Antibody responses can be up- or down-regulated by passive administration of specific antibody together with antigen. Depending on the structure of the antigen and the antibody isotype, responses can be completely suppressed or enhanced up to a 1000-fold of what is seen in animals immunized with antigen alone. IgG suppresses primary antibody responses against erythrocytes. Suppression works well in mice lacking Fc-receptors for IgG, C1q, C3, or complement receptor 1 and 2 (CR1/2). Here, we demonstrate that IgG anti-NP given to mice together with NP-conjugated sheep erythrocytes, suppresses the generation of NP-specific extra-follicular antibody-secreting cells, NP-specific germinal center B cells, induction of memory and long-lived plasma cells. IgG increases antigen clearance but this does not explain the suppressed antibody response. It is demonstrated that IgG-mediated suppression of IgG responses is epitope specific, suggesting that epitope masking is the dominant explanation for IgG-mediated suppression of antibody responses. Both IgE and IgG3 can enhance antibody responses against soluble antigens. IgE-antigen complexes bind to recirculating B cells expressing CD23, an Fc-receptor for IgE.  Thirty minutes after intravenous administration, IgE-antigen is found in splenic follicles. Subsequently, germinal center responses, antigen-specific T cell proliferation, and antibody responses are enhanced. We show that also antigen conjugated to anti-CD23 can bind to CD23+ B cells and be transported to splenic follicles. CD11+ spleen cells, rather than CD23+ B cells, present IgE-antigen complexes to T cells. Here, it is demonstrated that CD8α− conventional dendritic cells is the CD11c+ cell population presenting IgE-antigen to T cells. IgG3-mediated enhancement is dependent on CR1/2. We find that IgG3-antigen complexes, administered intravenously to mice, bind to marginal zone B cells via CR1/2. These cells then transport IgG3-antigen into splenic follicles and deposit antigen onto follicular dendritic cells. Mice treated with FTY720, a drug which dislocates marginal zone B cells from the marginal zone, impairs this transport. Studies in bone marrow chimeric mice show that CR1/2 on both B cells and follicular dendritic cells are crucial for IgG3-mediated enhancement. In summary, these observations suggest that antibodies can feedback regulate antibody responses by modulating the access of antigen to the immune system.

Les allergies alimentaires à l'arachide et au lait posent un problème majeur de santé publique, en particulier chez les enfants. Nous avons développé un modèle cellulaire de dégranulation, afin d'analyser si la liaison d'un allergène à ses IgE spécifiques, mesurée in vitro, a bien la capacité de déclencher la phase effectrice de la réaction allergique. Ce modèle repose sur l'utilisation de la lignée cellulaire RBL SX-38 développée par JP Kinet, mastocytes de rat immortalisés et modifiés pour exprimer le récepteur de haute affinité aux IgE humaines. Le développement de ce modèle pour son utilisation en microplaques de 96 puits a consisté notamment en l'optimisation de différents paramètres critiques pour la réalisation des 2 phases du test : la phase de sensibilisation des cellules par les IgE de patients allergiques et la phase de déclenchement par les allergènes auxquels le patient est sensibilisé. Ce modèle a permis de montrer l'importance des caséines et des albumines 2S (Ara h 2 et Ara h 6) dans cette étape clé de la réaction allergique au lait et à l'arachide, confirmant les observations sérologiques et cliniques disponibles. L'effet de traitements thermiques sur l'allergénicité d'un allergène majeur de l'arachide (Ara h 1), a été évalué dans le cadre du programme européen EuroPrevall. Les résultats obtenus montrent la diminution de la réactivité d'Ara h 1 après chauffage de la protéine isolée en solution. Par contre, la même protéine préparée et purifiée à partir d'arachide grillée présente une forte réactivité. Ces résultats suggèrent qu'un traitement à température élevée de la graine entraine une augmentation de l'allergénicité de Ara h 1 du fait de ses interactions avec les autres constituants de la graine. Le modèle cellulaire de dégranulation développé apparaît être un outil pertinent pour l'étude de la fonctionnalité biologique de l'interaction allergène-IgE, permettant une meilleure compréhension de la relation entre la structure d'une protéine alimentaire et son allergénicité, voire une évaluation du risque allergique des aliments ne nécessitant pas d'essais cliniques systématiques.

<p>Immunoglobulin E (IgE) is an important mediator in atopic allergies. This thesis describes the development of a therapeutic vaccine against IgE and its effects in rats and dogs. The development of an assay to determine IgE levels in dogs, and the finding of a chromosome region in rats that affects IgE levels are also reported. </p><p>The vaccine is a chimeric molecule consisting of the constant domains Cε2, Cε3 and Cε4 from IgE. The target domain of the vaccine is the Cε3 domain in the recipient species, which is the domain directly involved in receptor binding, while the flanking regions, Cε2 and Cε4, are from a distantly related mammal. In rats, the vaccine induced an immune response against circulating IgE, which decreased IgE levels by 90% and substantially reduced their allergic symptoms. Further, the effects of adjuvants in rats and dogs were evaluated, and when co-administered with the vaccine certain adjuvants were shown to increase the immune response against IgE. Mineral-oils were the most potent adjuvants in inducing a response against IgE, but metabolizable oils spiked with immunostimulatory substances were also efficient. </p><p>It was also shown that the therapeutic vaccine could induce a decrease in IgE levels in adult dogs, even though their initial levels were exceptionally high compared with humans. The IgE levels in 76 dogs ranged between 1 and 41 μg/ml while humans normally have around 150 ng/ml. However, the high IgE levels did not correlate to any specific breed, nor did they distinguish between dogs that were diagnosed as healthy and those suffering from atopic eczema, autoimmunity or skin parasites. </p><p>Regulation of total IgE levels probably involves many genes. In the final phase of the study, one candidate locus known to be involved in arthritis susceptibility in rats was investigated, and was found also to affect IgE levels.</p>

<p>Antibodies, passively administered or actively produced, regulate immune responses to the antigen they recognize. This phenomenon is called antibody-mediated feedback regulation. Feedback regulation can be positive or negative, resulting in >1000-fold enhancement or >99% suppression of the specific antibody response. The outcome depends on size, structure, dose, and route of administration of the antigen as well as on class and subclass of the regulating antibody. This thesis investigates the role of T cells in antibody-mediated feedback enhancement, using both<i> in vivo</i> and <i>in vitro</i> approaches. IgE-antibodies enhance antibody responses to small soluble proteins. This effect is entirely dependent on the low-affinity receptor for IgE, CD23, and most likely depends on increased antigen presentation by CD23⁺ B cells. Strengthening this hypothesis, we show that IgE-mediated CD4⁺ T cell proliferation<i> in vitro</i> required the presence of CD19⁺ CD43^- CD23⁺ B cells. CD23 has also been shown to negatively regulate immune responses. Transgenic mice overexpressing CD23 are known to have impaired responses to antigens in alum. We here demonstrate that they are normal regarding IgE-mediated enhancement. IgG3 enhances antibody responses, and previous data suggested involvement of complement. We found that IgG3-mediated enhancement works well in mice lacking the only Fc-receptor known to bind IgG3, CD64. Although IgG3 could enhance antibody responses it had no major effect on T cell responses. Complement-receptors 1/2 (CR1/2) are required for the initiation of normal antibody responses. Although mice lacking CR1/2 had impaired antibody responses after immunization with sheep erythrocytes, their specific T cell responses were unaffected. The presented data do not support the idea that increased complement-mediated antigen presentation is a major mechanism behind the involvement of complement in antibody responses. They support the hypothesis that antigens forming complement-containing immune complexes may activate specific B cells by co-crosslinking BCR and CR1/2.</p>

Bakgrund: Eksem förekommer hos 10-20% av barn i hela världen. En tredjedel av barnen med eksem har födoämnesallergi. Hos de flesta växer födoämnesallergin bort innan skolåldern. Förbättrat kliniskt omhändertagande och bättre förståelse av hur klinisk tolerans uppkommer är viktiga mål för forskning inom barnmedicin. Studieupplägg: Denna doktorsavhandling baseras på studier av två grupper av barn. Den första är en stor grupp med misstänkt allergi som undersökts med pricktest vid ett tillfälle. Den andra gruppen består av små barn med eksem och misstänkt födoämnesallergi. Barnen påbörjade studien innan två års ålder och har sedan följts över tid till fyra och ett halvt års ålder. Säkerhet vid pricktest: 5908 barn med en medelålder på 6 år och 5 månader, undersöktes med pricktest (SPT). Sju barn (0,12 %) reagerade med generaliserad allergisk reaktion (GAR), och behövde antiallergisk medicinering. Sju barn reagerade vasovagalt (VVR) med svimning eller ”nära-svimning”. Riskfaktorer för GAR var ålder &lt;1 år (RR 6,28) och aktivt eksem (RR 16,98). Risken för VVR var högst hos tonårsflickor och barn/ungdomar undersökta med många allergen (många prickar) samtidigt, oavsett om de var positiva eller inte. Effekt av lokalbehandling och födoämneselimination hos spädbarn med eksem: 123 barn, 52 flickor och 71 pojkar deltog i studien. Åldern varierade mellan 1-24 månader, med en medelålder på 8,4 månader vid studiens början. Kraven för att få delta var eksem och/eller misstänkt födoämnesallergi. Diagnos av eksem gjordes med stöd av Hanifin och Rajkas kriterier. Eksemgrad bedömdes med instrumentet SCORAD. Barnen bedömdes vid två tillfällen med ca sex veckors mellanrum. 62 % av barnen hade positiv pricktest för födoämnen. SCORAD-värdena i gruppen med positiv pricktest var högre än i gruppen med negativ pricktest, barnen som var födoämnessensibiliserade hade alltså svårare eksem. Efter sex veckors behandling; födoämneselimination+ lokalbehandling hos SPTpositiva barn; endast lokalbehandling hos SPT-negativa barn; var det ingen skillnad i eksemens svårighetsgrad mellan de två grupperna. Både födoämnessensibiliserade och icke födoämnessensibiliserade förbättrades signifikant av behandling. En grupp med negativ pricktest, men med påvisade antikroppar mot födoämnen i blodet (analyserade först i efterhand), som behandlades enbart med lokalbehandling förbättrade sina eksem lika mycket som de barn som också ställts på eliminationskost. Antikroppar i blod och saliv i relation till toleransutveckling: Serumnivåer av total- samt ägg- och mjölkspecifika antikroppar av IgE, IgG1 och IgG4 analyserades. I saliv analyserades totalnivåer av sekretoriskt IgA samt specifikt IgA mot mjölk och ägg. Prover togs vid studiens början, efter sex veckor samt vid 4,5 års ålder. Barn som var sensibiliserade mot mjölk och/eller ägg, men som tålde dessa födoämnen vid 4,5 års ålder hade högre IgG4 nivåer och högre IgG4/IgE-kvot vid studiens början, än de barn som ej uppnått tolerans. De högsta IgG4/IgE-kvoterna sågs hos barnen med negativt pricktest men positivt specifikt IgE i blod. Under den första korta observationsperioden på sex veckor sågs ingen påverkan på barnens antikroppsnivåer. Recept/metodutvecklande och resultat av öppna och dubbel-blinda placebokontrollerade födoämnesprovokationer: Efter recept och metodutveckling för födoämnesprovokationer med mjölk och ägg, utfördes 52 provokationer på 39 barn. Fyra barn, alla provocerade blint, reagerade på provokationen. Generella slutsatser: Risken för generaliserade allergiska reaktioner vid pricktest är liten hos barn och tonåringar, men den finns. Riskfaktorer är låg ålder och aktivt eksem. Vasovagala reaktioner är lika vanliga som generaliserade allergiska reaktioner. Lokalbehandling/smörjning ger signifikant förbättring av eksem. Elimination av födoämnen kanske inte är nödvändigt hos eksembarn med sensibilisering för mjölk och ägg under förutsättning att hudvården sköts noga. Höga IgG4/IgE-kvoter av specifika antikroppar mot födoämnen kan vara associerat med snabbare toleransutveckling, och kan stödja idén med fortsatt allergenexponering hos födoämnessensibiliserade barn. Recept på beredningar som väl maskerar komjölk och ägg, vid öppna och blindade födoämnesprovokationer, är en god hjälp vid provokationer av små barn som ofta är misstänksamma mot nya smaker och konsistenser av mat. / Background: Eczema affects at least 20 % of children worldwide, and 1/3 of them also have food allergy. In most children, the food allergy is temporary. Improved clinical management and better understanding of etiological mechanisms underlying the tolerance development are target issues in paediatric research. Study design: The thesis is based on two study groups. The first is a large group of children with suspected allergy investigated with skin prick test in a cross-sectional study. The second group is a cohort of infants with eczema and/or suspected food allergy before 2 years of age, investigated prospectively with follow-up to 4.5 years of age. Safety of skin prick test (SPT): 5908 children with a mean age of 6.4 years (range: 1 month – 18 years) were investigated with SPT. Seven children, i.e. 0.12%, displayed a generalized allergic reaction (GAR), necessitating pharmacological treatment. Seven children showed a vasovagal reaction (VVR). Risk factors for GAR were age &lt; 1 year (RR 6.28) and eczema (RR 16.98). The risk for VVR was highest among female adolescents, and children investigated with multiple skin pricks. The effect of skin care and food elimination on eczema in infants: 123 children, 52 girls and 71 boys, with a mean age of 8.4 months (range: 1-24 months) were recruited due to eczema and/or suspected food allergy. For diagnosis of eczema, the Hanifin and Rajka criteria were used, and for scoring of eczema severity SCORAD. The infants were investigated twice with an interval of 6 weeks. 62% showed positive SPTs. The SCORAD was higher among the sensitized children before treatment compared to not sensitized children. After treatment, i.e. skin care for all and elimination diet for sensitized children, there was no difference regarding eczema severity. Both SPT-positive and SPT-negative children decreased their SCORAD values significantly after treatment. A SPT-negative subgroup, with circulating specific IgE to milk/egg, was only treated with skin care, but these children improved their eczema to the same extent as those also treated with an elimination diet. Serum and salivary antibodies and achievement of tolerance Analyses were performed regarding: serum levels of total and egg- and milk-specific IgE antibodies, IgG1 and IgG4 antibodies to β-lactoglobulin (BLG) and ovalbumin (OVA); and salivary levels of total IgA, total SIgA and salivary IgA antibodies to OVA and BLG. Samples were drawn at inclusion, after 6 weeks of intervention (skin care, elimination diet), and at 4.5 years of age. Children sensitized to egg and/or milk who had developed tolerance at 4 ½ years of age had higher levels of IgG4 antibodies to OVA and BLG and also higher IgG4/IgE ratios on inclusion in the study, than those who remained non-tolerant. The highest IgG4/IgE ratios were found in children with circulating IgE antibodies to egg and/or milk but negative SPT on inclusion. The six-week treatment period did not significantly affect the levels of serum and salivary antibodies. Recipes and outcomes of open and double-blinded food challenges in children: After development of recipes for open and blinded challenge with cow’s milk and egg, 52 challenges were performed in 39 children. 4 children, challenged blindly, had a positive outcome of the challenge. General conclusions: The risk for generalized allergic reactions at SPT is low among children and teenagers, but allergic reactions do occur, and low age and eczema are risk factors. Vasovagal reactions occur as often as allergic reactions. Skin care gives significant improvement of eczema severity. Elimination diet may not be needed in infants with sensitization to milk and/or egg, provided that the skin care is adequate. High ratios of serum IgG4/IgE antibodies to food allergens may be associated with faster achievement of clinical tolerance, and may support the concept of benefit from continuing allergen exposure in sensitized children. Recipes for masking of cow’s milk and egg in open or blinded food challenges may help to accomplish challenges in young children, often suspicious to unfamiliar tastes or textures.

Immunoglobulin E (IgE) is an important mediator in atopic allergies. This thesis describes the development of a therapeutic vaccine against IgE and its effects in rats and dogs. The development of an assay to determine IgE levels in dogs, and the finding of a chromosome region in rats that affects IgE levels are also reported. The vaccine is a chimeric molecule consisting of the constant domains Cε2, Cε3 and Cε4 from IgE. The target domain of the vaccine is the Cε3 domain in the recipient species, which is the domain directly involved in receptor binding, while the flanking regions, Cε2 and Cε4, are from a distantly related mammal. In rats, the vaccine induced an immune response against circulating IgE, which decreased IgE levels by 90% and substantially reduced their allergic symptoms. Further, the effects of adjuvants in rats and dogs were evaluated, and when co-administered with the vaccine certain adjuvants were shown to increase the immune response against IgE. Mineral-oils were the most potent adjuvants in inducing a response against IgE, but metabolizable oils spiked with immunostimulatory substances were also efficient. It was also shown that the therapeutic vaccine could induce a decrease in IgE levels in adult dogs, even though their initial levels were exceptionally high compared with humans. The IgE levels in 76 dogs ranged between 1 and 41 μg/ml while humans normally have around 150 ng/ml. However, the high IgE levels did not correlate to any specific breed, nor did they distinguish between dogs that were diagnosed as healthy and those suffering from atopic eczema, autoimmunity or skin parasites. Regulation of total IgE levels probably involves many genes. In the final phase of the study, one candidate locus known to be involved in arthritis susceptibility in rats was investigated, and was found also to affect IgE levels.

Antibodies, passively administered or actively produced, regulate immune responses to the antigen they recognize. This phenomenon is called antibody-mediated feedback regulation. Feedback regulation can be positive or negative, resulting in &gt;1000-fold enhancement or &gt;99% suppression of the specific antibody response. The outcome depends on size, structure, dose, and route of administration of the antigen as well as on class and subclass of the regulating antibody. This thesis investigates the role of T cells in antibody-mediated feedback enhancement, using both in vivo and in vitro approaches. IgE-antibodies enhance antibody responses to small soluble proteins. This effect is entirely dependent on the low-affinity receptor for IgE, CD23, and most likely depends on increased antigen presentation by CD23+ B cells. Strengthening this hypothesis, we show that IgE-mediated CD4+ T cell proliferation in vitro required the presence of CD19+ CD43- CD23+ B cells. CD23 has also been shown to negatively regulate immune responses. Transgenic mice overexpressing CD23 are known to have impaired responses to antigens in alum. We here demonstrate that they are normal regarding IgE-mediated enhancement. IgG3 enhances antibody responses, and previous data suggested involvement of complement. We found that IgG3-mediated enhancement works well in mice lacking the only Fc-receptor known to bind IgG3, CD64. Although IgG3 could enhance antibody responses it had no major effect on T cell responses. Complement-receptors 1/2 (CR1/2) are required for the initiation of normal antibody responses. Although mice lacking CR1/2 had impaired antibody responses after immunization with sheep erythrocytes, their specific T cell responses were unaffected. The presented data do not support the idea that increased complement-mediated antigen presentation is a major mechanism behind the involvement of complement in antibody responses. They support the hypothesis that antigens forming complement-containing immune complexes may activate specific B cells by co-crosslinking BCR and CR1/2.

La dermatite atopique est une dermatose inflammatoire apparaissant préférentiellement avant l'âge de cinq ans, et évoluant naturellement vers la guérison après l'adolescence dans plus de 90% des cas. L'origine de cette amélioration spontanée n'est pas clairement établie dans cette dermatose multifactorielle dont l'étiopathogénie reste encore à déterminer (maturation du système immunitaire ?). Les liens de cette pathologie avec le psychisme sont certains : retentissement psychologique important avec altération de la qualité de vie, aggravation voire déclenchement des poussées par le stress, amélioration des lésions par psychothérapie. L'observation de la nature de la structure d'attachement est importante dans le domaine de la psychopathologie. Elle est encore peu réalisée dans le domaine da la pathologie organique. Nous avons étudié la structure d'attachement de 80 adultes ayant présenté dans l'enfance une dermatite atopique, 40 d'entre eux ayant une guérison de celle-ci depuis l'adolescence, 40 autres présentant une pérennisation des crises d'eczéma. L'évaluation de l'attachement a été réalisée avec un autoquestionnaire (CAMIR de PIERREHUMBERT) et la cotation de l'entretien d'attachement avec la méthode Q-SORT selon KOBAK. Nous avons également mesuré les symptômes psychopathologiques associés avec l'échelle SCL90-R, le niveau d'anxiété avec l'inventaire trait-état de SPIELBERGER (STAIY) et le coping avec le WCC-R de VITALIANO. Les IgE totales ont été dosées. Les sujets avec dermatite atopique ayant débutée avant trois ans ne sont pas plus insécures que ceux avec un début plus tardif de leur dermatose. Ceci fait évoquer la possibilité d'une absence de retentissement sur la structure d'attachement d'une dermatite atopique apparaissant dans les premiéres années de vie, contrairement à ce qui est noté dans toute pathologie chronique d'apparition précoce. Il est alors supposé un effet positif des soins cutanés sur la nature de la relation de la dyade mère-enfant. Par contre, le retentissement ultérieur de la dermatite atopique chez l'adulte est important, avec augmentation d'une insécurité préoccupée en termes de représentations d'attachement, une augmentation des scores de toutes les dimensions psychopathologiques mesurées et une recherche anxieuse de soutien à l'extérieur. Ce retentissement est d'autant plus important que les IgE sont élevées, ceci n'étant pas uniquement le reflet de la gravité de la maladie. Les adultes présentant une dermatite atopique pérennisée sont structurellement plus insécures que ceux qui ont guéris : si nous considèrons l'aspect stable dans le temps de la structure d'attachement, ces résultats positionneraient celle ci en tant que possible facteur dispositionnel prédictif dans l'évolution de la dermatite atopique. Le score de sécurité des patients guéris est d'autant plus élevé que les IgE sont normales. Un phénomène d'interaction entre le système d'attachement et le système adaptatif au stress, à dépendance développementale commune sur certains aspects, est évoqué. Le rôle des IgE reste à déterminer. En termes de psychologie de la santé, la structure d'attachement pourrait être considérée comme un facteur dispositionnel susceptible d'influer l'évolution de la dermatite atopique.

Antibodies can enhance or suppress the immune responses against their specific antigens. This phenomenon is known as antibody-mediated feedback regulation. We have studied the mechanisms underlying IgE-, IgM-, and IgG3-mediated enhancement of immune responses in mouse models using intravenous immunization. We attempted to answer the following questions: 1) Which cell type presents IgE-complexed antigens to CD4+ T cells? 2) Is complement activation required for specific IgM to enhance antibody responses? 3) Does IgM enhance CD4+ T-cell responses? 4) How are IgG3-antigen complexes transported into B-cell follicles? We found that CD23+ B cells transporting IgE-antigen complexes into B-cell follicles were not required to prime the antigen-specific CD4+ T cells in vivo, whereas CD11c+ cells were indispensable. After examining the three most common subpopulations of CD11c+ cells in the spleen, we determined that it was CD8α- conventional dendritic cells migrating into the T-cell zone following immunization that presented IgE-complexed antigens to CD4+ T cells. Next, we showed that specific IgM from Cµ13 mice, which is unable to activate complement, failed to enhance either antibody or germinal center responses whereas wild-type IgM enhanced both responses. Therefore, specific IgM must activate complement to enhance humoral responses. In addition, wild-type IgM did not up-regulate CD4+ T-cell responses. Finally, we showed that IgG3-antigen complexes were transported by marginal zone B cells into B-cell follicles via binding to complement receptors 1 and 2 (CR1/2) on those cells. The immune complexes were captured by follicular dendritic cells as early as 2 h after immunization. Germinal center responses were also enhanced by IgG3. Using bone marrow chimeric mice, we found that CR1/2 expression was required on both marginal zone B cells and follicular dendritic cells to provide an optimal enhancement of antibody responses.

La dermatite atopique est une dermatose inflammatoire apparaissant préférentiellement avant l’âge de cinq ans, et évoluant naturellement vers la guérison après l’adolescence dans plus de 90% des cas. L’origine de cette amélioration spontanée n’est pas clairement établie dans cette dermatose multifactorielle dont l’étiopathogénie reste encore à déterminer (maturation du système immunitaire ?). Les liens de cette pathologie avec le psychisme sont certains : retentissement psychologique important avec altération de la qualité de vie, aggravation voire déclenchement des poussées par le stress, amélioration des lésions par psychothérapie. L’observation de la nature de la structure d’attachement est importante dans le domaine de la psychopathologie. Elle est encore peu réalisée dans le domaine da la pathologie organique. Nous avons étudié la structure d’attachement de 80 adultes ayant présenté dans l’enfance une dermatite atopique, 40 d’entre eux ayant une guérison de celle-ci depuis l’adolescence, 40 autres présentant une pérennisation des crises d’eczéma. L’évaluation de l’attachement a été réalisée avec un autoquestionnaire (CAMIR de PIERREHUMBERT) et la cotation de l’entretien d’attachement avec la méthode Q-SORT selon KOBAK. Nous avons également mesuré les symptômes psychopathologiques associés avec l’échelle SCL90-R, le niveau d’anxiété avec l’inventaire trait-état de SPIELBERGER (STAIY) et le coping avec le WCC-R de VITALIANO. Les IgE totales ont été dosées. Les sujets avec dermatite atopique ayant débutée avant trois ans ne sont pas plus insécures que ceux avec un début plus tardif de leur dermatose. Ceci fait évoquer la possibilité d’une absence de retentissement sur la structure d’attachement d’une dermatite atopique apparaissant dans les premiéres années de vie, contrairement à ce qui est noté dans toute pathologie chronique d’apparition précoce. Il est alors supposé un effet positif des soins cutanés sur la nature de la relation de la dyade mère-enfant. Par contre, le retentissement ultérieur de la dermatite atopique chez l’adulte est important, avec augmentation d’une insécurité préoccupée en termes de représentations d’attachement, une augmentation des scores de toutes les dimensions psychopathologiques mesurées et une recherche anxieuse de soutien à l’extérieur. Ce retentissement est d’autant plus important que les IgE sont élevées, ceci n’étant pas uniquement le reflet de la gravité de la maladie. Les adultes présentant une dermatite atopique pérennisée sont structurellement plus insécures que ceux qui ont guéris : si nous considèrons l’aspect stable dans le temps de la structure d’attachement, ces résultats positionneraient celle ci en tant que possible facteur dispositionnel prédictif dans l’évolution de la dermatite atopique. Le score de sécurité des patients guéris est d’autant plus élevé que les IgE sont normales. Un phénomène d’interaction entre le système d’attachement et le système adaptatif au stress, à dépendance développementale commune sur certains aspects, est évoqué. Le rôle des IgE reste à déterminer. En termes de psychologie de la santé, la structure d’attachement pourrait être considérée comme un facteur dispositionnel susceptible d’influer l’évolution de la dermatite atopique. / Atopic dermatitis is an inflammatory skin disorder which usually appears before the age of five, and heals naturally little by little after adolescence in over 90% of cases. Why this spontaneous improvement occurs is not clearly established for this multi-factor skin disorder, for which the etiopathology has yet to be determined (immune system maturity?).There is a clear relationship between this pathology and the psyche: major psychological repercussions affecting the quality of life, aggravation or triggering of skin reactions due to stress, alleviation of lesions using psychotherapy. Observation of patterns of attachment is important in the field of psychopathology, but is not often undertaken in the domain of organic pathology. We studied the patterns of attachment for 80 adults having suffered from atopic dermatitis during childhood, 40 of them had been cured since adolescence, the other 40 continued to suffer from outbreaks of eczema. Attachment was evaluated using a self-completion questionnaire (CAMIR by PIERRE HUMBERT) and the attachment interview was graded using the Q-SORT method, by KOBAK. We also measured the associated psychopathological symptoms using the SCL90-R scale, level of anxiety using SPIELBERGER’s state-trait-anxiety inventory (STAIY), and coping measurement using the WCC-R scale devised by VITALIANO. Total IgE was measured. Patients suffering from atopic dermatitis that began before the age of 3 years are not more insecure than patients whose skin disorder started later in life. This meant that there were possibly no repercussions on the pattern of attachment for cases of atopic dermatitis that had appeared in the first years of life, contrary to all reports regarding a chronic pathology appearing early in life. This implies that caring for the skin has a positive effect on the mother-child relationship. On the other hand, adults suffer from major repercussions of atopic dermatitis later on in life: increased sense of preoccupied insecurity in terms of representations of attachment, increased scores in all the psychopathological dimensions measured, and an anxious need for outside support. These repercussions are even more serious when IgE is high, but this is not solely connected with the gravity of the illness. Adults suffering from persistent atopic dermatitis are basically more insecure than those who are cured: if long-term stability in the pattern of attachment is considered, this study could place pattern of attachment as a possible predictive disposition factor in the evolution of atopic dermatitis. The security score of cured patients is all the greater when IgE is normal. The existence of an interaction between the attachment pattern and the system for adapting to stress has been suggested, since they are both dependent on development. The role played by IgE remains to be determined. In terms of health psychology, the pattern of attachment could be considered as a disposition factor likely to influence the evolution of a skin disorder.