C. Zanussi

Allergenic cross-reactivity among peach, apricot, plum, and cherry in patients with oral allergy syndrome: An in vivo and in vitro study

BACKGROUND Oral allergy syndrome in response to fruits and vegetables frequently occurs as clusters of hypersensitivity to members of the same botanical family, for which the immunologic basis lies in a number of common allergens, most of them still unidentified. OBJECTIVE This study was designed to assess the in vivo and in vitro cross-reactivity between fruits of the Prunoideae subfamily (i.e., peach, cherry, apricot, and plum) and to identify their major allergens and the cross-reactivity of the peach extract with grass and birch pollen. METHODS The in vivo study was conducted by skin prick tests and open food challenges with fresh fruits in 23 patients with oral allergy syndrome for peach and positive skin prick test and RAST results for the other Prunoideae. In vitro sodium dodecylsulfate-polyacrylamide gel electrophoresis was followed by immunoblotting and immunoblotting-inhibition. RESULTS A 13 kd component was identified as the only major allergen common to all the Prunoideae, the other major allergens were found at 14 kd in peach and at 30 kd in cherry. Immunoblotting inhibition showed wide cross-reactivity within the Prunoideae, whereas grass and birch pollen partially inhibited the peach blotting. CONCLUSIONS Clinical cross-reactivity to Prunoideae is essentially due to a common 13 kd IgE-binding component, which seems to be the most important major allergen of this subfamily, not shared with grass and birch pollen.

Studies on the relationship between the level of specific IgE antibodies and the clinical expression of allergy: I. Definition of levels distinguishing patients with symptomatic from patients with asymptomatic allergy to common aeroallergens

BACKGROUND The detection of specific IgE antibodies to environmental allergens does not always coincide with a diagnosis of clinically evident allergic disease, because some patients with positive skin and/or in vitro test results have no symptoms related to the allergen or allergens that induced the antibodies. OBJECTIVE In a multicenter study the optimal cutoff values for specific IgE antibody levels and skin test results that could discriminate between patients with symptomatic and those with asymptomatic allergy were determined. METHODS IgE antibodies specific for a panel of common aeroallergens were assayed with the Pharmacia CAP System (Pharmacia, Uppsala, Sweden) in two groups of patients, a group of 267 patients with symptomatic allergy and a group of 232 with asymptomatic allergy--both with positive skin prick test results--and in a group of 243 healthy, nonallergic control subjects. The cutoff values were established by receiver operating characteristic analysis. RESULTS A significantly higher mean specific IgE antibody value was found in patients with symptomatic allergy compared with patients with asymptomatic allergy (p < 0.001) and in patients with symptomatic allergy compared with healthy control subjects (p < 0.001). The optimal CAP System cutoff value between patients with symptomatic and those with asymptomatic allergy was 11.7 kU/L, and when seasonal allergens were compared with perennial allergens, the cutoffs were 10.7 kU/L and 8.4 kU/L, respectively. The optimal cutoff value for the skin prick test was a wheel area of 32 mm2 for seasonal allergens and 31 mm2 for perennial allergens. The skin test had a lower diagnostic value (sum of sensitivity and specificity) than the CAP System. CONCLUSIONS Cutoff values for specific serum IgE antibody levels are likely to be useful in clinical practice to distinguish symptomatic from asymptomatic allergy in patients with positive skin test results.

The PLAT Study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Principal results. PLAT Study Group. Progetto Lombardo Atero-Trombosi (PLAT) Study Group.

The Progetto Lombardo Atero-Trombosi (PLAT) Study was a prospective, multicenter, multidisciplinary study of the association among hemostatic variables, conventional risk factors, and atherothrombotic events in four groups of patients with preexisting vascular ischemic disease (335 myocardial infarction survivors, 123 patients with stable angina pectoris, 160 with transient ischemic attacks, and 335 with peripheral vascular disease). In the myocardial infarction group, univariate analysis showed that atherothrombotic events were associated with high fibrinogen (p = 0.001), factor VIII:C (p less than 0.001), and von Willebrand factor antigen (vWF:Ag) (p = 0.004) levels and with low high density lipoprotein cholesterol (p = 0.043), factor VII (p = 0.019), and protein C (p = 0.044) levels; multivariate analysis produced associations with high fibrinogen and factor VIII:C levels and low protein C levels. By both univariate and multivariate analysis, events in the angina pectoris group were associated with high vWF:Ag (p = 0.026) and leukocyte (p = 0.033) levels and the presence of carotid arterial stenosis (p = 0.063); associations with high leukocyte (p = 0.037) and factor VIII:C (p = 0.186) levels, family history (p = 0.031), and diabetes (p = 0.061) were also found in the group with transient ischemic attacks. In those with peripheral vascular disease, events were associated with Fontaine stage greater than or equal to IIB (p = 0.024), high factor VIII:C levels (p = 0.073), and low protein C (p = 0.028), fibrinogen (p = 0.030), antithrombin III (p = 0.054), and factor VII (p = 0.057) levels by univariate analysis and with Fontaine stage and low fibrinogen levels by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Secondary and Essential Cryoglobulinemias

The clinical and immunochemical classification of 166 patients with cryo-globulinemia are presented. 52% of the cryoglobulins were detected in patients hospitalized because of various causes. The most

Grass pollen immunotherapy: A single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis

Fifteen grass pollen--sensitive asthmatic patients were selected from 200 patients with grass pollenosis on the basis of positive SPTs and RASTs that were restricted to grass pollens (except Bermuda grass), no previous IT, and residence and occupation in an area monitored by serial pollen counts. They underwent a double-blind trial of specific IT with a mixture of three grass pollen--aqueous extracts (velvet, sweet vernal, and timothy) or placebo. After 10 mo, the mean maintenance dose of pollen extract (assayed by RAST inhibition) in eight actively treated patients was 6000 RAST units (range 3000 to 8000) and the mean total dose was 18,700 RAST units (range 10,200 to 30,000). Results were assessment done by the following clinical and immunological data: (1) during the pollen season, daily symptom scores; (2) PD 20% FEV1, IgE antibody to timothy by RAST in serum and in nasal secretions, serum IgG antibody to purified timothy allergen D by solid-phase radioimmunoassay, and the four IgG subclass antibodies by enzyme immunoassay were all measured before treatment and before and after the pollen season. Symptom scores of both treated patients and controls correlated with pollen counts (R = 0.88, p less than 0.05 and R = 0.71, p less than 0.05, respectively). There was a significant difference between the mean symptom score values of treated patients versus controls (Kruskal-Wallis test, p less than 0.001). No significant differences or changes either in the PD 20% FEV1 or IgE antibody to timothy in serum and nasal secretions were found in the two groups before or after IT.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-ASSOCIATED SUSCEPTIBILITY TO ACQUIRED IMMUNODEFICIENCY SYNDROME IN ITALIAN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

To investigate the contribution of genetic susceptibility to infection with human immunodeficiency virus, 50 subjects with lymphadenopathy syndrome (LAS) and 7 subjects with acquired immunodeficiency syndrome (AIDS) and Kaposis sarcoma were typed for HLA A, B, C, and DR antigens. The frequency of B35 was significantly higher in LAS patients who progressed to AIDS than in those who did not or in healthy controls. The association between DR5 and AIDS/Kaposis sarcoma was also confirmed in these patients.

Role of the elimination diet in adults with food allergy

The aim of the study was to check whether, after a period of complete exclusion of the offending foods in adult subjects suffering from food allergy, these foods could subsequently be safely reintroduced into the diet. Patients with chronic urticaria and/or perennial rhinitis negative for secondary pathology or other allergies were subjected to a strict diagnostic protocol for food allergy. Briefly, out of a case list of 207 patients, we found 23 patients whose symptoms were clearly related, on open reintroduction, to at least one food. The really offending foods in these patients were subsequently identified by double-blind, placebo-controlled food challenges. Only 10 of the 23 patients had positive challenges for 13 foods. Double-blind challenges were repeated after 1 year or more of avoidance of the offending foods to evaluate the persistence or disappearance of sensitivity. We found that five (38%) of the 13 previously offending foods were well tolerated. Thus, in adults, as previously proved in children, dietary avoidance of the offending foods appears to be an effective measure for dealing with food allergy. The kind of foods involved and the completeness of their avoidance appeared to be important factors favoring the reestablishment of tolerance in adults.

IL‐10 up‐regulates human monocyte phagocytosis in the presence of IL‐4 and IFN‐γ

Interleukin‐10 (IL‐10), a cytokine produced by type 2 belper T (Th2) cells, inhibits the microbicidal effector function of interferon‐γ (EFN‐γ)‐activated macrophages. However, recent observations indicate that IL‐10, like IFN‐γ, increases FcγRI expression and FcγR‐mediated cytotoxic activity on human monocytes, suggesting that this cytokine cannot be classified purely as a monocyte deactivator. The present study found that incubation for 40 h of human monocytes or monocyte‐derived macrophages in the presence of EL‐10 caused a significant enhancement of their capacity to ingest particles coated with immunoglobulin G (FcγR‐mediated ingestion) or with C3b/C3bi fragments of the complement system (GR1/CR3‐mediated ingestion). The number of phagocytosing cells (% phagocytosis) and the number of ingested particles per cell (phagocytic index) were both significantly higher after 40‐h incubation of monocytes with IL‐10 concentrations ≥1 U/ml. This up‐regulating activity on phagocytosis was completely reversed by anti‐EL‐10 monoclonal antibody (mAb). As previously reported, ILIO stimulated FcγRI expression on monocytes but did not induce the expression of FcγRII, FcγRIII, CR1, and CR3. IFN‐γ, like EL‐10, up‐regulated only FcγRI expression but significantly reduced both FcγR‐ and CR‐mediated ingestion. IL‐10 almost completely reversed the IFN‐γ‐induced inhibition of both FcγR‐ and CR‐mediated phagocytosis, without concomitant changes in membrane expression of phagocytic receptors. Exposure of monocytes to IL‐4 reduced the membrane expression of all three FcγRs and also inhibited FcγR‐mediated ingestion. On the other hand, IL‐4 up‐regulated both CR3 expression and CR‐mediated ingestion on cultured monocytes. IL‐10 not only neutralized the down‐regulatory effect of IL‐4 on FcγR expression but also completely reversed the IL‐4‐induced suppression of FcγR‐mediated phagocytosis. Exposure of monocytes to a combination of IL‐10 and IL‐4 resulted in a synergistic effect on CR‐mediated ingestion, even though no additive effects were observed on CR membrane expression. Finally, culture of monocytes in medium containing anti‐EL‐10 mAb significantly reduced their capacity to ingest IgG‐ or C3b/C3bi‐coated particles, suggesting a role for endogenously produced IL‐10 in the modulation of phagocytosis by human monocytes. These results demonstrate that IL‐10 is a potent up‐regulator of the phagocytic activity of human mononuclear phagocytes and indicate that this function may be in sensitive balance with the relative concentrations of EL‐10, IL‐4, and IFN‐γ.

Clinical and immunological effects of immunotherapy with alum‐absorbed grass allergoid in grass‐pollen‐induced hay fever

A double‐blind, placebo‐controlled study of immunotherapy was conducted in 19 patients with grass‐pollen hay fever to evaluate the efficacy and safety of a formalinized depot grass allergoid. The patients were assessed before and during IT by clinical (symptom‐medication scores during the grass‐ pollen season, specific nasal and skin reactivity) and immunological (specific IgE, IgG, IgG1 and IgG4 antibodies) parameters. High doses of grass allergoid, corresponding to a cumulative pre‐seasonal dosage of 46050 PNU, were administered, with only one systemic reaction. The actively treated patients had significantly lower symptom‐medication scores than placebo (p < 0.01) during the month of May and showed a significant decrease in specific skin (p < 0.01) and nasal (p < 0.05) reactivity, and a significant early increase in specific IgE (p < 0.01), IgG (p < 0.0005), IgG1 (p < 0.001) and IgG4 (p < 0.05), with a subsequent decrease of IgE and IgG1. No differences were detected in any of these parameters in the placebo group. A correlation was found between high IgG4/IgG1 ratio and the specific skin reactivity decrease (r = 0.691, p < 0.05), whereas a high IgG4/IgG1, ratio was associated with higher symptom‐medication scores (r = 0.654, p < 0.05). Possible explanations of these apparent discrepancies are proposed.

Interleukin-10 down-regulates oxidative metabolism and antibody-dependent cellular cytotoxicity of human neutrophils.

The authors investigated the ability of interleukin‐10 (IL‐10) to modulate some constitutive or interferon‐γ (IFN‐γ)‐enhanced activities of human neutrophils. An 18 h culture of neutrophils with IL‐10 dose‐dependently down‐regulated their capacity to produce O2− and lucigenin‐amplified chemiluminescence in response to n‐formyl‐methionyl‐leucylphenyl‐alanine (FMLP). Furthermore, treatment of neutrophils with IL‐10 decreased in a dose‐dependent fashion, their capacity to lyse antibody‐coated sheep erythrocytes. Membrane expression of FcγRI, FcγRII, FcγRIII, CR1, CR3 and FcγR‐ and CR‐mediated phagocytosis were not modified by the cytokine. Culture of neutrophils with IFN‐γ (100 U/ml) did not modify their FcγR‐ and CR‐mediated phagocytosis, but significantly up‐regulated FcγRI and CR3 membrane expression as well as their oxidative metabolism and antibody‐dependent cellular cytotoxicity (ADCC). When IL‐10 and IFN‐γ were added simultaneously to neutrophil culture, IL‐10 dose‐dependently reduced IFN‐γ‐induced increase of CR3 expression, O2− production (in response to both FMLP and phorbol 12‐myristate 13‐acetate, or PMA) and ADCC, but did not change FcγRI expression on phagocytes. These results demonstrate that IL‐10 is a significant neutrophil deactivator and provide new information on the role of IL‐10 in the regulation of neutrophil‐mediated inflammatory processes.