Impact of an adaptive program for cognitive and emotional deficits (ADACOG program) in multiple sclerosis patients with cognitive impairments.

BACKGROUND: Cognitive impairment is frequent in multiple sclerosis (MS), affecting approximately 40 to 70% of patients. We developed a psycho-educational program (ADACOG program) to allow patients to cope with cognitive deficits. The purpose of this exploratory study was to investigate the impact of the ADACOG program on subjective self-reported cognitive impairments, quality of life, anxiety, depression and self-esteem in MS patients. METHODS: ADACOG program is a psycho-educational program focusing on cognitive and emotional dysfunctions in MS consisting of three modules in small groups lasting two hours every two weeks. Forty-five MS patients with self-reported cognitive impairments and objective cognitive deficits were enrolled consecutively in two groups: (i) the ADACOG group (N=24) and (ii) the control group (N=21). Both groups of patients completed questionnaires evaluating self-reported cognitive impairments (Multiple Sclerosis Neuropsychological Screening Questionnaire), quality of life (Multiple Sclerosis Impact Scale), anxiety and depression (Hospital Anxiety and Depression Scale, HAD) and self-esteem (Rosenberg Scale) at inclusion (M0), one month later (M1) and seven months after inclusion (M7). The evolution of outcomes within ADACOG group and between both groups was analyzed. RESULTS: The analyses within the ADACOG group showed that patients reported better quality of life and fewer anxiety symptoms at M1 compared to M0 (respectively P=0.03 and P=0,04). Moreover, patients presented less subjective self-reported cognitive deficits at M7 compared to M0 (P=0.003). Score evolution for HAD depression and self-esteem were not significant within the ADACOG group. The change M1-M0 for MSIS-29 and HAD anxiety scores was significantly different between both groups (respectively P=0.04 and P=0.008), with improvement of quality of life and anxiety in the ADACOG group. The evolution of scores between groups was not significant for the other outcomes. DISCUSSION: This study showed a small effect of a psycho-educational program focusing on cognitive and emotional disorders in MS patients with subjective self-reported cognitive deficits and objective cognitive deficits. Interest of psycho-education focusing on cognition in MS patients is discussed.

French consensus procedure for assessing cognitive function in Parkinson's disease.

INTRODUCTION: One of the objectives of the French expert centers for Parkinson's disease (NS-Park) network was to determine a consensus procedure for assessing cognitive function in patients with Parkinson's. This article presents this procedure and briefly describes the selected tests. METHODS: A group of 13 experts used the Delphi method for consensus building to define the overall structure and components of the assessment procedure. For inclusion in the battery, tests had to be validated in the French language, require little motor participation, have normative data and be recognized by the international community. Experimental tasks and tests requiring specific devices were excluded. RESULTS: Two possibilities were identified, depending on whether an abbreviated or comprehensive assessment of cognitive function was necessary. For an abbreviated assessment, the experts recommended the Montreal Cognitive Assessment (MoCA) as a screening test for cognitive impairment or dementia. For a comprehensive neuropsychological assessment, the experts recommended assessing global efficiency plus the five main cognitive domains (attention and working memory, executive function, episodic memory, visuospatial function and language) that may be impaired in Parkinson's disease, using two tests for each domain. DISCUSSION AND CONCLUSION: A common procedure for assessing cognitive function is now available across the French network dedicated to Parkinson's disease, and is recommended for both research and clinical practice. It will also help to promote standardization of the neuropsychological assessment of Parkinson's disease.

Allergy to deamidated gluten in patients tolerant to wheat: specific epitopes linked to deamidation.

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.

Immunoglobulin-E-binding epitopes of wheat allergens in patients with food allergy to wheat and in mice experimentally sensitized to wheat proteins.

BACKGROUND: At present, B cell epitopes involved in food allergy to wheat are known only for a few allergens and a few categories of patients. OBJECTIVE: To characterize the epitopes of different wheat kernel allergens: α-, γ, ω2, and ω5-gliadin, a low-molecular-weight (LMW) glutenin subunit, and a lipid transfer protein (LTP1) recognized by allergic patients and by sensitized mice and provide further understanding of the role of structure in determining allergic response. METHODS: Sera were obtained from 39 patients suffering from food allergy to wheat. BALB/c mice were sensitized to gliadins or LTP1 by intraperitoneal immunizations. Continuous epitopes bound by IgE were delineated by the Pepscan technique. The response to reduced, alkylated LTP1 was compared with that of the native form to evaluate the importance of protein folding on IgE reactivity. RESULTS: Few continuous epitopes of LTP1 reacted with IgE from allergic patients and mice, but one of them was common to several patients and sensitized mice. The unfolded protein was not recognized by either patient or mouse IgE, emphasizing the major role of LTP1 folding and discontinuous epitopes in IgE-binding. In contrast, many continuous epitopes were detected by patient and mouse IgE especially for an ω5-gliadin, which is an unstructured protein, and to a lesser extent, for the other gliadins and a LMW-glutenin subunit. CONCLUSION AND CLINICAL RELEVANCE: The conformation of LTP1 appeared to have a strong impact on the type of IgE-binding epitopes elicited by this protein in both man and mouse. The responses in mice sensitized to gliadins or LTP1 were sufficiently comparable with the human response in terms of IgE-binding epitopes to provide support for the use of the mouse model in further investigations.

Evaluation of an in vitro mast cell degranulation test in the context of food allergy to wheat.

BACKGROUND: Antigenic profiles obtained by ELISA with IgE from patients with wheat food allergy (WFA) established that major allergens are albumins/globulins (AG) for children suffering from atopic eczema/dermatitis syndrome (AEDS), omega5-gliadins for adults suffering from wheat-dependent exercise-induced anaphylaxis (WDEIA), anaphylaxis or urticaria and low-molecular-weight (LMW) glutenin subunits for patients with anaphylaxis. We aimed to characterize a new mast cell transfectant for its ability to degranulate with wheat proteins and patient sera and compare these results to those obtained by ELISA. METHODS: Thirty sera from patients with WFA were tested: 14 with AEDS (group 1) and 16 with WDEIA, anaphylaxis or urticaria (group 2). An IgE Fc receptor (FcepsilonRI) humanized rat RBL-2H3 line was established by transfection with cDNAs encoding alpha-, beta- and gamma-subunits for the human IgE receptor. RESULTS: A humanized RBL clone was selected for its capacity to express mRNA alpha-, beta- and gamma-subunits of FcepsilonRI, to bind allergen-specific human IgE and to degranulate. In group 1, sera induced enhanced degranulation with AG extract, but rarely reacted with gliadins and glutenins. In group 2, half of the sera showed degranulation with LMW glutenins whereas the AG fraction and lipid transfer proteins were rarely positive. omega5-Gliadins did not appear as a major allergen in degranulation assays, although functional allergen-specific IgE was measurable in appreciable amounts. CONCLUSION: Our data demonstrate that in wheat food allergen evaluation, correlation exists between mast cell degranulation and IgE measurements, depending on the type of allergen. Therefore, the biological activity of some allergen types may also be affected by other parameters.

Identification of IgE-binding epitopes on gliadins for patients with food allergy to wheat.

BACKGROUND: Food allergy to wheat induces different symptoms as atopic eczema/dermatitis syndrome (AEDS), urticaria and more severe reactions as wheat-dependent exercise-induced anaphylaxis (WDEIA). Different gliadin classes are involved in this allergy but IgE-binding epitopes are known only on omega5-gliadins and for WDEIA cases. OBJECTIVES: The aim of the study was to identify IgE-binding epitopes on several gliadin classes and for several patients with different symptoms and ages. METHODS: Eleven sera were analysed by pepscan with overlapping synthetic peptides. RESULTS: Sera from five patients with anaphylaxis, urticaria or WDEIA, displayed strong IgE-binding to sequential epitopes of the repetitive domains of alphabeta, gamma, omega2 or omega5-gliadins with two immunodominant epitopes on omega5-gliadin and a consensus motif of the type QQX1PX2QQ (X1 being L, F, S or I and X2 Q, E or G). One patient allergic to deamidated wheat proteins also had IgE to a repetitive peptide of gamma and omega2-gliadins of the type QPQQPFP. Sera from four patients with AEDS detected no linear epitopes on gliadins, despite the fact that they contained specific IgE to alpha, beta, gamma or omega-gliadins. One child with AEDS recognized cysteine-containing sequences in the nonrepetitive domains of alphabeta and gamma-gliadins. CONCLUSION: B epitopes in wheat allergy were different from B epitopes of coeliac disease. Differences exist in IgE-binding epitopes between patients with food allergy to wheat. IgE from those suffering from WDEIA, anaphylaxis and urticaria detected sequential epitopes in the repetitive domain of gliadins whereas IgE from AEDS patients probably recognized conformational epitopes.

Food allergy to wheat: identification of immunogloglin E and immunoglobulin G-binding proteins with sequential extracts and purified proteins from wheat flour.

BACKGROUND: Cereal-associated allergy is particularly considered a serious problem, because cereals are essential in our daily diet. Wheat proteins are classified into albumins, globulins and prolamins (insoluble gliadins and glutenins). OBJECTIVES: Our objectives were to study the involvement in food allergy to wheat of these different protein types by using purified fractions and to identify those binding IgE and IgG antibodies. METHODS: Sera were obtained from 28 patients with food allergy to wheat. Albumins/globulins, gliadins and glutenins were obtained by sequential extraction based on differential solubility; alpha-, beta-, gamma- and omega-gliadins and low molecular weight (LMW) and high molecular weight (HMW) glutenin subunits were purified by chromatography. IgE binding to these extracts and fractions were analysed by radioallergosorbent test (RAST), and immunoblotting; IgG binding was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: In RAST, 60% of sera were shown to have specific IgE antibodies against alpha-, beta-gliadins and LMW glutenin subunits, 55% to gamma-gliadins, 48% to omega-gliadins and 26% to HMW glutenins. Immunoblotting analysis confirmed results obtained in RAST concerning LMW and HMW glutenin subunits and showed that 67% of patients have IgE antibodies to the albumin/globulin fraction. CONCLUSION: Results obtained in the different tests showed common features and in agreement with other studies indicated the presence of numerous allergens in food allergy to wheat; alpha-, beta-, gamma- and omega-gliadins, LMW glutenin subunits and some water/salt-soluble proteins appeared as major IgE binding allergens, whereas HMW glutenins were only minor allergens. The same type of antigenic profile against gliadins and glutenins was observed with IgG antibodies. Important sequence or structural homologies between the various gliadins and LMW glutenin subunits could certainly explain similarity of IgE binding to these proteins.

[Circulating human pituitary prolactin cell autoantibodies and Alzheimer's disease]. / Autoanticorps circulants anti cellules a prolactine de l'hypophyse humaine et maladie d'Alzheimer.

Prolactin cell autoantibodies (PRL cells Ab) were detected in 96 p. cent of 27 cases of Alzheimer's presenile dementia and senile dementia, as defined by clinical criteria and data from CT scans. The very high frequency of these autoantibodies appears to be even more significant of Alzheimer's disease in that they were found with a similar frequency in patients with Down's syndrome aged from 13 to 33 years. The frequency of PRL cells Ab is very low in the general population including patients with endocrine disorders. Current evidence indicates that higher levels exist only in cases of arteriopathic dementia, in subjects over 80 years and in subjects with isolated organic memory disturbances, though their frequency may be such that it suggests the probability of Alzheimer's disease. The etiopathogenic significance of these autoantibodies is not clear, but they support a role of autoimmune factors in Alzheimer's disease.