Clin. exp. Immunol. (1990) 82, 38-43
Presence of antibodies against endothelial cells in the sera of patients with episodic angioedema and hypereosinophilia P. LASSALLE, P. GOSSET, V. GRUART, L. PRIN, M. CAPRON, G. LAGRUE*, J.P. KUSNIERZ, A. B. TONNEL & A. CAPRON Centre d'Immunologie et de Biologie Parasitaire, Unite Mixte INSERM U 167, CNRS 624, Institut Pasteur, Lille, and * Service Nephrologie, Hopital Henri Mondor, Creteil, France (Acceptedfor publication 22 May 1990)
SUMMARY We reported three additional cases of a newly described syndrome called episodic angioedema with hypereosinophilia. In order to investigate its pathophysiological mechanisms, four parameters were concurrently investigated, including blood eosinophil density, serum chemoattractant activity, serum major basic protein (MBP) levels and the presence of anti-endothelial cell antibodies. Distribution of eosinophils through a metrizamide density gradient showed a preferential sedimentation of blood eosinophils in intermediate layers, clearly different from the hypodense cells (low-density layers) identified in a group of seven patients with idiopathic hypereosinophilic syndrome (HES). In two of the three patients with cyclic angioedema, a chemotactic activity towards eosinophils was detected in the serum (30 + 6 and 42 + 12 eosinophils per high-power field; P< 0-05 compared with a control group). Serum MBP levels were at 1524, 619 and 1200 pg/ml. All three patients had circulating antiendothelial cell antibodies, predominantly of the IgG isotype, in contrast to controls (P< 0-01) or to patients with HES (P < 0-01). Specificity of the antibody for endothelial cells was demonstrated in the three patients studied by the absence of binding to various blood cells, including monocytes, lymphocytes, eosinophils and platelets. In one case (patient 2), the levels of anti-endothelial cell antibodies, as well as the serum chemoattractant activity to eosinophils varied according to the successive acute phases of the disease. Although further investigations are needed to clarify the exact pathophysiology of this syndrome, and especially the possible participation of the anti-endothelial cell antibodies in the cutaneous lesions, these data suggest that angioedema observed in this syndrome could result from the combined effects of activated eosinophils and of immunologically induced endothelial lesions. Keywords endothelial cells autoantibodies eosinophilia Here we report three additional cases, observed in two 19year-old young men and a 48-year-old woman who all exhibited clinical and biological features consistent with the syndrome described by Gleich et al. (1984). Our interest was focused on the presence of circulating IgG antibodies specifically directed against endothelial cells. These anti-endothelial cell antibodies may be involved in the generation of altered vascular permeability and participate, together with eosinophils, to the pathogenesis of angioedema.
INTRODUCTION Gleich et al. (1984) described a new, relatively benign syndrome consisting of episodic angioedema, hypereosinophilia, elevated IgM levels, and variable hypocomplementaemia. Although the aetiology is still obscure, current concepts of pathogenesis support a major role for eosinophils. Symptoms appear to be related to high peripheral blood eosinophil counts. Histologic studies of the dermis show the presefce of degranulated mast cells, diffuse eosinophilic and perivascular lymphocytic infiltration, and major basic protein (MBP) deposition (Gleich et al., 1984). This clinical entity may be distinguished from the idiopathic hypereosinophilic syndrome described by Chusid et al. (1975), because of its good prognosis and rapid response to corticosteroid therapy.
CASE REPORTS Patient 1 In June 1978, this 10-year-old boy presented the first recurrent episode of swelling of his face associated with eosinophilia; these symptoms occurred monthly and remained well tolerated. Evaluation at this time failed to find any evidence of collagen vascular disease, cardiac and neurologic involvement, or para-
Correspondence: Dr P. Lassalle, Centre d'Immunologie et de Biologie Parasitaire, Unite Mixte INSERM U 167, CNRS 624, Institut Pasteur, 1, rue du Pr. A. Calmette, 59019 Lille Cedex, France.
38
Anti-endothelial cell antibodies in episodic angioedema and hypereosinophilia
39
Table 1. Laboratory data of the three patients with episodic angioedema and
hypereosinophilia
Leucocytes (103/ml) Neutrophils Eosinophils Lymphocytes Monocytes IgG (g/l) IgA (g/l) ,gM (g//) IgE (IU/ml) Immune complexes (g//) Rheumatoid factor (IU/ml) MBP (pg/ml)*
Patient 1
Patient 2
Patient 3
16400 1400 12400 2300 300 16-3 1.1 13 7 754 5
Presence of antibodies against endothelial cells in the sera of patients with episodic angioedema and hypereosinophilia P. LASSALLE, P. GOSSET, V. GRUART, L. PRIN, M. CAPRON, G. LAGRUE*, J.P. KUSNIERZ, A. B. TONNEL & A. CAPRON Centre d'Immunologie et de Biologie Parasitaire, Unite Mixte INSERM U 167, CNRS 624, Institut Pasteur, Lille, and * Service Nephrologie, Hopital Henri Mondor, Creteil, France (Acceptedfor publication 22 May 1990)
SUMMARY We reported three additional cases of a newly described syndrome called episodic angioedema with hypereosinophilia. In order to investigate its pathophysiological mechanisms, four parameters were concurrently investigated, including blood eosinophil density, serum chemoattractant activity, serum major basic protein (MBP) levels and the presence of anti-endothelial cell antibodies. Distribution of eosinophils through a metrizamide density gradient showed a preferential sedimentation of blood eosinophils in intermediate layers, clearly different from the hypodense cells (low-density layers) identified in a group of seven patients with idiopathic hypereosinophilic syndrome (HES). In two of the three patients with cyclic angioedema, a chemotactic activity towards eosinophils was detected in the serum (30 + 6 and 42 + 12 eosinophils per high-power field; P< 0-05 compared with a control group). Serum MBP levels were at 1524, 619 and 1200 pg/ml. All three patients had circulating antiendothelial cell antibodies, predominantly of the IgG isotype, in contrast to controls (P< 0-01) or to patients with HES (P < 0-01). Specificity of the antibody for endothelial cells was demonstrated in the three patients studied by the absence of binding to various blood cells, including monocytes, lymphocytes, eosinophils and platelets. In one case (patient 2), the levels of anti-endothelial cell antibodies, as well as the serum chemoattractant activity to eosinophils varied according to the successive acute phases of the disease. Although further investigations are needed to clarify the exact pathophysiology of this syndrome, and especially the possible participation of the anti-endothelial cell antibodies in the cutaneous lesions, these data suggest that angioedema observed in this syndrome could result from the combined effects of activated eosinophils and of immunologically induced endothelial lesions. Keywords endothelial cells autoantibodies eosinophilia Here we report three additional cases, observed in two 19year-old young men and a 48-year-old woman who all exhibited clinical and biological features consistent with the syndrome described by Gleich et al. (1984). Our interest was focused on the presence of circulating IgG antibodies specifically directed against endothelial cells. These anti-endothelial cell antibodies may be involved in the generation of altered vascular permeability and participate, together with eosinophils, to the pathogenesis of angioedema.
INTRODUCTION Gleich et al. (1984) described a new, relatively benign syndrome consisting of episodic angioedema, hypereosinophilia, elevated IgM levels, and variable hypocomplementaemia. Although the aetiology is still obscure, current concepts of pathogenesis support a major role for eosinophils. Symptoms appear to be related to high peripheral blood eosinophil counts. Histologic studies of the dermis show the presefce of degranulated mast cells, diffuse eosinophilic and perivascular lymphocytic infiltration, and major basic protein (MBP) deposition (Gleich et al., 1984). This clinical entity may be distinguished from the idiopathic hypereosinophilic syndrome described by Chusid et al. (1975), because of its good prognosis and rapid response to corticosteroid therapy.
CASE REPORTS Patient 1 In June 1978, this 10-year-old boy presented the first recurrent episode of swelling of his face associated with eosinophilia; these symptoms occurred monthly and remained well tolerated. Evaluation at this time failed to find any evidence of collagen vascular disease, cardiac and neurologic involvement, or para-
Correspondence: Dr P. Lassalle, Centre d'Immunologie et de Biologie Parasitaire, Unite Mixte INSERM U 167, CNRS 624, Institut Pasteur, 1, rue du Pr. A. Calmette, 59019 Lille Cedex, France.
38
Anti-endothelial cell antibodies in episodic angioedema and hypereosinophilia
39
Table 1. Laboratory data of the three patients with episodic angioedema and
hypereosinophilia
Leucocytes (103/ml) Neutrophils Eosinophils Lymphocytes Monocytes IgG (g/l) IgA (g/l) ,gM (g//) IgE (IU/ml) Immune complexes (g//) Rheumatoid factor (IU/ml) MBP (pg/ml)*
Patient 1
Patient 2
Patient 3
16400 1400 12400 2300 300 16-3 1.1 13 7 754 5
