Center Hospitalier Jean Monnet

Épinal, France

Center Hospitalier Jean Monnet

Épinal, France

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Lupi R.,University of Tuscia | Lupi R.,French National Institute for Agricultural Research | Denery-Papini S.,French National Institute for Agricultural Research | Rogniaux H.,French National Institute for Agricultural Research | And 5 more authors.
Journal of Proteomics | Year: 2013

Wheat kernel albumins/globulins (A/G) and gluten proteins are responsible for baker's asthma and food allergy in atopic subjects. Although no commercial genetically modified wheats are currently being grown, they are under study and the allergenicity of GM products is a major concern.In order to establish the expected and unexpected effects of genetic transformation on allergenicity and also to carry out a safety assessment of genetic transformation, two GM wheat lines (bread and pasta wheat) transformed with endogenous genes were compared to their untransformed counterparts (wt), first by an allergenomic approach, and second, using ELISA with sera from patients suffering from food allergy to wheat and baker's asthma. The 2D immunoblots performed on sera from patients suffering from food allergy and baker's asthma on the A/G fraction of the four lines (two GM and two wt) revealed comparable IgE-binding profiles. A total of 109 IgE-binding spots were analyzed by mass spectrometry, and most of the proteins identified had already been described as allergens or potential allergens. Only two IgE-binding proteins were specific to one GM line. The concentration of specific IgE against the A/G fractions of GM wheat lines and their wt genotypes differed for some sera. Biological significance: The originality of our paper is to relate the transformation of wheat lines with their potential allergenicity using patient sera, such focus has never been done before in wheat and should be of interest to the researches working in this field.Another interesting point of this paper is the study of two types of allergies (respiratory and food) on two wheat genotypes and their GM which reveals that some allergens already known in respiratory allergy could be involved in children suffering from wheat food allergy.In this paper we used a classical 2D proteomic analysis and the protein identifications were performed by mass spectrometry after spot picking and in gel trypsin hydrolysis. Concerning the LC-MS/MS analyses classical software and parameters were used as described in Material and methods. We worked on wheat which is actually not fully sequenced that was a difficulty; we therefore searched against two databanks (proteins and ESTs) in order to compare the results. Moreover all proteins reported in our paper were identified with at least three unique peptides.The identified proteins were checked for their potential allergenicity. In order to have a best interpretation of protein identified in terms of potential allergens, BLAST alignments were performed by using an allergen databank (SDAP). This allows the determination of the cross-reactivity of these identified proteins with known allergens of other species and also the prediction of a potential allergenicity. © 2013.


Denery-Papini S.,French National Institute for Agricultural Research | Bodinier M.,French National Institute for Agricultural Research | Larre C.,French National Institute for Agricultural Research | Brossard C.,French National Institute for Agricultural Research | And 6 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2012

Background Gluten proteins can be modified by deamidation to enhance their solubility and technological applications. However, severe allergic reactions have been reported after the consumption of food products containing deamidated gluten (DG) in subjects tolerant to wheat. This work aimed to characterize allergen profiles for these patients in comparison with those of patients allergic to wheat and to identify IgE-binding epitopes. Methods Sera were obtained from 15 patients allergic to DG and from nine patients allergic to wheat proteins (WP). IgE-binding profiles were characterized both in ELISA and in a humanized rat basophilic leukaemia (RBL) cell model. Epitopes were mapped on γ- and ω2-gliadin sequences by Pepscan, and effect of glutamine/glutamic acid substitutions was studied. Results Compared to the heterogeneous pattern of allergens detected by IgE from patients allergic to WP, responses of patients allergic to DG were homogeneous. In ELISA, all the sera displayed IgE binding to deamidated γ- and ω2-gliadins and deamidated total gliadins, frequently with high concentrations. These modified proteins induced RBL degranulation with most of the sera from DG-allergic patients. A consensus epitope was found on native γ- and ω2-gliadins (QPQQPFPQ); it was repeated several times in their sequences. The substitution of two or three glutamines of this epitope into glutamic acid at positions Q3 or Q4 and Q8 (QPEEPFPE) increased its recognition the best. Conclusion Allergy to DG is a separate entity from wheat allergy. It can be evidenced by strong IgE binding to deamidated gliadins or peptides of the type QPEEPFPE. © 2012 John Wiley & Sons A/S.


Lupi R.,University of Tuscia | Lupi R.,French National Institute for Agricultural Research | Masci S.,University of Tuscia | Rogniaux H.,French National Institute for Agricultural Research | And 6 more authors.
Journal of Cereal Science | Year: 2014

Breeding has enabled the development of wheat genotypes with different quality characteristics and end uses. Despite its numerous positive properties that make it one of the most cultivated crops, wheat is known to induce allergic reactions in predisposed consumers. Genetic modification (GM) technology for crop improvement has recently emerged and its impact on allergenicity must be evaluated, as recommended by the Codex Alimentarius. Our aim was to determine whether the variation in the amount of allergenic polypeptides in five GM wheats, along with their untransformed genotypes, was equivalent to the variation observed among twenty commercial cultivars, either durum or bread wheats. Since the most important factor involved is the amount of allergenic polypeptides, we performed Enzyme-Linked Immunoabsorbent Assays with IgE from twenty-two patients suffering from food or respiratory allergy to wheat on two well characterised soluble protein fractions. Statistical analyses showed a significant effect of the genotypes and sera, both by considering GM lines and untransformed genotypes. This study leads us to conclude that a wide variation exists in the amount of allergenic polypeptides among durum and bread wheat cultivars, and that the differences observed between GM wheats and their parents are within the range of cultivated wheats. © 2014 Elsevier Ltd.


Marelli C.,University Pierre and Marie Curie | Marelli C.,French Institute of Health and Medical Research | Van De Leemput J.,U.S. National Institute on Aging | Van De Leemput J.,University College London | And 22 more authors.
Archives of Neurology | Year: 2011

Background: Deletions in ITPR1, coding for the inositoltriphosphate receptor type 1, have been recently identified in spinocerebellar ataxia type 15 (SCA15). Objective: To determine the frequency and the phenotypical spectrum of SCA15. Design: Taqman polymerase chain reaction (258 index cases) or single-nucleotide polymorphism genomewide genotyping (75 index cases). Setting: A collaboration between the Centre de Recherche de l'Institut de Cerveau et de la Moelle Epinière of the Salpêtrière Hospital (Paris, France) and the Molecular Genetics Unit of the National Institute of Aging (Bethesda, Maryland). Patients: Index cases of 333 families with autosomal dominant cerebellar ataxia negative for CAG repeat expansions in coding exons. Main Outcome Measures: Detection of ITPR1 copy number alterations. Results: A deletion of ITPR1 was found in 6 of 333 families (1.8%), corresponding to 13 patients with SCA15. Age at onset ranged from 18 to 66 years (mean [SD] age, 35 [16] years). The symptom at onset was cerebellar gait ataxia, except in 1 patient with isolated upper limb tremor. Although families were tested irrespective of their phenotype, patients with SCA15 had a homogeneous phenotype and were characterized by a slowly progressive cerebellar ataxia. However, pyramidal signs (2 patients) and mild cognitive problems (2 patients) were occasionally present. Radiologic findings showed global or predominant vermian cerebellar atrophy in all patients. Conclusions: In this series, ITPR1 deletions were rare and accounted for approximately 1% of all autosomal dominant cerebellar ataxias. The SCA15 phenotype mostly consists of a slowly progressive isolated cerebellar ataxia with variable age at onset; an additional pyramidal syndrome and problems in executive functions may be present. ©2011 American Medical Association. All rights reserved.


Thierry G.,Nantes University Hospital Center | Beneteau C.,Nantes University Hospital Center | Pichon O.,Nantes University Hospital Center | Flori E.,Service de Cytogenetique | And 28 more authors.
American Journal of Medical Genetics, Part A | Year: 2012

Patients with a submicroscopic deletion at 1q43q44 present with intellectual disability (ID), microcephaly, craniofacial anomalies, seizures, limb anomalies, and corpus callosum abnormalities. However, the precise relationship between most of deleted genes and the clinical features in these patients still remains unclear. We studied 11 unrelated patients with 1q44 microdeletion. We showed that the deletions occurred de novo in all patients for whom both parents' DNA was available (10/11). All patients presented with moderate to severe ID, seizures and non-specific craniofacial anomalies. By oligoarray-based comparative genomic hybridization (aCGH) covering the 1q44 region at a high resolution, we obtained a critical deleted region containing two coding genes-HNRNPU and FAM36A-and one non-coding gene-NCRNA00201. All three genes were expressed in different normal human tissues, including in human brain, with highest expression levels in the cerebellum. Mutational screening of the HNRNPU and FAM36A genes in 191 patients with unexplained isolated ID did not reveal any deleterious mutations while the NCRNA00201 non-coding gene was not analyzed. Nine of the 11 patients did not present with microcephaly or corpus callosum abnormalities and carried a small deletion containing HNRNPU, FAM36A, and NCRNA00201 but not AKT3 and ZNF238, two centromeric genes. These results suggest that HNRNPU, FAM36A, and NCRNA00201 are not major genes for microcephaly and corpus callosum abnormalities but are good candidates for ID and seizures. © 2012 Wiley Periodicals, Inc.


We are discussing the clinical case of a patient with fibromyalgia syndrome as well as her treatment during a consultation intended to evaluate her chronic pain. Initially, this generalised pain disorder is dealt with in a multidisciplinary way by each professional of the team in order to understand the disorder from a different angle. The different dimensions of pain, i.e., somatic, psychological and social can be better understood as well as the manner in which they are related to each other in the general history of a chronic pain disorder. The evaluation explains the different dimensions of pain, more precisely and effectively, and proposes different strategies for the treatment of chronic pain disorder. As was highlighted in the patient's file, there could be a relation between a very specific phobia and chronic pain syndrome. After evaluating the file, it was then decided to focus on realistic objectives in agreement with the patient after a more detailed psychometric evaluation. Cognitive and behavioural therapy treatment is integrated in a therapeutic plan including medication with the pursuit of physical therapy and planned rehabilitation. In addition, there is the option of complementary techniques such as relaxation and hypnotherapy. © 2010 Elsevier Masson SAS. All rights reserved.


Herin F.,Nancy University Hospital Center | Poussel M.,Nancy University Hospital Center | Renaudin J.-M.,Center Hospitalier Jean Monnet | Leininger A.,Nancy University Hospital Center | And 3 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2012

The present case study reports the first case of a 38-yearold hairdresser with irritant-associated vocal cord dysfunction (VCD) due to alkaline persulfate, who was referred on suspicion of occupational asthma. Several tests were performed, including specific inhalation challenge and upper airway endoscopy. During the specific inhalation challenge to alkaline persulfate, the patient experienced dysphonia and a non-significant decrease in forced expiratory volume in 1 second on spirometry. Upper airway endoscopy was then performed and revealed VCD. A specific inhalation challenge test is therefore essential in cases of VCD to exclude possible concomitant occupational asthma. © 2012 The Union.


Renaudin J.-M.,Center hospitalier Jean Monnet
Revue Francaise d'Allergologie | Year: 2011

Recent literature about occupational asthma or rhinitis is proposing new classifications of these diseases, and describes current strategy for diagnosis and for preventing. Some papers describe new allergens, as well as detailing the advances in molecular biology. It allows better identification of occupational IgE-mediated hypersensitivities. © 2011 Elsevier Masson SAS.


Exercise-induced anaphylaxis is defined as the onset of allergic symptoms during, or immediately after exercise, the clinical signs being various degrees of urticaria, angioedema, respiratory and gastrointestinal signs, and sometimes anaphylactic shock. Food-dependent exercise-induced anaphylaxis (FDEIA) introduces food as a factor in the syndrome and follows a particular chronological sequence: food intake is followed, after a variable interval, by exercise, during the course of which the clinical signs of FDEIA appear. When the food intake and the exercise are independent of each other, no symptoms occur. FDEIA occurs infrequently. Identification of the responsible food depends on the patient's eating habits. Seafood and wheat flour are the two commonest causes. Once the allergen has been identified, it should not be eaten for at least four to five hours before any exercise. © 2010 Elsevier Masson SAS. All rights reserved.


Renaudin J.-M.,Center hospitalier Jean Monnet
Revue Francaise d'Allergologie | Year: 2010

Insect stings may cause anaphylactic reactions at the workplace or during working hours. Epidemiologic studies of Hymenoptera venom hypersensitivity specifically of occupational origin or of asthma induced by stinging insects are limited. There are few reports on the occupational outcome of these allergies. © 2010 Elsevier Masson SAS. All rights reserved.

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