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Transformative results of adeno-associated virus (AAV) gene therapy in patients with spinal muscular atrophy and Leber’s congenital amaurosis led to approval of the first two AAV products in the United States to treat these diseases. These extraordinary results led to a dramatic increase in the number and type of AAV gene-therapy programs. However, the field lacks non-invasive means to assess levels and duration of therapeutic protein function in patients. Here, we describe a new magnetic resonance imaging (MRI) technology for real-time reporting of gene-therapy products in the living animal in the form of an MRI probe that is activated in the presence of therapeutic protein expression. For the first time, we show reliable tracking of enzyme expression after a now in-human clinical trial AAV gene therapy (ClinicalTrials.gov: NTC03952637) encoding lysosomal acid beta-galactosidase (βgal) using a self-immolative βgal-responsive MRI probe. MRI enhancement in AAV-treated enzyme-deficient mice (GLB-1−/−) correlates with βgal activity in central nervous system and peripheral organs after intracranial or intravenous AAV gene therapy, respectively. With >1,800 gene therapies in phase I/II clinical trials (ClinicalTrials.gov), development of a non-invasive method to track gene expression over time in patients is crucial to the future of the gene-therapy field., Graphical abstract, We describe a bio-responsive contrast agent that informs on the biodistribution and durability of gene expression in the lysosomal storage disease, GM1 gangliosidosis. We illustrate the sensitivity of this contrast agent to detect β-galactosidase enzyme in the central nervous system and periphery of an AAV-GLB-1-treated mouse model of GM1.

GM1 gangliosidosis (GM1) is a fatal neurodegenerative lysosomal storage disease that occurs most commonly in young children, with no effective treatment available. Long-term follow-up of GM1 cats treated by bilateral thalamic and deep cerebellar nuclei (DCN) injection of adeno-associated virus (AAV)-mediated gene therapy has increased lifespan to 8 years of age, compared with an untreated lifespan of ~8 months. Due to risks associated with cerebellar injection in humans, the lateral ventricle was tested as a replacement route to deliver an AAVrh8 vector expressing feline β-galactosidase (β-gal), the defective enzyme in GM1. Treatment via the thalamus and lateral ventricle corrected storage, myelination, astrogliosis, and neuronal morphology in areas where β-gal was effectively delivered. Oligodendrocyte number increased, but only in areas where myelination was corrected. Reduced AAV and β-gal distribution were noted in the cerebellum with subsequent increases in storage, demyelination, astrogliosis, and neuronal degeneration. These postmortem findings were correlated with endpoint MRI and magnetic resonance spectroscopy (MRS). Compared with the moderate dose with which most cats were treated, a higher AAV dose produced superior survival, currently 6.5 years. Thus, MRI and MRS can predict therapeutic efficacy of AAV gene therapy and non-invasively monitor cellular events within the GM1 brain.

Osteoporosis is characterized by a loss of bone mass along with alterations in its structure, with subsequent increase in bone fragility and susceptibility to fractures, ultimately reinforcing the importance of its prevention by the reduction of the risk of falling.

Tay-Sachs Disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Preclinical work demonstrated safety and efficacy of CNS gene therapy using AAVrh8-HEXA/HEXB. Here we describe an expanded access trial in two patients with infantile TSD (IND 18225). Case TSD-001 demonstrated neurodevelopmental regression by 8 months of age and severe seizures by 1 year was treated at 30 months. An equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB (now AXO-AAV-GM2) was administered intrathecally (IT), with 75% of the dose (1x1014vg) delivered to the cisterna magna and 25% at the thoraco-lumbar junction. The second patient (TSD-002) was treated at 7 months of age with 4.2x1013 vg by a combination of bilateral thalamic (0.18 mL; 1.5x1012vg per thalamus), and IT infusion (3.9x1013vg). Both patients underwent immunosuppression with sirolimus, corticosteroids, and rituximab. Injection procedures were well tolerated and have shown no vector-related adverse events to date. CSF HexA activity nearly doubled from baseline and remained stable. In TSD-002 (now 16 months of age), MRI showed stabilization of disease by 3 months post-injection and appeared to temporarily deviate from the natural history of infantile TSD but declined again 6 months post-treatment. TSD-001 (now 4.5 years of age remains seizure-free on the same anti-convulsant therapy as pre-therapy, but TSD-002 developed seizures between 13 and 17 months posttreatment (by 2 years of age). Administration of AXO-AAV-GM2 by IT and thalamic injections was safe, HexA activity increased in CSF and ongoing myelination was apparent in the younger patient treated at an early symptomatic stage. This study provides early safety and proof-of-concept in humans for treatment of TSD patients by AAV gene therapy.

GM1 gangliosidosis is a fatal neurodegenerative disease caused by a deficiency of lysosomal β-galactosidase. In its most severe form, GM1 gangliosidosis causes death by 4 years of age, and no effective treatments exist. Previous work has shown that injection of the brain parenchyma with an adeno-associated viral (AAV) vector provides pronounced therapeutic benefit in a feline GM1 model. To develop a less invasive treatment for the brain and increase systemic biodistribution, intravenous injection of AAV9 was evaluated. AAV9 expressing feline β-galactosidase was intravenously administered at 1.5×1013 vector genomes/kg body weight to six GM1 cats at ∼1 month of age. The animals were divided into two cohorts: (i) a long-term group, which was followed to humane end point; and (ii) a short-term group, which was analysed 16 weeks post-treatment. Clinical assessments included neurological exams, CSF and urine biomarkers, and 7 T MRI and magentic resonance spectroscopy (MRS). Post-mortem analysis included β-galactosidase and virus distribution, histological analysis and ganglioside content. Untreated GM1 animals survived 8.0 ± 0.6 months while intravenous treatment increased survival to an average of 3.5 years (n = 2) with substantial improvements in quality of life and neurological function. Neurological abnormalities, which in untreated animals progress to the inability to stand and debilitating neurological disease by 8 months of age, were mild in all treated animals. CSF biomarkers were normalized, indicating decreased CNS cell damage in the treated animals. Urinary glycosaminoglycans decreased to normal levels in the long-term cohort. MRI and MRS showed partial preservation of the brain in treated animals, which was supported by post-mortem histological evaluation. β-Galactosidase activity was increased throughout the CNS, reaching carrier levels in much of the cerebrum and normal levels in the cerebellum, spinal cord and CSF. Ganglioside accumulation was significantly reduced by treatment. Peripheral tissues such as heart, skeletal muscle, and sciatic nerve also had normal β-galactosidase activity in treated GM1 cats. GM1 histopathology was largely corrected with treatment. There was no evidence of tumorigenesis or toxicity. Restoration of β-galactosidase activity in the CNS and peripheral organs by intravenous gene therapy led to profound increases in lifespan and quality of life in GM1 cats. These data support the promise of intravenous gene therapy as a safe, effective treatment for GM1 gangliosidosis.

The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are fatal lysosomal storage disorders caused by mutations in the HEXA and HEXB genes, respectively. These mutations cause dysfunction of the lysosomal enzyme β-N-acetylhexosaminidase A (HexA) and accumulation of GM2 ganglioside (GM2) with ensuing neurodegeneration, and death by 5 years of age. Until recently, the most successful therapy was achieved by intracranial co-delivery of monocistronic adeno-associated viral (AAV) vectors encoding Hex alpha and beta-subunits in animal models of SD. The blood-brain barrier crossing properties of AAV9 enables systemic gene therapy; however, the requirement of co-delivery of two monocistronic AAV vectors to overexpress the heterodimeric HexA protein has prevented the use of this approach. To address this need, we developed multiple AAV constructs encoding simultaneously HEXA and HEXB using AAV9 and AAV-PHP.B and tested their therapeutic efficacy in 4- to 6-week-old SD mice after systemic administration. Survival and biochemical outcomes revealed superiority of the AAV vector design using a bidirectional CBA promoter with equivalent dose-dependent outcomes for both capsids. AAV-treated mice performed normally in tests of motor function, CNS GM2 ganglioside levels were significantly reduced, and survival increased by >4-fold with some animals surviving past 2 years of age.

Global gene delivery to the CNS has therapeutic importance for the treatment of neurological disorders that affect the entire CNS. Due to direct contact with the CNS, cerebrospinal fluid (CSF) is an attractive route for CNS gene delivery. A safe and effective route to achieve global gene distribution in the CNS is needed, and administration of genes through the cisterna magna (CM) via a suboccipital puncture results in broad distribution in the brain and spinal cord. However, translation of this technique to clinical practice is challenging due to the risk of serious and potentially fatal complications in patients. Herein, we report development of a gene therapy delivery method to the CM through adaptation of an intravascular microcatheter, which can be safely navigated intrathecally under fluoroscopic guidance. We examined the safety, reproducibility, and distribution/transduction of this method in sheep using a self-complementary adeno-associated virus 9 (scAAV9)-GFP vector. This technique was used to treat two Tay-Sachs disease patients (30 months old and 7 months old) with AAV gene therapy. No adverse effects were observed during infusion or post-treatment. This delivery technique is a safe and minimally invasive alternative to direct infusion into the CM, achieving broad distribution of AAV gene transfer to the CNS.

Background Pharmacy-based interventions are complex public health endeavors which include, but are not restricted to, the conventional medication supply role. In diabetes, such interventions may improve patients’ outcomes. The aim of this study was to review relevant policies and research developed in Portugal directed at pharmacy-based diabetes interventions, and to inform future policies, practice and research in collaborative practice with primary care. Research method An exploratory review of diabetes legislation and policy papers, as well as a comprehensive review in Embase, MEDLINE (via Ovid and PubMed), Google Scholar, and grey literature until November 2017 was performed. Results Sixteen policy papers and 10 studies were included in the analysis. Positive evidence from pharmacy interventions was retrieved concerning screening individuals at risk, screening uncontrolled patients, managing diabetes, and supporting self-monitoring. Conclusions Some consistency in favorable findings, but also room for improvements in health policies, intervention design and research methods, were observed. Electronic supplementary material The online version of this article (10.1186/s40545-019-0166-1) contains supplementary material, which is available to authorized users.

A aprovação das plantas geneticamente modificadas é precedida de vários anos de investigação intensiva de forma a garantir a sua segurança para o homem e ambiente. Recentemente demonstrámos que o stress da cultura in vitro parece ser o fator que mais influencia as diferenças proteómicas encontradas entre as plantas geneticamente modificadas (GM) e os seus controlos. Neste trabalho tentámos avaliar quantas gerações são necessárias para os efeitos da “memória” desse stress serem apagados. Tentámos também comparar a relevância das alterações provocadas pelo stress da cultura in vitro quando comparadas com as provocadas por outros stresses ambientais. Para tal seguimos três linhas de arroz durante oito gerações após a transgénese combinando técnicas de análise transcritómica e proteómica. Na geração F6 as plantas foram sujeitas a stress salino. Os resultados deste trabalho demonstraram que: (a) as diferenças promovidas durante a modificação genética são maioritariamente diferenças fisiológicas de curta duração, que atenuam ao longo do tempo; (b) os stresses ambientais podem causar mais alterações proteómicas/trascritómicas que a engenharia genética. Com base nos dados obtidos questionamos quais os ensaios que são realmente relevantes e quais aqueles claramente excessivos na avaliação do risco das plantas GM para a saúde humana e animal, plantas e ambiente. The approval of genetically modified (GM) crops is preceded by years of intensive research to demonstrate safety to humans and environment. We recently showed that in vitro culture stress is the major factor influencing proteomic dif ferences of GM vs. non-GM plants. This made us question the number of generations needed to erase such "memor y". We also wondered about the relevance of alterations promoted by transgenesis as compared to environment-induced ones. Here we followed three rice lines throughout eight generations af ter transgenesis combining proteomics and transcriptomics, and fur ther analyzed their response to salinity stress on the F6 generation. Our results showed that: (a) dif ferences promoted during genetic modification are mainly shor t-term physiological changes, attenuating throughout generations, and (b) environmental stress may cause far more proteomic/transcriptomic alterations than transgenesis. Based on our data, we question what is really relevant in risk assessment design for GM food crops. info:eu-repo/semantics/publishedVersion

O artigo foi elaborado a partir do estudo dos resultados de duas dissertações de mestrado (Estudo 1 e 2) e de uma tese de doutorado (Estudo 3). Foram identificadas reações emocionais comuns e freqüentes nos portadores de diabetes mellitus (DM), que comprometem o desempenho dos papéis de autocuidado. Teve como objetivos: apresentar as reações emocionais identificadas em portadores de DM tipo 1 e 2 e discutir as interferências das reações emocionais para desempenho dos papéis de autocuidado. Dos resultados, emergiram as categorias de reações emocionais: medo, raiva/ revolta, tristeza, depressão e estresse/ansiedade. Evidenciou-se ser a DM uma doença que, independente do tipo e da faixa etária, causa um impacto negativo biopsicossocial. Concluiu-se que há necessidade de uma abordagem mais ampla para a relação entre as reações emocionais e o desempenho das ações de autocuidado dos portadores de DM. The article was elaborated based on the study of the two thesis master of degrees (Study 1 and 2) and of a doctorate thesis (Study 3). Had been identified reactions emotional common and frequency in the patients with Diabetes Mellitus (DM), being able to compromise the action performance of papers of self-care. We have as objective: to present reactions emotional identified in patients with DM they intervene with the action performance of papers of self-care and arguing the emotional the interferences of for the self-care. Of the results the emotional categories of reactions had emerged: fear; anger, bad behavior, depressive feelings and stress/ anxiety. Evidencing to be independent DM an illness of the type and the age band it is the cause of a biopsychosocial negative impact. It is concluded the necessity of a larger approaching related to the emotional reaction and the action performance of self-care roles of patients with DM. El artículo fue elaborado basó en el estudio del año de dos tesis de bachillerato (estudio 1 y 2) y de una tesis del doctorado (el estudio 3). Habían sido el campo común y la frecuencia emocionales identificados de las reacciones en los pacientes con la Diabetes Mellitus (DM), pudiendo comprometer el funcionamiento de la acción de papeles del auto-cuidado. Tenemos como objetivo: para presentar a reacciones emocional identificado en pacientes con DM que él interviene con el funcionamiento de la acción de papeles del autocuidado y de discutir las interferencias para el uno mismo-cuidado. De los resultados las categorías emocionales de reacciones habían emergido: miedo; cólera, mal comportamiento, depresiva stress/ ansiedad . El evidenciar a ser la independiente DM a la enfermedad del tipo y la edad causa un impacto negativo biopsicosocial. Se concluí la necesidad de un amplio estudio para la relación entre las reacciones emocionales y el funcionamiento de la acción de papeles del auto-cuidado en pacientes con el DM.

Primary central nervous system tumours represent the second most frequent neoplasm and are the leading cause of death from solid tumours in children. Our study aimed to provide the most up-to-date epidemiological analysis of primary central nervous system tumours in children living in the north of Portugal and to explore a possible effect of the centralisation of care on outcomes.This population-based study included all newly diagnosed and histologically confirmed primary central nervous system tumours in people below 18 years old, living in the north of Portugal, from January 2008 to December 2013. Data were collected through access to clinical files. We described children and tumour characteristics, and analysed patient: paediatric neurosurgeon and histological tumour type: paediatric neurosurgeon ratios.A total of 147 cases was recorded. Mean age at diagnosis of primary central nervous system tumours was 8.0 ± 5.2 years. Astrocytomas were the most common histological type (34%). We found that World Health Organization Tumour Grade was the only variable of statistically significant influence in mortality (p = 0.001). 1-, 3- and 5-year survivals related to 2008-2013 period were statistically higher than 2005 - 2007. Astrocytomas have the highest survival rate, with statistically significant difference from other tumours (p = 0.015). We estimated a mean of 12.25 treated cases per year by each paediatric neurosurgeon at our institution.Our results are globally consistent with those published all over the world, but we reported the highest survival rates. The number of cases treated per year by each neurosurgeon is accordant to the recommended.We showed an improvement when comparing to data previous to 2008 and better results than those from previous studies, namely higher survival at 1-, 3- and 5-years from the diagnosis, with low complication and relapsing rates. Therefore, the referral of primary central nervous system tumours cases to centres with larger experience can be invaluable for the achievement of the best outcomes.Introdução: Os tumores primários do sistema nervoso central representam o segundo grupo de neoplasias mais frequente e são a principal causa de morte devido a tumores sólidos em crianças. O nosso estudo teve como objetivos realizar a mais atualizada análise epidemiológica desta doença no norte de Portugal e avaliar o possível benefício da centralização de cuidados. Material e Métodos: Este estudo de base populacional incluiu todos os tumores primários do sistema nervoso central diagnosticados e histologicamente confirmados em indivíduos menores de 18 anos de idade, que residem no norte do país, desde Janeiro 2008 até Dezembro 2013. Os dados foram obtidos por meio da avaliação dos processos clínicos dos doentes. Nós descrevemos as características das crianças e dos seus tumores e analisámos os quocientes doente: neurocirurgião pediátrico e tipo histológico de tumor: neurocirurgião pediátrico e as taxas de sobrevivência, mortalidade, complicações e recidiva. Resultados: Foram registados 147 casos. A média de idade ao diagnóstico foi de 8,0 ± 5,2 anos. Os astrocitomas foram o tipo histológico mais frequentemente encontrado (34%). O tipo histológico foi a única variável com influência estatisticamente significativa na mortalidade (p = 0,001). As sobrevivências a um, três e cinco anos relativas ao período entre 2008 - 2013 foram estatisticamente superiores às do intervalo entre 2005 - 2007. Os astrocitomas apresentam a mais alta taxa de sobrevivência, sendo estatisticamente diferente dos outros tipos de tumor (p = 0,015). Estimámos uma média de 12,25 casos tratados anualmente por neurocirurgião pediátrico no nosso hospital. Discussão: Os nossos resultados são, globalmente, consistentes com os encontrados na literatura mundial, mas registrámos taxas de sobrevivência mais altas. O número de casos tratados por neurocirurgião pediátrico está de acordo com o recomendado. Conclusão: Demonstrámos que houve melhoria dos outcomes em estudo em relação aos obtidos previamente a 2008 e aos reportados por outros estudos, nomeadamente taxas de sobrevivência a um, três e cinco anos após o diagnóstico mais elevadas, com índices de complicações e recidiva baixos. Neste sentido, a referenciação destes casos para centros de vasta experiência pode ser de valor inestimável para se obter os melhores resultados.

Plant breeders need new and more precise tools to accelerate breeding programs that address the increasing needs for food, feed, energy and raw materials, while facing a changing environment in which high salinity and drought have major impacts on crop losses worldwide. This review covers the achievements and bottlenecks in the identification and validation of proteins with relevance in abiotic stress tolerance, also mentioning the unexpected consequences of the stress in allergen expression. While addressing the key pathways regulating abiotic stress plant adaptation, comprehensive data is presented on the proteins confirmed as relevant to confer tolerance. Promising candidates still to be confirmed are also highlighted, as well as the specific protein families and protein modifications for which detection and characterization is still a challenge. This article is part of a Special Issue entitled: Translational Plant Proteomics.

Before market introduction, genetic engineered (GE) food products, like any other novel food product, are subjected to extensive assessment of their potential effects on human health. In recent years, a number of profiling technologies have been explored aiming to increase the probability of detecting any unpredictable unintended effect and, consequently improving the efficiency of GE food safety assessment. These techniques still present limitations associated with the interpretation of the observed differences with respect to their biological relevance and toxicological significance. In order to address this issue, in this study, we have performed 2D-gel electrophoresis of five different ears of five different MON810 maize plants and of other five of the non-transgenic near-isogenic line. We have also performed 2D-gel electrophoresis of the pool of the five protein extractions of MON810 and control lines. We have notice that, in this example, the exclusive use of data from 2D-electrophoresed pooled samples, to compare these two lines, would be insufficient for an adequate safety evaluation. We conclude that, when using ‘‘omics” technologies, it is extremely important to eliminate all potential differences due to factors not related to the ones under study, and to understand the role of natural plant-to-plant variability in the encountered differences.

The generation of genetically engineered (GE) foods has been raising several concerns and controversies that divide not only the general public but also the scientific community. The fear and importance of the new technology, as well as commercial interests, have supported many of the ongoing discussions. The recent increase in the number of GE foods approved for import into the European Union and the increasingly global commercial food trades justify revisiting the facts and fiction surrounding this technology with the aim of increasing public awareness for well-informed decisions. Techniques that have recently become available for assessing food quality and its impact on human health, as well as the wealth of scientific data previously generated, clearly support the safety of commercialized GE products.

Este estudo tem como objetivos analisar as publicações científicas e técnicas sobre os procedimentos de precauções-padrão em periódicos nacionais e internacionais e destacar aspectos importantes dos artigos no que se refere ao papel da enfermeira na prevenção e controle da infecção hospitalar. Constituíram como amostra da pesquisa as fontes secundárias em forma de livros e periódicos, com a finalidade de nos colocar em contato direto com os artigos levantados sobre o uso das precauções-padrão para as infecções hospitalares na assistência de enfermagem, entre 1999 e 2005. Foram encontrados 10 artigos relacionados ao uso de precauções-padrão: 70% foram obtidos em Banco de Teses, 20%, no site Scielo e 10%, na biblioteca de uma universidade pública do Rio de Janeiro, sendo 40% publicados no ano de 2003. Os resultados mostraram que, neste período, apesar de poucas publicações, houve uma contínua renovação do tema, tanto a nível nacional, quanto internacional. This study has as objectives, analyze the scientific and technical publications about the standard procedures of precautions in national and international newspapers and to highlight important aspects of articles about the nurse's paper in the prevention and control of hospital infection. It constituted as sample of the research the secondary sources in form of books and newspaper, with the purpose of putting us in direct contact with articles raised about the use of the precautions standard for the hospital infections in the nursing care, between 1999 and 2005. 10 articles related to the use of standard precautions had been found: 70% had been gotten in Bank of Teses, 20% in the site Scielo and 10% in the library of a public university of Rio de Janeiro, being 40% published in the year of 2003. The results showed that, in this period, in spite of few publications, there was a continuous renewal of the theme, such as national level, as international. Este estudio tiene como objetivos analizar las publicaciones científicas y técnicas, que los procedimientos de las precauciones estándares en periódicos nacionales e internacionales, separar aspectos importantes de artículos acerca del papel de la enfermera en la prevención y controlar la infección en hospital. Ellos constituirán como proba, los orígenes secundarios en la forma de libros y periódicos de la investigación, con el propósito de ponernos en contacto directo con los artículos en el uso de las precauciones estándares para las infecciones del hospital en la atención de enfermería, entre 1999 y 2005 con el uso de las precauciones. 10 artículos se relacionaron con el uso de precauciones habían sido encontrado: 70% habían sido conseguidos en Banco de Teses, el 20% en el sitio Scielo y el 10% en la biblioteca de una universidad pública de Río de Janeiro, siendo 40% publicado en el año de 2003. Los resultados mostraban que, en este período, a pesar de pocas publicaciones, había una renovación continua del tema, tanto en el nivel nacional, como internacional.

Background: The safety issues regarding foods derived from genetically modified (GM) plants are central to their acceptance into the food supply. The potential allergenicity of proteins newly introduced in GM foods is a major safety concern. Objective: We sought to monitor, in potentially sensitive human populations, the allergenicity effects of 5 GM materials obtained from sources with no allergenic potential and already under commercialization in the European Union. Methods: We have performed skin prick tests with protein extracts prepared from transgenic maize (MON810, Bt11, T25, Bt176) and soya (Roundup Ready) samples and from nontransgenic control samples in 2 sensitive groups: children with food and inhalant allergy and individuals with asthmarhinitis. We have also tested IgE immunoblot reactivity of sera from patients with food allergy to soya (Roundup Ready) and maize (MON810, Bt11, Bt176) samples, as well as to the pure transgenic proteins (CryIA[b] and CP4 5-enolpyruvylshikimate- 3-phosphate synthase). Results: None of the individuals undergoing tests reacted differentially to the transgenic and nontransgenic samples under study. None of the volunteers tested presented detectable IgE antibodies against pure transgenic proteins. Conclusion: The transgenic products under testing seem to be safe in terms of allergenic potential. We propose postmarket testing as an important screening strategy for putative allergic sensitization to proteins introduced in transgenic plants. Supported by Fundação Calouste Gulbenkian, research project SDH.SP.I.01.11 and by Comissão de Fomento da Investigação em Cuidados de Saúde, research project no. 186/01

Background: Allergies are nearly always triggered by protein molecules and the majority of individuals with documented immunologic reactions to foods exhibit IgE hypersensitivity reactions. In this study we aimed to understand if natural differences, at proteomic level, between maize populations, may induce different IgE binding proteins profiles among maize-allergic individuals. We also intended to deepen our knowledge on maize IgE binding proteins. Results: In order to accomplish this goal we have used proteomic tools (SDS-PAGE and 2-D gel electrophoresis followed by western blot) and tested plasma IgE reactivity from four maize-allergic individuals against four different protein fractions (albumins, globulins, glutelins and prolamins) of three different maize cultivars. We have observed that maize cultivars have different proteomes that result in different IgE binding proteins profiles when tested against plasma from maize-allergic individuals. We could identify 19 different maize IgE binding proteins, 11 of which were unknown to date. Moreover, we found that most (89.5%) of the 19 identified potential maize allergens could be related to plant stress. Conclusions: These results lead us to conclude that, within each species, plant allergenic potential varies with genotype. Moreover, considering the stress-related IgE binding proteins identified, we hypothesise that the environment, particularly stress conditions, may alter IgE binding protein profiles of plant components.