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Biomedical subjects

I J Ansotegui

Publications and source records attributed to I J Ansotegui.

At least 19 recordsLinked to original sources

Continuing Medical Education: an international reality.

We are all aware today of the growing interest in continuing medical education (CME) programmes in many European Countries and it is important to understand why and how CME could become an international reality. It is obvious that patients need a good doctor--the best possible--as far as medical knowledge, attention to the patient's quality of life and cost-control is concerned. All European health care systems have to take into consideration everything that causes patient dissatisfaction, risk management and unjustified expenses. An example is the increase of claims and complaints against doctors and the strong attention of patients to medical procedures. In other words, medicine worldwide is becoming a service industry and has to consider quality and quantity of performances as well as to pay attention to personal responsibility. The object of our work is to evaluate the CME systems present in Europe, to show the work done on CME by the CME Committee of the European Academy of Allergology and Clinical Immunology and to highlight the Consensus Report on CME approved by an international panel of CME experts.

Clinical Competence↗

Cross-reactivity between obeche wood (Triplochiton scleroxylon) and natural rubber latex.

BACKGROUND: Several studies have shown that allergy to natural rubber latex is associated with cross reactivity to other plants. We have investigated a possible cross reactivity with a tree belonging to the Sterculiaceae family, Tryplochiton scleroxylon, in a patient allergic to obeche wood, that began to suffer symptoms of allergy in contact with latex. METHODS: Determinations of specific IgE by CAP to obeche, natural rubber latex (NRL) and recombinant allergens of latex were done. Immunoblotting was performed to study allergens detected by serum of our patient. CAP-inhibition methods were used to study cross-reactive between NRL and obeche wood. RESULTS: In obeche extract, 4 bands were found of an apparent molecular weight of 18, 38, 75 and 199 kDa. In NRL extract the allergens have a molecular weight around 18, 21, 32, 38, 60, 70 and 199 kDa. IgE to latex was almost completely inhibited (96%) by the obeche extract in CAP-inhibition studies. Using obeche extract as inhibitor, IgE binding to native hevein (nHevb 6.02) was reduced by 25%. CONCLUSIONS: The results obtained in CAP-inhibition demonstrate the existence of cross-reactivity between proteins in NRL and obeche wood. In our patient, a band of apparent molecular weight of 38 kDa could be the most important allergen.

Adult↗

Allergy to dermatophagoides in a group of Spanish gypsies: genetic restrictions.

BACKGROUND: Spanish gypsies have traditionally lived as nomads, a reason why few epidemiological studies were done in this ethnic group. However, the high prevalence of asthmatic diseases demonstrated in a population residing in the North of Spain induces us to analyse whether it was due to the influence of genetic loci previously implicated in other population studies as causing the disorders. METHODS: DRB1* and DQB1* HLA class II, TCR-Valpha8.1, FcepsilonRI-beta Rsa I exon 7 and intron 2, TNF-beta (LTalpha-Nco I) and CD14, were tested for association with asthma and atopy by multiple regression analysis, in 5 families comprising 87 individuals. RESULTS: Significant associations were found with DQB1*02 (p = 0.02) and DQB1*0301 (p = 0.008) and elevated levels of total serum IgE. A negative association (p = 0.02) was found between total serum IgE and DRB1*14. FcepsilonRI-beta Rsa I-In2 allele 1 was associated with high levels of total serum IgE (p = 0.04). Levels of Der p 1 IgE antibodies were negatively associated with DRB1*11-DQB1*0301 (p = 0.007), and positively with TCR Valpha-8 allele 1 (p = 0.04) and with FcepsilonRI-beta Rsa I-In2 allele 1 (p = 0.009). CONCLUSIONS: Our results do not show any association between asthma and the genetic loci studied although they do suggest the existence of multiple genetic influences on the allergic response in these families.

Adult↗

Specific IgE antibodies in the diagnosis of atopic disease. Clinical evaluation of a new in vitro test system, UniCAP, in six European allergy clinics.

A new immunoassay system utilizing new automatic instrumentation, new software for evaluation of data, and reagents updated for increased speed and accuracy was evaluated. Six clinical studies included 894 consecutive patients. Major symptoms were rhinoconjunctivitis, asthma, atopic dermatitis, and urticaria. The prevalence of inhalant allergy was 54-69%. Phadiatop, detecting atopic sensitization to common inhalant allergens, agreed with clinical diagnosis in 764/836 cases (91.4%). The clinical sensitivity and specificity were 93% and 89%, respectively. The clinical sensitivity and specificity of UniCAP specific IgE derived from 5170 comparisons with clinical diagnosis were 89% and 91%, respectively. Specific IgE measurements in UniCAP and in the Pharmacia CAP System agreed in 266/274 cases (97%). A comparison of the sensitivity and specificity of Pharmacia CAP System RAST in 1987 and with UniCAP specific IgE in 1995 showed equivalent performance without change of efficacy or degradation of IgE antibodies after 8 years. The systems were equivalent also in terms of measured values (r=0.96, slope=1.12), confirming the standardization of allergens and of assay calibration. UniCAP is an efficient laboratory system for routine diagnostic testing of allergy and a valuable tool for basic studies on allergens and antibodies.

Administration, Inhalation↗

Posttranslational regulation of Lck and a p36-38 protein by activators of protein kinase C: differential effects of the tumor promoter, PMA, and the non-tumor-promoter, bryostatin.

T cell activation via the antigen receptor or by PKC-activating drugs results in phosphorylation of Lck and alteration of its electrophoretic mobility. Although tyrosine phosphorylation appears to regulate Lck enzymatic activity, the significance of phosphorylation of serine residues and its relevance to the cell proliferation process are yet unclear. We found that the PKC activator, bryostatin, like PMA, induced the conversion of p56lck to a slower migrating form with an apparent molecular mass of 60 kDa. The effect of PMA lasted over 48 hr but that of bryostatin was transient and correlated in time kinetics with that of the bryostatin-induced degradation of PKC. The effects of bryostatin were dominant over those of PMA. In addition, PKC was found to affect both serine and tyrosine phosphorylation of Lck but had no significant effect on the in vitro catalytic activity of Lck. To test whether serine phosphorylation of Lck may affect its ability to bind tyrosine phosphoproteins, we compared Lck immunoprecipitates from PMA- and bryostatin-treated T cells. We found that a 36- to 38-kDa tyrosine phosphoprotein co-immunoprecipitated with Lck from cells that were treated for 24 hr with PMA, but not bryostatin. A p36-38 from PMA- but not bryostatin-treated cells also interacted with an Lck-SH2 fusion protein, suggesting differential regulation of p36-38 by PMA and bryostatin. Furthermore, in vitro phosphorylation of p36-38 occurred in lysates of cells that were treated for 24 hr with PMA, but not in lysates of bryostatin-treated cells. The results show that tyrosine phosphorylation and the association of p36-38 with Lck are differentially affected by bryostatin and PMA and suggest that PKC regulates the interaction of potential signaling molecules with Lck, thereby regulating biochemical events that are relevant to T cell mitogenesis and/or transformation.

Adjuvants, Immunologic↗

The use of IgE immunoblotting as a diagnostic tool in Anisakis simplex allergy.

BACKGROUND: The fish parasite Anisakis simplex is the etiologic agent of anisakiasis and induces IgE-mediated reactions. Skin prick tests (SPTs) and the measurement of specific IgE to A. simplex were, in our experience, not valid tools with which to discriminate between allergic and nonallergic patients because many control subjects also had positive results. OBJECTIVE: The study was carried out to assess the usefulness of IgE immunoblotting in the diagnosis of allergy to A. simplex. METHODS: We have studied 61 patients with acute symptoms of urticaria, angioedema, or anaphylaxis and positive specific IgE to A. simplex. According to the anamnesis, time interval between ingestion of fish and clinical onset of symptoms, and exclusion of other causes of allergy, three different groups of patients were established: group A (allergic), group NA (non-allergic), and group D (doubtful). Fifty-one healthy donors were included as control subjects (group C). IgE immunoblotting with A. simplex whole-body extract was performed in all patients and control subjects. RESULTS: Four patterns of immunoblotting were observed: type 1, with a group of several bands of medium molecular weight and others of low molecular weight; type 2, two or more bands of medium molecular weight; type 3, only one band of medium molecular weight; type 4, without any band. There was a significant predominance of blotting type 1 in group A and type 4 in group C. CONCLUSION: These data suggest that IgE immunoblotting is the most useful approach to A. simplex allergy diagnosis.

Acute Disease↗

IL-10 production and CD40L expression in patients with common variable immunodeficiency.

The authors studied CD40 ligant (CD40L) expression and interleukin-10 (IL-10) production in 16 patients with common variable immunodeficiency (CVI). Mean CD40L expression, determined by using cytofluorimetry, and measured as the mean fluorescence intensity following stimulation of peripheral blood mononuclear cells (PBMC) with phorbol myristate acetate (PMA) and calcium ionophore in 12 patients, was comparable to that of controls. However, three CVI patients showed fluorescence intensity in stimulated cells below 2 standard deviations of normal donors' mean and two other patients had only a slight increase of stimulated versus unstimulated cells (< 10 channels). IL-10 production after stimulation of PBMC with both anti-CD3 or anti-CD3 plus PMA gave similar results in CVI patients and normal controls. In vitro stimulation of PBMC with anti-CD40 and various combinations of cytokines (IL-2, IL-4 and IL-10) induced IgG production above 100 ng/ml in one CVI patient out of 13 tested. The data suggest that alterations of IL-10 production are unlikely to play a major role in the pathogenesis of impaired IgG production in most CVI patients. CD40L appears to be normally expressed in two thirds of CVI patients, but it may be functionally defective.

Adolescent↗

Anisakis simplex, a relevant etiologic factor in acute urticaria.

Anisakis simplex, a parasite of fish and cephalopods, can induce IgE-mediated reactions. This study aimed to determine the etiologic role of A. simplex in patients affected by urticaria/angioedema (AE) or anaphylaxis. We studied 100 adult subjects suffering acute episodes of urticaria/AE, by anamnesis, prick tests with A. simplex and fish-mix extracts, and total and specific IgE to both A. simplex and cod. The following criteria of A. simplex allergy were considered: 1) urticaria/AE within 6 h after fish ingestion; 2) specific IgE to A. simplex; 3) positive prick test to A. simplex extract; 4) exclusion of other suspected causes. Double-blind, placebo-controlled food challenge was not carried out because ethical considerations forbid challenge with a parasite. Specific IgE to A. simplex (> 0.7 kU/l) was found in 22 subjects, but only eight were diagnosed as having A. simplex allergy. Other allergens were involved in 37 patients, and 55 cases were considered idiopathic. Specific IgE to fish (> 0.7 kU/l) was found in two patients, but only one was diagnosed as having fish allergy. We concluded that A. simplex is an important etiologic factor in acute urticaria. We suggest that it should be considered in cases of urticaria/AE or anaphylaxis, especially after fish ingestion.

Adolescent↗

Eosinophil-derived proteins in postprandial (food-dependent) exercise-induced anaphylaxis.

BACKGROUND: Postprandial exercise-induced anaphylaxis (PPEIAn) is a form of EIAn in which the ingestion of food before the exercise is associated with the onset of symptoms. Skin reactivity and the presence of specific serum IgE to several food allergens suggest the occurrence of food-dependent allergic mechanisms. METHODS: In order to study the involvement of eosinophils in the pathogenesis of PPEIAn we measured the changes in serum eosinophil cationic protein (ECP) and eosinophil protein X/eosinophil-derived neurotoxin (EPX/EDN) levels in 6 patients with PPEIAn, subjected to three separate challenges with either suspected foods only, exercise after a meal without or with suspected food ingestion. RESULTS: We found serum levels of both eosinophil-derived proteins increased only in challenges including both exercise and suspected food ingestion. Symptoms of anaphylaxis occurred in 3 of these patients. CONCLUSIONS: The increased release of eosinophil basic proteins in PPEIAn patients, caused by physical exercise following ingestion of suspected foods, is not obligatory for the definition of the syndrome.

Adolescent↗

CD8+ T lymphocytes provide helper activity for IgE synthesis in human immunodeficiency virus-infected patients with hyper-IgE.

Increased levels of serum IgE and eosinophilia have been described in human immunodeficiency virus (HIV) infection, almost exclusively in patients with CD4+ cell count < 200 cells/microliters. IgE production is regulated by CD4+ T helper type 2 (Th-2) lymphocytes, producing interleukin 4 (IL-4) and expressing a ligand for the B cell-specific CD40 molecule (CD40 ligand [L]). A shift to a Th-2-like pattern of cytokine secretion has been postulated to be associated with progression toward acquired immunodeficiency syndrome (AIDS). We studied three AIDS patients with very high levels of IgE and almost complete depletion of CD4+ lymphocytes, suggesting that IgE synthesis could not be driven by CD4+ cells. IgE in vitro synthesis by cells from such patients was, however, inhibited by anti-IL-4. We show that both CD8+ T cell lines and the majority of CD8+ T cells clones derived from these patients produce IL-4, IL-5, and IL-6 in half of the cases together with interferon gamma (IFN-gamma). 44% of CD8+ T cell clones expressed a CD40L, and the supernatants of the clones were capable of inducing IgE synthesis by normal B cells costimulated with anti-CD40. CD8+ T cells in these patients therefore functionally mimic Th-2 type cells and may account for hyper-IgE and eosinophilia in the absence of CD4+ cells. The presence of such CD8+ cells may also provide a source of IL-4 directing the development of predominant Th-2 responses in HIV infection.

Acquired Immunodeficiency Syndrome↗

Immunologic aspects of hyperimmunoglobulinemia E-like syndrome in patients with AIDS.

In this study we describe a series of nine patients affected by acquired immunodeficiency syndrome (AIDS) or AIDS-related complex who had hypereosinophilia and hyperimmunoglobulinemia E (hyper-IgE) with chronic dermatitis and recurrent staphylococcal infections. These patients had features similar to those present in hyper-IgE syndrome, a primary immunodeficiency disease. In addition, immunologic characterization of these patients with human immunodeficiency virus (HIV) infection, compared with 51 HIV-positive patients without hyper-IgE, both atopic and nonatopic, and three patients affected by the primary hyper-IgE syndrome, also revealed an increase in IgA and a severe decrease in B and CD4+ lymphocytes. Spontaneous in vitro synthesis of IgE by peripheral blood mononuclear cells was confirmed in both hyper-IgE conditions, together with increased levels of circulating eosinophil cationic protein. Serum-soluble CD23, usually increased in atopic conditions and hyper-IgE, was similar to that of normal control subjects in the HIV-positive patients with hyper-IgE. On the basis of our findings, we conclude that a hyper-IgE-like syndrome represents a distinct aspect of the clinical manifestations associated with HIV infection and that the immunologic mechanisms in this condition seem to differ from those known in primary hyper-IgE syndrome, because CD4+ TH2 type cells, which are currently believed to have a role in IgE production, are severely depleted in HIV-positive patients.

AIDS-Related Complex↗

Expansion of CD11abright cells in CD8+CD45RA+ from HIV-infected patients: a new early marker for disease progression?

CD8+CD45RA+ T lymphocytes present two distinct subpopulations expressing the CD11a molecule (LFA-1 alpha chain) with different intensity. CD11adim cells represent the unprimed population within the CD8+CD45RA+ subset, whereas CD11abright cells are activated and may be considered as memory lymphocytes. The aim of this study was to analyze the expression of CD11a and CD18 within the CD8+CD45RA+ population in young HIV-infected individuals at different stages of disease as a marker of activation and of disease progression. Blood cells from 82 HIV-infected individuals and 23 age-matched healthy controls were stained with unconjugated CD11a, CD18, PE-goat F(ab')2 anti-mouse, FITC-CD45RA, and TRI-Color CD8. Quantitative analysis for three-color immunofluorescence was carried out by flow cytometry. HIV+ subjects were subdivided into three groups according to their CD4+ cell number (group A, CD4+ cells > 500/microliters [20 subjects], group B, CD4+ cells between 500 and 200/microliters [36 subjects], and group C, CD4+ lymphocytes < 200/microliters [26 subjects]). We found a significant increase of CD11abright in the CD8+CD45RA+ subpopulation throughout the progression of the disease. The CD11abright percentage of positivity (mean) within the CD8+CD45RA+ subpopulation was 31% in healthy donors, 51% in group A, 52% in group B, and 68% in group C. CD11abright expression was closely related to CD18bright (p < 0.001), but not to CD38. The relative increase of CD11a and CD18 expression in CD8+CD45RA+ T lymphocytes parallels the decrease of CD4+ cells and the progression of disease: an inverse correlation between the percentages of CD4+ cells/microliter and CD8+CD45RA+CD11abright cells (p < 0.001) and a direct correlation between the number of CD4+ lymphocytes per microliter and both the number of CD8+CD45RA+CD11adim cells (p < 0.001) and the number of CD8+CD45RA+CD11abright (p = 0.002) was observed. The relative increase of CD8+CD45RA+CD11abright cells may represent an additional marker for monitoring HIV-induced immunodeficiency.

Adult↗

Intranasal immunotherapy with Dermatophagoides extract: in vivo and in vitro results of a double-blind placebo-controlled trial.

Intranasal immunotherapy (IT) has been proposed as a means to induce an effective immunity of the nasal mucosa in patients with allergic rhinitis, avoiding systemic side effects. In the present study 20 individuals with chronic allergic rhinitis, and skin prick test reactive to Dermatophagoides pteronyssinus (DP) only, were randomized and subjected to a three months' double-blind placebo-controlled trial of intranasal IT with DP extract. All patients received also sodium cromoglycate as pre-medication. Before and at the end of the treatment the patients performed specific nasal provocation tests, and samples of serum and nasal secretions were collected to measure total and specific IgE, levels of eosinophil cationic protein (ECP), and mast-cell-derived tryptase. A clinical score was computed by the symptoms indicated by the patients. The clinical score did not change in the two groups after the treatment, whereas a decrease in nasal reactivity was observed. Total IgE increased only in secretions from placebo-treated patients, but were not modified in sera. IgE to DP in sera and nasal secretions did not change significantly. Tryptase levels in nasal secretions decreased in both groups, while ECP was unchanged after IT. Serum ECP levels decreased more in actively treated patients than in the placebo group. The data suggest that changes of IgE and inflammatory mediators may be affected by the use of sodium cromoglycate in both groups, but some parameters change early in different directions in IT- and placebo-treated groups.

Administration, Intranasal↗