Search

Anaphylaxis after mosquito bite is rare, but life threatening. No approved preventive therapy is available to date, but omalizumab could be a promising therapeutic option for reducing risk and improving quality of life in these patients.

President John F. Kennedy (JFK) had a complex medical history that is now thought to be an autoimmune polyglandular syndrome type 2 with Addison’s disease and hypothyroidism. He also had gastrointestinal symptoms from adolescence, which now fit well with coeliac disease. In addition, he had a chronic back problem, which contributed to a chronic pain syndrome. This review looks at JFK’s various diseases and focusses on the history of coeliac disease, as well as its presentation. JFK’s Irish ancestry supports the hypothesis of a coeliac disease started early in his youth.

Introduction: It is acknowledged that any claim of efficacy of allergen immunotherapy must be done for each specific product, and this remains true also for venom immunotherapy (VIT). Thus, we evaluated the efficacy and safety of a specific tyrosine-adsorbed VIT for vespula spp. and honeybee in real-life. Methods: Consecutive patients diagnosed with hymenoptera allergy, and receiving VIT for either vespula or honeybee with a tyrosine-adsorbed preparation were observed to evaluate the grade of reaction (according to Muller) at the first field re-sting. A modified ultra-rush protocol was used. Results: A total of 247 patients (73 female) were observed (102 honeybee, group H, 145 vespula, group V). Seventy-five patients in group H had a re-sting, and 74/75 had a lower grade reaction at re-sting as compared to the pre-VIT reaction. Considering systemic reactions, protection was achieved in 89% of patients. In group V 118 patients were re-stung, and 76/118 patients with previous grade III-IV reaction had no more systemic reaction under VIT. Overall, considering systemic reactions, protection was achieved in 92% of subjects. Of note, in both groups there was a clear inverse correlation between the severity of pre-VIT and during VIT reactions. The duration of VIT at the time of re-sting did not affect the efficacy. The safety was overall good, with 18% ad 15.4% local reactions in groups H and V, respectively. Discussion: Modified extracts, including tyrosine-absorbed, have the aim of improving the safety of VIT still yet maintaining the efficacy. Field re-sting is the best way to assess the efficacy in real life. In this observational study we could confirm the protective efficacy of the tyrosine-adsorbed extract, with a good safety expecially in the build-up using a modified-rush protocol. Conclusion: The tyrosine-adsorbed VIT used herein is a viable and advantageous form of treatment for hymenoptera allergy. Keywords: Hymenoptera venom allergy, Venom immunotherapy, Tyrosine adsorbed, Efficacy, Safety, Systemic reaction, Field re-sting

none 6 no Background: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods: From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results: In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions: This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. none Volta U;Bardella MT;Calabrò A;Troncone R;Corazza GR;Study Group for Non-Celiac Gluten Sensitivity Volta U;Bardella MT;Calabrò A;Troncone R;Corazza GR;Study Group for Non-Celiac Gluten Sensitivity

Background: Shrimp is a frequent cause of food allergy worldwide. Besides tropomyosin, several allergens have been described recently. Objective: We investigated which allergens are involved in Italian shrimp-allergic adults. Methods: Sera from 116 shrimp-allergic patients selected in 14 Italian allergy centers were studied. Skin prick tests with house dust mite (HDM) as well as measurements of IgE to Pen a 1 (shrimp tropomyosin) and whole shrimp extract were performed. All sera underwent shrimp immunoblot analysis, and inhibition experiments using HDM extract as inhibitor were carried out on some Pen a 1-negative sera. Results: Immunoblots showed much variability. IgE reactivity at about 30 kDa (tropomyosin) was found in 90 kDa was frequent. Further reactivities at 14–18, 25, 43–50, about 60 and about 80 kDa were detected. Most subjects had a history of shrimp-induced systemic symptoms irrespective of the relevant allergen protein. IgE to Pen a 1 were detected in sera from 46 (41%) patients. Skin reactivity to HDM was found in 43/61 (70%) Pen 1-negative subjects and inhibition studies showed that pre-adsorption of sera with HDM extract induced a marked weakening of the signal at >67 kDa. Conclusions: Several allergens other than tropomyosin are involved in shrimp allergy in adult Italian patients. Some hitherto not described high molecular weight allergens seem particularly relevant in this population and their cross-reactivity with HDM allergens makes them novel potential panallergens of invertebrates.

International audience; Background: In ascertained allergic sensitization to Vespa crabro (VC) venom, the European guidelines still consider venom immunotherapy (VIT) with Vespula (VE) venom sufficient to achieve an adequate protection against VC. However, antigen 5 immunoblotting studies showed that a genuine sensitization to VC venom may exist. In such cases, a specific VC venom would be preferable for VIT treatment. Since in the last few years, VC venom extracts became available for diagnosis and desensitization, we assessed the efficacy and safety of VIT with a VC-VIT, compared to VE extract. Methods: Patients stung by VC, and carefully diagnosed for specific sensitization and indication to VIT underwent a 5-year course of immunotherapy with either VE or VC extracts. The severity of reactions at the first sting (pre-VIT) and after field re-stings (during VIT) were compared. Results: Eighty-three patients, treated with VE extract and 130 patients treated with VC extract completed the 5-year course of VIT. Only a fraction of those patients (43,8%) were field-re-stung by VC: 64 patients on VC VIT and 69 on VE VIT. In the VC VIT group, reactions at re-sting were: 50 negative, 12 large local reactions, 4 systemic reactions (Muller grade I). In this group the VC VIT efficacy was 93,8%. In the VE VIT treated group the reactions at VC re-sting were: 51 negative, 10 large local reactions and 9 systemic reactions (5 Muller I, 3 Mueller III, 1 Muller IV). In this group the overall efficacy of VIT was 87,0%. The difference in efficacy between the two groups was not statistically significant, as previously reported in literature. Nonetheless, field sting systemic reactions Muller III and IV were recorded only in those patients receiving VE VIT. Conclusion: This observation suggests that in patients with ascertained VC-induced allergic reactions a specific VC VIT, where available, would be more adequate, at least concerning the safety profile.

Background Sublingual immunotherapy (SLIT) proved effective and safe in respiratory allergy, and thus its use in hymenoptera allergy can be hypothesized. Objective We sought to assess, in a proof-of-concept study, whether SLIT might potentially be beneficial in hymenoptera allergy. The sting challenge in large local reactions (LLRs) was used to test this hypothesis. Methods We performed a randomized, double-blind, placebo-controlled study involving patients with LLRs who were monosensitized to honeybee. After the baseline sting challenge, they were randomized to either SLIT or placebo for 6 months. The treatment (Anallergo, Florence, Italy) involved a 6-week build-up period, followed by maintenance with 525 μg of venom monthly. The sting challenge was repeated after 6 months. Results Thirty patients (18 male patients; mean age, 44.5 years) were enrolled, and 26 completed the study, with 1 dropout in the active group and 3 dropouts in the placebo group. In the active group the median of the peak maximal diameter of the LLRs decreased from 20.5 to 8.5 cm ( P = .014), whereas no change was seen in the placebo group (23.0 vs 20.5 cm, P = not significant). The diameter was reduced more than 50% in 57% of patients. One case of generalized urticaria occurred in a placebo-treated patient at sting challenge. No adverse event caused by SLIT was reported. Conclusion Honeybee SLIT significantly reduced the extent of LLRs, and its safety profile was good. Although LLRs are not an indication for immunotherapy, this proof-of-concept study suggests that SLIT in hymenoptera allergy deserves further investigation. Trials involving systemic reactions and dose-ranging studies are needed.

Phytohemagglutinin (PHA)-induced human T cell clones (TCC) derived from conjunctival flogistic tissues of 3 patients with vernal conjunctivitis produced unusually high amounts of interleukin-4 (IL-4) and no, or limited amounts of, gamma-interferon (IFN-γ). Allergen (Dermatophagoides pteronyssinus or Lolium perenne group I)-specific TCC derived from peripheral blood of two atopic donors produced significantly higher amounts of IL-4 and significantly lower amounts of IFN-γ than TCC specific for bacterial antigens (tetanus toxoid and PPD) contemporarily established from the same donors. These data provide evidence for a compartimentalization of Th2-like helper T cells in target organs and in the allergen-specific T cell repertoire of allergic patients. Non-B, non-Tbone marrow cells could produce IL-4, but not IL-2 or IFN-γ, in response to cross-linkage of Fcε type I receptors. These cells may further contribute to the maintenance and amplification of allergic inflammation.

Background Subjects with a history of documented penicillin allergy but with negative skin test results for cephalosporins, can tolerate subsequent challenge doses of cephalosporin without an allergic reaction. [1]. In immediate reactions to betalactams (BL), in some instances, specificity was mainly directed to the BL inducing the reaction, but in other cases specificity was mainly directed to another structure, probably related with previous BL exposure [2].

We investigated the infection of peripheral blood mononuclear cells (PBMNC) by hepatitis C virus (HCV) in 5 patients with HCV-related chronic hepatitis. The presence of HCV-RNA-positive and -negative strands was tested with the polymerase chain reaction (PCR) method. In all subjects, HCV-RNA was shown in PBMNC. In 3 cases, HCV-RNA was shown in the T- and B-cell populations, with viral RNA also present in the monocyte-macrophage fraction of two of these. HCV-RNA-negative stranded molecules, indicative of the viral multiplication, were significantly increased in cells maintained in cultures with PHA/PMA stimulation. The results indicate that HCV infect blood mononuclear cells, thus suggesting that this cellular tropism may play a role in HCV infection.

Publisher Summary Despite the great progress that has been achieved in recent years in the diagnosis and treatment of Hodgkin's lymphoma, the etiopathogenesis of this disease still remains obscure. Definite proof that Hodgkin's disease (HD) is a malignant neoplasm, albeit a remarkably atypical one, has been provided during the past two decades by a number of cytogenetic, immunological, and molecular biology studies. Several fundamental issues, however, still remain open. They include the genesis of the immune deficiency, the nature of the normal counterpart of the neoplastic cells, and the role of other tumor-infiltrating lymphocytes. This chapter describes the immunological alterations found in untreated HD patients, mainly focusing on those involving the T and B cell compartments. The chapter also discusses the hypotheses on the origin of Reed–Sternberg (RS) cells and describes the role of the cells surrounding them in involved lymphoid organs.

Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.

Studies of human IgE synthesis are summarized and provide further insight into the cellular and molecular mechanisms involved in IgE regulation, as well as in the alterations responsible for IgE disregulation in some pathological conditions. These include the demonstration that IL-4 is the essential factor for the induction of human IgE syntheses. Another T cell-derived lymphokine, IFN-gamma negatively regulated the IgE synthesis induced by IL-4. These two lymphokines can be produced by different T helper cells, as shown in mice, but they can also be the product of the same T cells clones. Additional cellular and/or molecular signals appear to be involved in the IL-4-induced IgE synthesis, but their precise role in this process is undetermined. Finally, alternations of one or more of these regulatory mechanisms can be detected in patients with pathological conditions characterized by hyperproduction of IgE. In particular, the increased prevalence of T cells clones able to produce IL-4 appears to be a distinctive feature of patients with common atopy whereas a reduction in the proportion of IFN-gamma-producing T cells seems to be peculiar of both patients with hyper-IgE syndrome and patients with AIDS.

T Lymphocytes from thyroid infiltrates and peripheral blood (PB) of 3 patients with Hashimoto's thyroiditis (HT) were cloned using a microculture system previously shown to allow the clonal expansion of virtually all PB T lymphocytes from normal individuals. The phenotypic and functional features of a total number of 153 clones from thyroid infiltrates and 206 clones from PB were examined and compared with those of 272 clones derived from normal PB and spleens. The majority of clones derived from thyroid infiltrates of patients with HT had the cytotoxic/suppressor (T8+) phenotype, whereas the majority of clones from PB expressed the helper/inducer (T4+) phenotype. In addition, a consistent proportion (25%) of clones derived from PB of one patient had a phenotype (T3+T4-T8-) that was only occasionally found on clones obtained from PB or spleens of normal subjects. Most clones derived from both PB and thyroid infiltrates of the patients with HT had cytolytic activity, assessed by a lectin-dependent cytolytic assay against the murine P815 tumor cell line. The high frequency of cytotoxic T cells in thyroid infiltrates was related to the increased proportion of T8+ cells, whereas enhanced percentages of cytotoxic cell precursors with T4+ and T3+T4-T8- phenotypes primarily accounted for the high frequency of cytolytic T cells in the PB of the same patients. Many cytolytic T cell clones derived from thyroid infiltrates also had natural killer activity against human K562 and MOLT-4 target cells. These data provide the first functional analysis of T lymphocytes infiltrating the thyroid gland in patients with HT and suggest that the high proportions of cytolytic T cell precursors found in both thyroid infiltrates and PB of these patients may be of importance in determining the tissue damage in thyroid autoimmune disease.

Levels of IgE protein and IgE antibodies specific for 8 different allergenic extracts were measured in the serum of a large series of patients infected by the human immunodeficiency virus (HIV) and in HIV-seronegative subjects belonging to the same risk groups (intravenous drug-users, homosexual men and hemophiliacs). The proportion of subjects showing elevated IgE levels was higher among HIV-infected patients with group IV disease than among HIV-infected patients with group II-III diseases or seronegative individuals. In addition, many HIV-infected patients with elevated IgE levels showed the presence in their serum of IgE antibodies specific for fungal antigens.

Supernatants (SN) from 10 phytohemagglutinin (PHA)-stimulated human T cell clones (TCC), selected for their helper function on IgE synthesis, were found to provide IgE helper activity in atopic B cells showing low or undetectable spontaneous in vitro IgE synthesis. In contrast, SN from 5 PHA-stimulated TCC unable to provide helper function for IgE synthesis consistently failed to elicit IgE production. SN active on IgE synthesis contained high concentrations of interleukin-4 (IL-4), whereas inactive SN did not contain detectable amounts of IL-4. Moreover, the IgE helper activity of TCC SN was strongly inhibited by the addition of interferon-gamma (IFN-gamma) to B cell cultures. These data suggest that IL-4 may play a role in the induction of in vitro human IgE synthesis, whereas IFN-gamma displays an inhibitory effect.

A total of 76 T-cell clones established from peripheral blood (PB) of 2 patients with the acquired immune deficiency syndrome (AIDS) and of 141 T-cell clones established from PB of 3 normal donors were compared for their ability to produce interleukin 2 (IL-2) and gamma-interferon (gamma-IFN). Twenty-seven clones from AIDS patients and 85 clones from controls expressed the CD4 phenotype, whereas 49 clones from AIDS patients and 56 clones from controls expressed the CD8 phenotype. There were no significant differences in the proportions of IL-2-producing CD4 T-cell clones established from PB of patients with AIDS and controls, but the mean concentration of IL-2 produced by CD4 clones from AIDS patients was significantly lower than that produced by CD4 clones from controls. Both the proportion of gamma-IFN-producing CD4 clones and the mean concentration of gamma-IFN produced by CD4 clones were significantly lower in AIDS patients than in controls. In contrast, there were no differences between AIDS patients and normal individuals in the proportion of IL-2- or gamma-IFN-producing CD8 clones, or in the mean concentration of IL-2 and gamma-IFN produced by CD8 clones. These data suggest that the reduced ability of PB T-cells from patients with AIDS to produce IL-2 and gamma-IFN is not simply due to altered proportions or numbers of T-cell subpopulations, but also reflects intrinsic abnormalities of individual CD4 T lymphocytes.