus, and anti-cardiolipin antibody was significant. In conclusion, AECA may be involved in the pathogenesis of SLE and was correlated with the disease activity. It was also associated with clinical manifestations such as digital vasculitis, neuropsychiatric lupus, and anti-cardiolipin antibody positivity.

Anti-endothelial cell antibodies in patients with coronary atherosclerosis

Anti-endothelial cell antibodies (AECA) have been shown to possess endothelial cell activation properties and to harbor pathogenic potential in experimental animal models of autoimmune systemic disorders. Atherosclerosis is a form of an inflammatory condition in which the immune system has been shown to be involved. The aim of the present study was to assess the presence of AECA in patients with coronary atherosclerosis. A total of 134 patients admitted for chest pain of suspected anginal origin were evaluated for coronary artery atherosclerosis by angiography. Sera were drawn prior to the procedure for the determination of AECA employing cyto-ELISA. AECA positive sera were further evaluated for its ability to promote in vitro E-selectin expression by HUVEC using a cell-based ELISA. Patients with no coronary artery involvement had levels of AECA that did not differ from those obtained for patients with confirmed coronary atherosclerosis (one, two or three vessel disease). Furthermore, AECA positive sera from patients, with or without coronary atherosclerosis displayed similar capacity of inducing E-selectin expression by endothelial cells. AECA may not stand as an optimal mean of discriminating atherosclerotic from non-atherosclerotic patients. The ability of AECA to activate endothelial cells is also not unique to patients with atherosclerosis and is evident also in age-matched control subjects.

Identification of anti-endothelial cell antibodies in patients with chronic anal fissure

Identification of anti-endothelial cell antibodies in patients with chronic anal fissure

Identification of anti-endothelial cell antibodies in patients with chronic anal fissure

Recent studies demonstrate that chronic anal fissure can be the consequence of a local ischemic process. Thus hypothesizing that at the perianal level the interaction of immune component with endothelium could constitute a mechanism determining ischemia and hypertonia, the presence or absence of circulating anti-endothelial cell antibodies (AECAs) was determined in the serum of patients with anal fissure. The study was carried out on 30 patients: 10 with posterior chronic anal fissure (group 1), 10 with grades III and IV hemorrhoids (group 2), and 10 without previous or active anorectal disease, or both (group 3). An indirect immunofluorescence assay on sections of rat kidney tissue was used to identify AECA in the peripheral blood. The assay result was positive for AECAs in 12 patients, all with anorectal disease when compared to the control group (P = .001). The basal anal tone was higher in the AECA-positive patients than in the AECA-negative patients (P = .001). Only the patients with anal fissure or hemorrhoids were AECA positive. All healthy controls tested negative for AECA. Although the number of subjects studied is small, the presence of auto-antibodies directed against the endothelial cells in the serum of these patients supports the hypothesis that the endothelium is involved in the anal disease.

Anti-endothelial cell IgG antibodies from patients with Wegener's granulomatosis bind to human endothelial cells in vitro and induce adhesion molecule expression and cytokine secretion.

To elucidate the role of anti-endothelial cell antibodies (AECA) in vascular inflammation in patients with Wegener's granulomatosis (WG). IgG fractions from 3 AECA-positive WG patients, IgG from 3 AECA-negative WG patients, and IgG from healthy donors were tested for their ability to: a) bind to endothelial cells and to display complement-dependent or antibody-dependent cellular cytotoxicity, b) modulate cell membrane expression of adhesion molecules, as evaluated by cytofluorometry and by immunoenzymatic assay, and c) induce the secretion of interleukin-1 beta (IL-1 beta), IL-6, IL-8, and monocyte chemotactic protein 1 (MCP-1). We found that AECA IgG from WG patients do not display any significant cytotoxicity but are able to up-regulate the expression of E-selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 and to induce the secretion of IL-1 beta, IL-6, IL-8, and MCP-1. AECA in patients with WG could play a potential pathogenetic role by activating endothelial cells, and thus facilitating leukocyte recruitment and adhesion to endothelial surfaces, rather than by displaying a cytotoxic activity.

Prevalence of anti-endothelial cell antibodies in patients with Sneddon's syndrome

Background : Sneddon's syndrome consists of widespread livedo reticularis and ischemic cerebral manifestations. Its pathogenesis remains unclear. Endothelial cells could be the primary target tissue. Objective : Our aim was to determine the prevalence of anti-endothelial cell antibodies (AECA) in a large series of patients with Sneddon's syndrome. The results were compared with those of three groups of control subjects: 39 patients with active periarteritis nodosa, 20 patients hospitalized for stroke without livedo, and 28 healthy persons. Methods : AECA were detected with enzyme-linked immunosorbent assay with hybrid cells (EA.hy926) before and after absorption on epithelial cells ( A 549 8 ) to avoid false positivity from antibodies reacting with membranous epithelial antigens. Results : Twenty-two patients with Sneddon's syndrome had AECA (35%). Of the control subjects, 11 patients with active periarteritis nodosa (28%), 1 of 20 patients with a recent stroke without livedo, and no healthy persons had AECA. Conclusion : AECA were frequently found in patients with Sneddon's syndrome, in contrast to the patients with stroke without livedo. The clinical significance and involvement of these antibodies in the pathogenesis of endothelial lesions in Sneddon's syndrome remain to be ascertained.

Lupus nephritis.

Lupus nephritis is a major cause of morbidity and mortality arising from systemic lupus erythematosus. The pathology seen on renal biopsy and clinical features of renal involvement remain major prognostic factors and therapeutic guides. Serologic markers also correlate with disease activity, but more significantly, the identification of cationic and anti-endothelial cell antibodies in patients may have pathogenetic implications. Experimental studies demonstrating pathogenic roles for cationic nuclear antigens, cationic and anti-idiotypic antibodies, and genetic control of antibody production, are being transferred to the clinic. Duplication of these results in patients suggests that similar mechanisms are operative in humans. Insights gained from pathological studies will lead to new therapeutic strategies, but at present lupus nephritis therapy is based on nonspecific immunosuppression. Therapeutic trials testing several established and new modalities have been published in the past year, but they are anecdotal and lacking in controls.

Prevalence of anti-endothelial cell antibodies in patients with autoimmune diseases.

The prevalence of anti-endothelial cell antibodies (AECA) of IgA, IgG and IgM classes was studied by means of enzyme-linked immunosorbent assays (ELISA) in 466 patients with autoimmune/inflammatory disorders. The reference limits in the ELISAs for the AECA were determined from a random population sample of 249 subjects. The frequency of AECA was highest in patients with SLE (n = 42), 14.6% mainly of IgG class, and the presence of AECA correlated with disease activity in these patients. In the RA patient group (n = 200), 9.5% had AECA, mostly of IgA type. We found no association between the presence of AECA and extra-articular manifestations of RA or survival rate. In patients with undefined connective tissue disease (n = 57), ankylosing spondylitis (n = 109), and psoriatic arthritis (n = 58), the frequency of AECA corresponded to that of the random population sample. In a cohort of samples sent to the laboratory for determination of anti-nuclear antibodies (ANA) there was a correlation between the presence of ANA and AECA. Our findings indicate that RA patients are characterized by IgA class AECA, whereas SLE patients have IgG class AECA also correlating to disease activity.

Antiendothelial Cell Antibodies in Patients with the Antiphospholipid Syndrome

Antiendothelial cell antibodies (AECA) have been detected in 20 out of 30 patients (67%) with thrombosis associated with antiphospholipid antibodies. Seven patients had systemic lupus erythematosus and 13 had the "primary" antiphospholipid syndrome. Seven patients had both IgG and IgM AECA, 9 had IgG AECA only, and 4 had only IgM AECA. None of 30 control patients with thrombotic events not related to antiphospholipid antibodies had a positive titre of AECA (P less than 0.001). No correlation between AECA, antinuclear antibodies, anti-dsDNA antibodies, anti-neutrophil cytoplasm antibodies, precipitating antibodies to soluble nuclear and cytoplasmic antigens or complement components was found. The possible role of these AECA in the pathogenesis of thrombotic events is discussed.

IgG and IgM anti-endothelial cell antibodies in patients with collagen-vascular disorders

A cellular enzyme-linked immunosorbent assay (ELISA) was used to detect circulating anti-endothelial cell antibodies (AECA) in sera of patients suffering from rheumatoid arthritis (RA). Felty's syndrome (FS), systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS) and those with a "lupus anticoagulant" (LA). IgG AECA were detected in RA, FS, SLE and LA sera, while IgM AECA were only detected in RA and FS. AECA were not specific for endothelial cells. However, IgG binding to endothelial cells and dermal fibroblasts was F(ab) mediated while in all other cell types tested, nonspecific binding most likely via the Fc region occurred. In RA and FS rheumatoid factor was shown to augment immunoglobulin binding to endothelial cells. Additional studies revealed that some of these pathological sera also contained cytotoxic IgG autoantibodies which fixed complement and damaged human umbilical vein endothelial cells in vitro. These studies suggest that a group of autoantibodies, present in a variety of collagen vascular disorders, react with endothelial cells and thus may be important aetiopathogenic factors in the vasculopathies associated with these disorders.