Daniela Gallerano

Persistence of IgE-Associated Allergy and Allergen-Specific IgE despite CD4+ T Cell Loss in AIDS

The infection of CD4+ cells by HIV leads to the progressive destruction of CD4+ T lymphocytes and, after a severe reduction of CD4+ cells, to AIDS. The aim of the study was to investigate whether HIV-infected patients with CD4 cell counts <200 cells/µl can suffer from symptoms of IgE-mediated allergy, produce allergen-specific IgE antibody responses and show boosts of allergen-specific IgE production. HIV-infected patients with CD4 counts ≤200 cells/µl suffering from AIDS and from IgE-mediated allergy were studied. Allergy was diagnosed according to case history, physical examination, skin prick testing (SPT), and serological analyses including allergen microarrays. HIV infection was confirmed serologically and the disease was staged clinically. The predominant allergic symptoms in the studied patients were acute allergic rhinitis (73%) followed by asthma (27%) due to IgE-mediated mast cell activation whereas no late phase allergic symptoms such as atopic dermatitis, a mainly T cell-mediated skin manifestation, were found in patients suffering from AIDS. According to IgE serology allergies to house dust mites and grass pollen were most common besides IgE sensitizations to various food allergens. Interestingly, pollen allergen-specific IgE antibody levels in the patients with AIDS and in additional ten IgE-sensitized patients with HIV infections and low CD4 counts appeared to be boosted by seasonal allergen exposure and were not associated with CD4 counts. Our results indicate that secondary allergen-specific IgE production and IgE-mediated allergic inflammation do not require a fully functional CD4+ T lymphocyte repertoire.

Natural clinical tolerance to peanut in African patients is caused by poor allergenic activity of peanut IgE.

In Africa, peanuts are frequently consumed, but severe allergic reactions are rare. We investigated immunological patterns of clinical tolerance to peanut in peanut‐sensitized but asymptomatic patients from central Africa compared to peanut‐allergic and peanut‐sensitized but asymptomatic patients from Sweden.

Rhinovirus-induced VP1-specific Antibodies are Group-specific and Associated With Severity of Respiratory Symptoms

Background Rhinoviruses (RVs) are a major cause of common colds and induce exacerbations of asthma and chronic inflammatory lung diseases. Methods We expressed and purified recombinant RV coat proteins VP1-4, non-structural proteins as well as N-terminal fragments of VP1 from four RV strains (RV14, 16, 89, C) covering the three known RV groups (RV-A, RV-B and RV-C) and measured specific IgG-subclass-, IgA- and IgM-responses by ELISA in subjects with different severities of asthma or without asthma before and after experimental infection with RV16. Findings Before infection subjects showed IgG1 > IgA > IgM > IgG3 cross-reactivity with N-terminal fragments from the representative VP1 proteins of the three RV groups. Antibody levels were higher in the asthmatic group as compared to the non-asthmatic subjects. Six weeks after infection with RV16, IgG1 antibodies showed a group-specific increase towards the N-terminal VP1 fragment, but not towards other capsid and non-structural proteins, which was highest in subjects with severe upper and lower respiratory symptoms. Interpretation Our results demonstrate that increases of antibodies towards the VP1 N-terminus are group-specific and associated with severity of respiratory symptoms and suggest that it may be possible to develop serological tests for identifying causative RV groups.

Comparison of the Specificities of IgG, IgG-Subclass, IgA and IgM Reactivities in African and European HIV-Infected Individuals with an HIV-1 Clade C Proteome-Based Array

A comprehensive set of recombinant proteins and peptides of the proteome of HIV-1 clade C was prepared and purified and used to measure IgG, IgG-subclass, IgA and IgM responses in HIV-infected patients from Sub-Saharan Africa, where clade C is predominant. As a comparison group, HIV-infected patients from Europe were tested. African and European patients showed an almost identical antibody reactivity profile in terms of epitope specificity and involvement of IgG, IgG subclass, IgA and IgM responses. A V3-peptide of gp120 was identified as major epitope recognized by IgG1>IgG2 = IgG4>IgG3, IgA>IgM antibodies and a C-terminal peptide represented another major peptide epitope for the four IgG subclasses. By contrast, gp41-derived-peptides were mainly recognized by IgG1 but not by the other IgG subclasses, IgA or IgM. Among the non-surface proteins, protease, reverse transcriptase+RNAseH, integrase, as well as the capsid and matrix proteins were the most frequently and strongly recognized antigens which showed broad IgG subclass and IgA reactivity. Specificities and magnitudes of antibody responses in African patients were stable during disease and antiretroviral treatment, and persisted despite severe T cell loss. Using a comprehensive panel of gp120, gp41 peptides and recombinant non-surface proteins of HIV-1 clade C we found an almost identical antibody recognition profile in African and European patients regarding epitopes and involved IgG-sublass, IgA- and IgM-responses. Immune recognition of gp120 peptides and non-surface proteins involved all four IgG subclasses and was indicative of a mixed Th1/Th2 immune response. The HIV-1 clade C proteome-based test allowed diagnosis and monitoring of antibody responses in the course of HIV-infections and assessment of isotype and subclass responses.

HIV-Specific Antibody Responses in HIV-Infected Patients: From a Monoclonal to a Polyclonal View

HIV infections represent a major global health threat, affecting more than 35 million individuals worldwide. High infection rates and problems associated with lifelong antiretroviral treatment emphasize the need for the development of prophylactic and therapeutic immune intervention strategies. It is conceivable that insights for the design of new immunogens capable of eliciting protective immune responses may come from the analysis of HIV-specific antibody responses in infected patients. Using sophisticated technologies, several monoclonal neutralizing antibodies were isolated from HIV-infected individuals. However, the majority of polyclonal antibody responses found in infected patients are nonneutralizing. Comprehensive analyses of the molecular targets of HIV-specific antibody responses identified that during natural infection antibodies are mainly misdirected towards gp120 epitopes outside of the CD4-binding site and against regions and proteins that are not exposed on the surface of the virus. We therefore argue that vaccines aiming to induce protective responses should include engineered immunogens, which are capable of focusing the immune response towards protective epitopes.

EFIS-EJI African International Conference on Immunity (AICI).

The EFIS-EJI African International Conference on Immunity (AICI: www.aici2011.org) took place from November 3 to November 7, 2011 in Victoria Falls, Zimbabwe, a meeting that is sponsored in part by the EFIS-EJI partnership beyond its typical European remit [1]. The central theme of the meeting was “Immunity in infectious diseases and allergy—diagnosis, treatment and prevention” and it was a follow-up to two earlier conferences at the same venue, one in 2007 whose theme was “Immunity: From deficit to excess” and the Fifth Congress of the Federation of African Immunological Societies (FAIS: www.faisoc.org) in 2003. The latter meeting was attended by representatives of the International Union of Immunological societies (IUIS) and its regional affiliates, the European Federation of Immunological Societies (EFIS), the Federation of Immunological Societies of Asia (FIMSA), and the Latin American Federation of Immunological Societies (ALAI). There is no doubt that the slogan of the IUIS, “Immunology without borders,” has been a driving force behind the meetings organized in Africa, which are intended to create a platform where international immunologists have the chance to discuss with those directly working in the field some of the most important immunologically mediated diseases that have high prevalence in this continent. In sub Saharan Africa, the world’s major infectious diseases have found a safe haven, causing untold human suffering, death, and economic devastation. The big three infectious diseases, HIV/AIDS, tuberculosis, and malaria, continue to be the commonest causes of illness and death. In addition to these, are diarrheal illnesses and respiratory infections other than tuberculosis. Furthermore, the prevalence rates of asthma, rhinitis, and allergic diseases are also increasing exponentially in this area, and traditional tropical infections such as schistosomiasis have not gone away. New infections including the pandemic influenza infections add to the disease burdens of these countries whose human and financial resources are limited. The thinking behind the EFIS-EJI AICI was to bring leading immunologists of the world together with health personnel who deal with the effects of these infectious diseases in order to create a platform that allowed the participants to appreciate the challenges and the opportunities that can accrue from juxtaposing the human aspects, the research and perhaps the financial capabilities of the established, usually northern and western, centers with those of the heavily disease-burdened centers in the South. Already at the first AICI, which was held in 2007, it turned out that this mix, and the reciprocal

PreDicta chip-based high resolution diagnosis of rhinovirus-induced wheeze

Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). The occurrence of numerous RV types is a major challenge for the identification of the culprit virus types and for the improvement of virus type-specific treatment strategies. Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. Importantly, we identify RV-A and RV-C species as giving rise to most severe respiratory symptoms. Thus, we have generated a chip for the serological identification of RV-induced respiratory illness which should be useful for the rational development of preventive and therapeutic strategies targeting the most important RV types.Rhinovirus (RV) infections can trigger acute exacerbations of respiratory diseases. Here, Niespodziana et al. develop a PreDicta chip that identifies the culprit RV strain from small blood samples and show that RV-A and RV-C strains are associated with most severe symptoms.