An atlas of IgE sensitization patterns in different Italian areas. A multicenter, cross-sectional study.

Summary: Background. The development of recombinant technology supported the allergy diagnostic work-up in the daily clinical practice, representing a useful tool for epidemiological studies. Methods. An atlas of the IgE sensitization profiles found throughout Italy was prepared from a nationwide, multicenter, cross-sectional study. Results. 6052 unselected consecutive individuals, belonging to North-West [NW], North-East [NE], Centre [C], South [S], and Islands subset [Is] were evaluated by means of the ImmunoCAP ISAC test. The top-ranked sensitizations found were Cup a 1 in [C] (58.1%) and [S] (53.6%), Phl p 1 in the North (from 46.1% to 49%), and Cyn d 1 in [Is] (44.2%). High frequency of house dust mite group 2 molecules sensitization was found in [C] (36.9%) and [S] Italy (40.8%), whilst low level of reactivity was recorded in [NW] (20%). Pellitory hypersensitivity was mainly found in [C], [S], and [Is], whilst ragweed Amb a 1 sensitivity was particularly found in [NW] Italy. IgE recognition of PR-10, Profilin, and nsLTP was mutually exclusive in 69.1% of cases, PR-10 reactivity mostly occurring in [NE], Profilin in [NW], and nsLTP molecules recognition mainly recorded in [C] and [S]. Conclusions. Divergent IgE sensitization patterns were found along Italy, possibly linked to the distinct geographical locations, indicating multiplex system IgE analysis as a reliable approach for epidemiological evaluation even in small geographical areas.

Pla a 2 and Pla a 3 reactivities identify plane tree-allergic patients with respiratory symptoms or food allergy.

Nine hundred and thirty-nine rPla a 1, nPla a 2, and rPla a 3 ImmunoCAP ISAC reactors were studied. nPla a 2pos MUXF3pos but Pla a 1/2neg subjects were excluded from the study because they were cross-reactive carbohydrate determinant reactors. Among the 764 remaining participants, 71.9% were Pla a 3pos , 54.1% Pla a 2pos , and 10.9% Pla a 1pos . Among Pla a 3 reactors, 89.6% were Pru p 3pos and 86.8% Jug 3pos , but the strongest IgE recognition relationship was observed between Pla a 3 and Jug r 3. Distinctive clinical subsets could be documented among plane tree-allergic patients. Pla a 3 reactors had both local and systemic food-induced reactions, but lower past respiratory symptoms occurrence. Pla a 2 reactivity was associated with respiratory symptoms but inversely related to systemic reactions to food. Cosensitization to Pla a 2 and Pla a 3 was associated with a lower past incidence of severe food-induced reactions.

Lipid transfer protein sensitization: reactivity profiles and clinical risk assessment in an Italian cohort.

BACKGROUND: Nonspecific lipid transfer proteins (nsLTPs) represent a major cause of systemic food allergic reactions in the Mediterranean area. This study investigate hierarchical patterns and cluster relationships of IgE sensitization to different nsLTPs, and the relationship to clinical allergy in a large Italian cohort. METHODS: A total of 568 nsLTP-positive subjects after IgE ImmunoCAP-ISAC microarray analysis with Ara h 9, Art v 3, Cor a 8, Jug r 3, Pla a 3, Pru p 3 and Tri a 14 allergens were studied. IgE inhibition experiments were carried out with mugwort and plane tree pollen extracts. RESULTS: Eighty-two per cent of nsLTP-positive participants (94% if <6 years old) were Pru p 3(pos) , and 71% were Jug r 3(pos) . Participants who reacted to >5 nsLTPs reported a higher incidence of food-induced systemic reactions. Only Art v 3 and Pla a 3 (mugwort and plane tree nsLTPs, respectively) were associated with respiratory symptoms, and a correlation was observed between sensitization to pollen and plant food nsLTPs, particularly between Pla a 3 and tree nut/peanut nsLTPs. Co-sensitization to Par j 2 and PR-10 or profilin pan-allergens was associated with a lower prior prevalence of severe food-induced reactions. In inhibition assays, plane and mugwort pollen extracts inhibited 50-100% of IgE binding to food nsLTPs in microarrays. CONCLUSIONS: Testing IgE reactivity to a panel of nsLTP allergens unveils important associations between nsLTP sensitization profiles and clinical presentation and allows the identification of novel cluster patterns indicating likely cross-reactivities and highlighting potential allergens for nsLTP immunotherapy.

Phase II controlled trial of post-exposure immunization with recombinant gp160 versus antiretroviral therapy in asymptomatic HIV-1-infected adults. VaxSyn Protocol Team.

OBJECTIVE: To alter the natural course of HIV-1 infection by inducing or potentiating immune responses to HIV-1 envelope glycoprotein. DESIGN: Multicentre, double-blind, three-arm, placebo-controlled study. SETTING: Outpatients attending clinics in two University Hospitals. PATIENTS: Ninety-nine asymptomatic HIV-1-infected adults with CD4+ T-cell counts > 400 and < 600 x 10(6)/l and no previous antiretroviral therapy were included. INTERVENTIONS: Patients were randomly assigned to three groups treated with: (i) gp160 in alum over a 2-year period in combination with placebo for the full study duration (n = 32); (ii) gp160 in alum over a 2-year period in combination with zidovudine for the full study duration (n = 34); and (iii) alum over a 2-year period in combination with zidovudine for the full study duration (n = 33). RESULTS: Immunotherapy was well tolerated and no significant differences in disease progression were seen in the treatment groups. The majority of patients (85%) receiving gp160 showed persistent lymphoproliferative responses to the immunogen and to a different Env antigen preparation. CD4+ cell count changes in patients receiving zidovudine alone were significantly higher than those seen in patients receiving immunotherapy alone after 1 year of treatment. Zidovudine administration was associated with initial transient reduction of plasma viraemia. CONCLUSIONS: Prolonged immunization with a soluble HIV-1 subunit provided no benefit to asymptomatic HIV-1-infected patients and was inferior to zidovudine monotherapy. Furthermore, immunization with gp160 shortened the duration of the transient viral load reduction induced by zidovudine.

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.

Occupational generalised urticaria and allergic airborne asthma due to anisakis simplex.

Anisakis simplex (AS), a fish and cephalopodes parasite, may cause allergic reactions in humans on eating and/or handling contaminated fish. We present a case of occupational hypersensitivity to AS in a woman employed in a frozen-fish factory. She showed both generalised urticarial rash and asthmatic symptoms after work place exposure. All these symptoms immediately disappeared after work place exposure was ceased. The presence of a positive skin prick test and high specific IgE values confirmed a hypersensitivity to anisakis. This is the first case reported of both occupational generalised urticaria and allergic airborne asthma due to AS in the same patient. We suggest that AS could be an important cause of occupational asthma and/or urticaria in the fish industry.

Occupational asthma due to metoclopramide hydrochloride (MCPH).

Metoclopramide hydrochloride (MCPH) is dopamine antagonist antiemetic drug that binds D2 receptor at the central nervous system and peripheral levels, which stimulates the upper gastrointestinal tract motility. It is often used in the management of some forms of nausea and vomiting (1-3). Occupational allergy to drugs is seldom reported. No case of occupational allergy to MCPH have been reported, to date. We present a case of airborne allergic asthma in a worker employed in the synthesis of Metoclopramide hydrochloride.

Proliferative and cytotoxic responses to mannoproteins of Candida albicans by peripheral blood lymphocytes of HIV-infected subjects.

Mucosal candidiasis is one of the first opportunistic diseases in HIV-infected subjects. In order to understand the relationship between this disease and immunodeficiency to chemically defined, immunodominant Candida antigens, a mannoprotein fraction from C. albicans cell wall (GMP) was used to analyse proliferative and non-MHC-restricted cytotoxic responses of peripheral blood mononuclear cells (PBMC) from normal and HIV-infected subjects. In the former, GMP induced extensive blastogenesis, generation of powerful cytotoxicity against a tumour cell line (K562), and production of substantial amounts of interferon-gamma (IFN-gamma). Cultured PBMC from HIV-infected subjects manifested an early decreased ability for proliferative as well as differentiative cytotoxic responses to the candidal mannoproteins. This inability became clearly evident in subjects with stage III (CDC) of the disease, was total in CDC stage IV and occurred even in some subjects with a normal number of CD4+ cells. Low or absent response to GMP correlated with lack of response to tetanus toxoid. In contrast, both lymphoproliferative and cytotoxic responses to exogenous IL-2 was highly preserved at all stages of infection. The production of IFN-gamma in GMP-stimulated PBMC cultures critically fell to negligible values in most of the subjects in CDC stages II and III. Thus, the lowered or absent cell-mediated immune responses to candidal mannoprotein may be one factor to explain the early, elevated susceptibility of HIV-infected subjects to mucosal candidiasis. This study also shows that our mannoprotein preparation may be used as a probe to detect the overall efficiency of T cell responses in the above subjects.

Distinct delayed T-cell response to beta-methasone and penicillin-G in the same patient.

BACKGROUND: Multiple drug allergy syndrome is a clinical condition characterized by reactions against more than one different class of, both pharmacologically and structurally, unrelated drugs. Scanty data are available to date about a multiple drug delayed hypersensitivity syndrome. Our aim was to report the case of a delayed reaction to both beta-methasone (beta-MT) and penicillin-G (pen-G) occurring in the same patient, and analyse beta-MT- and pen-G-specific T-cell Lines (TCLs) with regard to their specificity, phenotype and cytokine profile. METHODS: We generated two drug-specific TCLs from biopsies at the site of positive intradermal reactions, and analysed their immunophenotype, T-cell receptor Vbeta (TCR-Vbeta) domains expression and cytokine profile. RESULTS: We demonstrated the specificity of the T cells isolated from positive intradermal test reactions to pen-G and beta-MT through the strict dose-dependent proliferation in response to drug-pulsed autologous antigen presenting cells. Fluorescence activated cell sorter (FACS) analysis revealed a predominance of CD4+ cells in the inflammatory cell infiltrate of intradermal test with beta-MT, while a predominance of CD8+ T cells in the site of delayed reaction to pen-G was found. The drug specific CD4+ and CD8+ T cells were heterogeneous, with regard to TCR-Vbeta usage. CD8+ pen-G-TCL displayed a preferential T helper 2 (Th2) profile, while a substantially heterogeneous pattern of cytokine production characterized specific beta-MT TCL. CONCLUSION: The study describes the coexistence in the same patient of a delayed hypersensitivity to both penicillin G and beta-MT, driven, respectively, by pen-G-specificTh2-skewed CD8+ and beta-MT specificTh0 CD4+ T cells. This case further support the existence of a multiple drug allergy syndrome also for delayed hypersensitivity.

CD28 costimulation and T lymphocyte proliferative responses in HIV-1 infection.

To investigate whether defective costimulatory signals could be involved in the loss of T lymphocyte functions during HIV-1 infection, we tested the effect of CD28 costimulation on both T cell receptor/CD3 and HIV-1 antigen-induced proliferative responses. Although CD3-mediated responses significantly decreased with more advanced stages of HIV-1 infection, the ability of potentiating the responses through CD28 costimulation was maintained at all stages and did not differ from that of HIV-1- subjects. When CD28 costimulation was studied in lymphocyte cultures stimulated with HIV-1 gp160 or p24, potentiation was seen only when a significant response was present without additional CD28 triggering, namely in subjects receiving active immunization with recombinant gp160. These results confirm the integrity of the CD28 pathway of costimulation during HIV-1 infection, and suggest that lymphocytes responding to soluble HIV-1 antigen are not deleted in HIV-1-infected patients, but do not receive significant priming during the natural course of the infection.

HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals.

In vitro lymphoproliferative responses to HIV-1 recombinant antigens (gp160, p24, and Rev protein) were studied in 83 patients with asymptomatic HIV-1 infection (CDC groups II and III) and circulating CD4 lymphocyte numbers > 400/mm3. Significant response to at least one of the three antigens was detected in 52.4% of the subjects, but the responses were weak, and concordance of the response to the three antigens was rare, the frequency of individuals responding to each antigen not exceeding 22.4%. Increasing frequencies of response were observed when recall antigens (tetanus toxoid and Candida albicans glycomannoprotein) (65.5%) and anti-CD3 MoAb (76.6%) were used as stimuli. Although a significant association between lymphocyte response to p24, but not gp160, and steadiness of CD4 lymphocyte numbers before the assay was observed, no predictive value for lack of CD4 cell decrease was confirmed for either antigen, and fluctuation of the responses to HIV antigens was seen during subsequent follow up. The panel of T cell assays used could be regarded as appropriate for monitoring both HIV-specific responses and T lymphocyte function during immunotherapy with soluble HIV antigens.

Long-term evaluation of cellular immunity during antiretroviral therapy and immunization with human immunodeficiency virus type 1 (HIV-1) Env glycoprotein in HIV-1-infected persons.

Cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens, microbial recall antigens, and CD3 monoclonal antibody were studied in HIV-1-infected asymptomatic patients in a phase II, double-blind trial of immunization with recombinant HIV-1 gp160 in or not in association with zidovudine. A vigorous and persistent lymphoproliferative response (LPR) to HIV-1 Env antigens was observed in vaccinated patients. Neither Env-specific lymphocyte cytotoxicity nor LPR to recall antigens was significantly influenced by gp160 administration. The induction of LPRs to HIV-1 envelope proteins did not show positive effects on the course of HIV-1 infection. Patients treated with zidovudine alone or in combination with the immunogen showed improvement of T lymphocyte responses and transient reduction of viremia. These results suggest that antiretroviral therapy is more beneficial than immunization with gp160 and should always be considered in association with future vaccination and immunotherapeutic interventions in HIV-1-infected subjects.

Hemoperitonio espontaneo agudo por ruptura de carcinoma primitivo de figado, tratado por hepatectomia do lobo esquerdo. / Acute spontaneous hemoperitoneum due to rupture of primary carcinoma of the liver treated by hepatectomy

Os autores apresentam um caso de hemoperitonio espontaneo por ruptura de carcinoma primitivo de figado, sendo controlado por hepatectomia do lobo esquerdo. Mostram o comprometimento hepatico apos a cirurgia, com evolucao de 5 meses. Assinalam que o presente caso e o primeiro a ser relatado na literatura nacional