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Biomedical subjects

L Prin

Publications and source records attributed to L Prin.

At least 55 records · Page 3Linked to original sources

Cerebro-spinal fluid eosinophilia in shunt infections.

Hypereosinophilia has been detected in the CSF of 22 patients in a series of 81 cases of shunt infection. It was related with the evolution of the sepsis. Its persistence at the end of treatment appeared to predict later complications, septic or obstructive, and it could be the sign of latent infection. HE might be the result of a specific reaction directed against the infected material, but a non-specific process cannot be eliminated.

Adolescent↗

Bronchoalveolar lavage in alcoholic liver cirrhosis. T-lymphocyte subsets and immunoglobulin concentrations.

The purpose of this study was to determine the phenotype profiles of immune effector cells and the concentrations of immunoglobulins in the lower respiratory tract of non-smoking patients with alcoholic liver cirrhosis (ALC). Nine nonsmoking patients with liver biopsy-proved ALC (grade B or C cirrhosis in Child's classification), free of clinical pulmonary symptoms, and with normal chest roentgenogram were included in the study. The control group included 12 healthy nonsmokers. Each patient had fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The number of T cells and of lymphocyte subpopulations was determined by immunofluorescence studies using monoclonal antibodies that were specific for CD3, CD4, and CD8 markers. Patients with ALC exhibited a dramatically increased percentage of CD8+ cells in BAL that induced a low CD4/CD8 ratio (0.96 +/- 0.15 vs 1.8 +/- 0.12 in healthy controls). Further characterization of lymphocyte subsets' dual immunofluorescence analysis demonstrated that most of the CD8+ alveolar lymphocytes had a phenotype of cytotoxic cells (CD8+ CD11b-; 48 percent +/- 13 in ALC vs 10 percent +/- 5 in controls). ALC was associated with an appreciable alveolar-capillary "leak" as demonstrated by a significant increase in BAL fluid albumin. In addition, the concentrations of immunoglobulins in BAL fluid were significantly greater in ALC than in controls. However, the relative (to albumin) coefficient of excretion of IgG, A, and M in and alpha 2-macroglobulin BAL fluid was not significantly different between controls and ALC. Our results indicate that increased proportions of CB8+ and especially of CD8+ CD11b- cells are a common feature in the lower respiratory tract of nonsmoking patients with ALC. These changes may be of potential functional importance in the regulation of the local pulmonary immune response in ALC.

Adult↗

The interleukin 2 receptor in the hypereosinophilic syndrome.

The hypereosinophilic syndrome (HES) has been previously described as a clinicobiological entity characterized by a blood eosinophil count of over 1.5 x 10(9)/L of unknown cause associated with several clinical complications. In reality, HES is a heterogeneous group of diseases with variable and unpredictable progress in visceral lesions, thought to be related to the deleterious effects of tissue eosinophil infiltration. Various criteria for discrimination between benign and severe forms of HES have been described. These previous retrospective clinical investigations, using biological and clinical markers, have defined different stages of HES. It appears more relevant, however, to consider elements of disease activity by studying mechanisms of induction of persistent hypereosinophilia. The T-cell dependence of blood eosinophilia has led us to evaluate various markers of T-cell activation in particular. In the present review, we report previous results and perspectives suggested by the study of the interleukin 2 receptor in HES.

Biomarkers↗

Quantification of HTLV-1 proviral copy number in peripheral blood of symptomless carriers from the French West Indies.

The development of human T-cell leukemia type 1 (HTLV-1) diseases are related to an increase in the proviral copy number (VCN) in peripheral blood mononuclear cells (PBMCs). Twenty symptomless anti-HTLV-1-positive blood donors, as well as four symptomatic individuals, all from the French West Indies, were studied. The VCN in PBMCs was determined by quantitative PCR. The VCN values for asymptomatic HTLV-1 carriers (range of less than 100 to approximately 9,500/micrograms of DNA) was nearly always less than the values for symptomatic carriers (range of approximately 5,500 to approximately 29,000/micrograms of DNA). Consequently, the proportion of HTLV-1-infected PBMCs in symptomless and in symptomatic individuals ranged from less than 1/1,500 to approximately 1/16 and approximately 1/27 to approximately 1/5, respectively. No correlation could be found between VCN and age or sex, suggesting the importance of factors other than age and sex as influences on the VCN number.

Adult↗

Elevated serum levels of soluble interleukin-2 receptor: a marker of disease activity in the hypereosinophilic syndrome.

We report here the presence of very high serum levels of the soluble interleukin-2 receptor (sIL-2R) in patients with blood hypereosinophilia with or without detectable markers of malignancy or signs of visceral involvement. The highest sIL-2R levels were observed in 16 eosinophilic patients with T-cell lymphoma (3,440 to 79,500 U/mL). Elevated levels of sIL-2R were also present (1,330 to 22,500 U/mL) in sera from 38 patients with the hypereosinophilic syndrome (HES) without detectable T-cell lymphoma. In this group of patients, the highest levels were noted in the patients with the malignant form of HES. Significantly lower levels were measured in sera of patients with hypereosinophilia associated with parasitic diseases, allergic disorders, or other miscellaneous diseases. Elevated serum sIL-2R levels were not closely paralleled by changes in the number of CD25-positive peripheral blood mononuclear cells as assessed by flow cytometric analysis. However, expression of IL-2R messenger RNA was detected in blood mononuclear cells collected from HES patients. In eight eosinophilic patients with T-cell lymphoma, the serum sIL-2R levels were significantly correlated with the eosinophil counts, and with the total number of blood hypodense eosinophils. alpha-Interferon (alpha-IFN) therapy resulted in both a dramatic clinical improvement and a rapid decrease in sIL-2R levels and blood hypereosinophilia. Similar beneficial effects of alpha-IFN were noted in patients with malignant HES who lacked a detectable T-cell lymphoma. Our data indicate that HES is associated with elevated serum IL-2R levels. The highest levels were observed in the most severe forms of HES with hematologic markers of malignancy or evident visceral involvement. Serum levels of sIL-2R might represent a useful indicator for the management of HES patients. In addition, the respective changes of sIL-2R and blood eosinophilia might reflect distinct processes of mononuclear cell activation affecting the eosinophil lineage.

Adult↗

[Significance of an increase of total IgE].

Under normal condition, serum IgE concentrations are low and controlled by complex regulating mechanisms. Increased IgE synthesis may be associated with a response of IgE antibodies to allergens or parasites. It may also betray a wider disorder in the regulation of IgE production, resulting in a rise of total IgEs of unknown specificity. Broadly speaking, high IgE levels are observed in two main circumstances: allergic ans parasitic diseases. In allergic diseases the diagnostic value of high IhE concentrations is modest, since a search for specific IgEs by cutaneous tests ot laboratory techniques (RAST) is more rewarding than total IgE determination. However, total IgE assays are useful in the detection of atopy in neonates at risk and the identification and therapeutic follow-up of allergic pulmonary aspergillosis. High IgE levels are frequently associated with parasitic diseases, especially helminthiasis. They also reflect a disorder of IgE homeostasis in some types of immunodeficiency, including the classical IgE hyperproduction syndrome. Except for this syndrome, high IgE concentrations merely constitute a secondary diagnostic factor in a wide pathology, but they often bear witness to a subjacent dysregulation of T-cell function.

Adult↗

Human eosinophils from hypereosinophilic patients spontaneously express the p55 but not the p75 interleukin 2 receptor subunit.

The expression of interleukin 2 receptor (IL2R) on eosinophils was investigated in patients with hypereosinophilia. Hypodense activated eosinophils have been described in various diseases such as parasitic or allergic diseases, hypereosinophilic syndrome (HES) associated in some cases to myeloproliferative markers, and more recently described in patients undergoing recombinant IL2 treatment. The presence of p55 alpha chain of IL2R (CD25) on purified eosinophils collected from blood of hypereosinophilic patients was detected by flow cytometry. In 10 out of 19 cases, more than 10% of eosinophils were CD25+. Cross-linking studies on enriched eosinophils showed one 64-75-kDa band, consisting of IL2 (15 kDa) cross-linked to the IL2R p55 subunit. In Northern blot analysis the two messenger mRNA (3.5 and 1.5 kb) encoding the IL2R p55 subunit were identified after hybridization with a CD25 cDNA probe. In contrast, the presence of the IL2R p75 subunit was not detected. These data provide preliminary evidence for the expression of a low-affinity receptor for IL2 on in vivo activated eosinophils and raise the question of the role played by this cytokine in eosinophil differentiation and activation.

Eosinophilia↗

Release of granule proteins by eosinophils from allergic and nonallergic patients with eosinophilia on immunoglobulin-dependent activation.

The release of eosinophil peroxidase (EPO) and eosinophil cationic protein (ECP) was evaluated after incubation of eosinophils (EOSs) from allergic subjects with the specific allergen or with anti-IgE monoclonal antibodies (MAbs). High levels of EPO could be released after addition of the specific allergen (and not unrelated ones) or anti-IgE MAb. Moreover, EPO release with the two stimuli was significantly correlated both in allergic and in nonallergic patients. In the same supernatants, another granule protein, ECP, could not be detected, suggesting a lack of correlation between EPO and ECP release after IgE-dependent stimulation. However, when EOSs with surface-IgA antibodies were incubated with anti-IgA MAb, both EPO and ECP were released. In contrast, incubation of EOSs with anti-IgG MAb induced mainly the release of ECP and not EPO. These results indicate that pharmacologically active mediators can be released by EOSs from allergic and nonallergic patients on immunoglobulin-dependent activation. The results also confirm the hypothesis of a selective release of the various granule proteins and raise the question of transduction signals delivered by the three Fc receptors (Fc epsilon R, FC alpha R, and FC gamma R) present on human EOSs.

Allergens↗

Characterization of a receptor for interleukin 5 on human eosinophils: variable expression and induction by granulocyte/macrophage colony-stimulating factor.

Interleukin 5 (IL-5) acts on eosinophil differentiation and activation, suggesting the existence of a membrane receptor for IL-5 on eosinophils. Here, we report that 125I-labeled recombinant human IL-5 bound, at 4 degrees C, to high affinity receptors on human eosinophils. The association constant was higher for hypodense eosinophils (1.93 x 10(9) M-1) than for normodense cells (0.39 x 10(9) M-1), with a closely related number of receptor sites per cell. No specific binding occurred on neutrophils. The specific binding of IL-5 was induced by overnight incubation at 37 degrees C of human eosinophils with granulocyte/macrophage (GM)-CSF. The levels of increase were significantly higher for normodense than for hypodense eosinophils, suggesting a previous in vivo activation of the later subpopulation by GM-CSF. IL-3 was ineffective by itself but synergistically enhanced the effect of GM-CSF. Specificity studies showed that the binding of 125I-labeled IL-5 was inhibited by IL-5, but not by other cytokines, on human eosinophils. These results show the existence of a specific binding site for IL-5 on human eosinophils with a variable affinity on eosinophil hypodense or normodense subpopulations, as previously reported for other membrane receptors.

Cells, Cultured↗

Presence of antibodies against endothelial cells in the sera of patients with episodic angioedema and hypereosinophilia.

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 less than 0.05 compared with a control group). Serum MBP levels were at 1524, 619 and 1200 pg/ml. All three patients had circulating anti-endothelial cell antibodies, predominantly of the IgG isotype, in contrast to controls (P less than 0.01) or to patients with HES (P less than 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.

Adult↗

Variations in protein expression related to human eosinophil heterogeneity.

In hypereosinophilic patients, eosinophil heterogeneity has been assessed mainly according to morphologic and biologic criteria. In order to investigate the molecular basis of such heterogeneity, biochemical analysis was performed on various eosinophil subpopulations fractionated on metrizamide gradients. Whole cell extracts from purified eosinophils disrupted with a nonionic (NP-40) detergent were successively analyzed by SDS-PAGE and two-dimensional electrophoresis (isoelectric focusing or nonequilibrium pH gradient electrophoresis in the first dimension). Hypodense eosinophils that sediment in the lightest density gradients (18 to 22% metrizamide solution) differed from other purified eosinophils (intermediate and normodense eosinophils respectively collected in 22 to 23% and 23 to 25% metrizamide solutions). Comparative analysis of protein patterns on both monodimensional and bidimensional electrophoresis showed that a basic protein of Mr 51 kDa, present on normodense or intermediate eosinophils, was poorly detected in the case of hypodense eosinophils. In contrast, two other proteins with apparent Mr of about 23 kDa and 41 kDa were exclusively or predominantly identified in these latter cell fractions. Immunochemical analysis with polyclonal antibodies against eosinophil basic proteins and enzymatic assays revealed that the 51-kDa polypeptide could be related to an eosinophil peroxidase-like molecule. In addition, the two proteins detected only in hypodense eosinophils might be related to proteins newly synthesized by in vivo activated eosinophils. Our results suggest that variations in protein expression might represent a good marker of in vivo activation.

Blood Proteins↗