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CRUE-CSIC (Acuerdos Transformativos 2022), Innate immune cells experience long lasting metabolic and epigenetic changes after an encounter with specific stimuli. This facilitates enhanced immune responses upon secondary exposition to both the same and unrelated pathogens, a process termed trained immunity. Trained immunity- based vaccines (TIbV) are vaccines able to induce innate immune memory, thus conferring heterologous protection against a broad range of pathogens. While trained immunity has been well documented in the con-text of infections and multiple immune- mediated diseases, the role of innate immune memory and its contribution to the initiation and maintenance of chronic allergic dis-eases remains poorly understood. Over the last years, different studies attempting to uncover the role of trained immunity in allergy have emerged. Exposition to en-vironmental factors impacting allergy development such as allergens or viruses in-duces the reprogramming of innate immune cells to acquire a more pro-inflammatory phenotype in the context of asthma or food allergy. Several studies have convincingly demonstrated that prevention of viral infections using TIbV contributes to reduce wheezing attacks in children, which represent a high- risk factor for asthma develop-ment later in life. Innate immune cells trained with specific stimuli might also acquire anti- inflammatory features and promote tolerance, which may have important impli-cations for chronic inflammatory diseases such as allergies. Recent findings showed that allergoid- mannan conjugates, which are next generation vaccines for allergen- specific immunotherapy (AIT), are able to reprogram monocytes into tolerogenic den-dritic cells by mechanisms depending on metabolic and epigenetic rewiring. A better understanding of the underlying mechanisms of trained immunity in allergy will pave the way for the design of novel trained immunity- based allergen vaccines as potential alternative strategies for the prevention and treatment of allergic diseases., Ministerio de Ciencia Innovación, Fac. de Ciencias Químicas, TRUE, pub

Ovarian cancer is a disease with a high rate of mortality where the need for novel treatments will increase in the near future as older and populous generations reach the age where the cancer is usually diagnosed. Once treated, ovarian cancer tends to recur and display a newfound resistance against the platinum-based chemotherapeutic drugs that are used to treat the disease. Therefore, devising new methods of treatment is of utmost importance. Treatment with oncolytic viruses like LOAd703 offers an alternative treatment option that is more specific, causes immunogenic cell death in tumor cells, can stimulate the patient’s own immune system into fighting the cancer, and also has the potential to induce long term immune memory. In this project, the oncolytic and immunogenic capacity of LOAd703 in three different ovarian cancer cell lines was tested in conjunction with the standard-of-care chemotherapeutical drugs paclitaxel, cisplatin and carboplatin. The chemotherapy did not inhibit the replication, transgene expression or oncolysis of the LOAd703 virus. LOAd703 was able to effectively induce oncolysis in all three cell lines. The oncolytic capacity was generally increased when combined with chemotherapeutics. In cells resistant to chemotherapeutics, combination therapy with LOAd703 increased the killing capacity. While combination therapy proved effective, it did leave behind a small population of tumor cells that appeared to be resistant to both chemotherapy and viral oncolysis but longer culturing times may be tested to evaluate if complete killing will occur or if it is a primary resistance to these treatments in the cell lines. Further, if there is resistance to oncolysis or chemotherapy-mediated killing, employing tumor-immune cell co-cultures or in vivo studies might be necessary in order to assess whether the immunostimulatory effects of LOAd703 will lead to a complete eradication of the remaining tumor cells. The treatments also caused an increase in the exp

Ovarian cancer is a disease with a high rate of mortality where the need for novel treatments will increase in the near future as older and populous generations reach the age where the cancer is usually diagnosed. Once treated, ovarian cancer tends to recur and display a newfound resistance against the platinum-based chemotherapeutic drugs that are used to treat the disease. Therefore, devising new methods of treatment is of utmost importance. Treatment with oncolytic viruses like LOAd703 offers an alternative treatment option that is more specific, causes immunogenic cell death in tumor cells, can stimulate the patient’s own immune system into fighting the cancer, and also has the potential to induce long term immune memory. In this project, the oncolytic and immunogenic capacity of LOAd703 in three different ovarian cancer cell lines was tested in conjunction with the standard-of-care chemotherapeutical drugs paclitaxel, cisplatin and carboplatin. The chemotherapy did not inhibit the replication, transgene expression or oncolysis of the LOAd703 virus. LOAd703 was able to effectively induce oncolysis in all three cell lines. The oncolytic capacity was generally increased when combined with chemotherapeutics. In cells resistant to chemotherapeutics, combination therapy with LOAd703 increased the killing capacity. While combination therapy proved effective, it did leave behind a small population of tumor cells that appeared to be resistant to both chemotherapy and viral oncolysis but longer culturing times may be tested to evaluate if complete killing will occur or if it is a primary resistance to these treatments in the cell lines. Further, if there is resistance to oncolysis or chemotherapy-mediated killing, employing tumor-immune cell co-cultures or in vivo studies might be necessary in order to assess whether the immunostimulatory effects of LOAd703 will lead to a complete eradication of the remaining tumor cells. The treatments also caused an increase in the exp

BackgroundInborn errors of immunity (IEI) are a group of genetic disorders that impair the immune system, with over 400 genes described so far, and hundreds more to be discovered. To facilitate the search for new genes, we need a way to prioritize among all the genes in the genome those most likely to play an important role in immunity.ResultsHere we identify a new list of genes by linking known IEI genes to new ones by using open-source databases of protein-protein interactions, post-translational modifications, and transcriptional regulation. We analyze this new set of 2,530 IEI-related genes for their tolerance of genetic variation and by their expression levels in various immune cell types.ConclusionsBy merging genes derived from protein interactions of known IEI genes with transcriptional data, we offer a new list of candidate genes that may play a role in as-yet undiscovered IEIs.

BackgroundInborn errors of immunity (IEI) are a group of genetic disorders that impair the immune system, with over 400 genes described so far, and hundreds more to be discovered. To facilitate the search for new genes, we need a way to prioritize among all the genes in the genome those most likely to play an important role in immunity.ResultsHere we identify a new list of genes by linking known IEI genes to new ones by using open-source databases of protein-protein interactions, post-translational modifications, and transcriptional regulation. We analyze this new set of 2,530 IEI-related genes for their tolerance of genetic variation and by their expression levels in various immune cell types.ConclusionsBy merging genes derived from protein interactions of known IEI genes with transcriptional data, we offer a new list of candidate genes that may play a role in as-yet undiscovered IEIs.

With the advancement of high-throughput DNA/RNA sequencing and computational analysis techniques, commensal bacteria are now considered almost as important as pathological ones. Understanding the interaction between these bacterial microbiota, host and asthma is crucial to reveal their role in asthma pathophysiology. Several airway and/or gut microbiome studies have shown associations between certain bacterial taxa and asthma. However, challenges remain before gained knowledge from these studies can be implemented into clinical practice, such as inconsistency between studies in choosing sampling compartments and/or sequencing approaches, variability of results in asthma studies, and not taking into account medication intake and diet composition especially when investigating gut microbiome. Overcoming those challenges, will help to better understand the complex asthma disease process. The therapeutic potential of using pro- and pre-biotics to prevent or reduce risk of asthma exacerbations requires further investigation. This review will focus on methodological issues regarding setting up a microbiome study, recent developments in asthma bacterial microbiome studies, challenges and future therapeutic potential. This article is protected by copyright. All rights reserved.

Introduction: rheumatic diseases are a group of conditions that are characterized by the presence, usually, of pain, inflammation, deformity, functional disability and decreased perception of quality of life related to health. Cardiovascular complications are frequent in the course of these diseases; Nutritional disorders may be the cause or consequence of these complications. Objective: to determine the relationship between body adiposity and blood pressure in children and adolescents with rheumatic diseases.Methodology: descriptive, cross-sectional study in 45 patients with rheumatic diseases diagnosed according to the criteria of the American College of Reumathology. The bioimpedance technique was used to determine the percentage of body fat and Pearson's correlation index to determine the relationship between variables.Results: average age of 12.26 ± 8.74 years, predominance of female patients (68.69%) and between 15 and 18 years of age (42.22%). The most represented rheumatic disease was juvenile idiopathic arthritis (46.67%). Patients with increased fat percentage predominated, where overweight (44.44%) and obesity (20.0%) were the most represented. 20.0% of the patients included in the investigation presented alterations in blood pressure, predominantly in obese patients (33.33%) and overweight (20.0%). Conclusions: Maintaining adequate control of body adiposity considerably reduces the possibility of the appearance of blood pressure disorders. The electric bioimpedance is a method of easy application and proven effectiveness to determine the percentage of fat., Introducción: las enfermedades reumáticas son un grupo de afecciones que se caracterizan por la presencia, generalmente, de dolor, inflamación, deformidad, discapacidad funcional y disminución de la percepción de calidad de vida relacionada con la salud. Las complicaciones cardiovasculares son frecuentes en el curso de estas enfermedades; los trastornos nutricionales pueden ser causa o consecuencia de estas complicaciones. Objetivo: determinar la relación existente entre adiposidad corporal y presión arterial en niños y adolescentes con enfermedades reumáticas. Métodos: estudio descriptivo, de corte transversal en 45 pacientes con enfermedades reumáticas diagnosticadas según los criterios del American College of Reumathology. Se utilizó la técnica de bioimpedancia para determinar el porcentaje de grasa corporal e índice de correlación de Pearson para determinar relación entre variable. Resultados: promedio de edad de 12,26 ± 8,74 años, predominio de pacientes femeninas (68,69 %) y entre 15 y 18 años de edad (42,22 %). La enfermedad reumática más representada fue la artritis idiopática juvenil (46,67 %). Predominaron los pacientes con aumento del porcentaje de grasa, donde el sobrepeso (44,44 %) y la obesidad (20,0 %) fueron los más representados. El 20,0 % de los pacientes incluidos en la investigación presentaron alteraciones de la presión arterial con predominio en pacientes obesos (33,33 %) y con sobrepeso (20,0 %). Conclusiones: Mantener un adecuado control de la adiposidad corporal disminuye considerablemente la posibilidad de aparición de trastornos de la presión arterial. La bioimpedancia eléctrica es un método de fácil aplicación y de comprobada efectividad para determinar el porcentaje de grasa.

Introduction: in the undergraduate training must be given due importance to the teaching of rheumatology because of its multidisciplinary character, which demands a future health professional able to assess and recognize even from classrooms and laboratories, the social and health implications between rheumatic and ocular diseases because the correct diagnosis of these can help highlighting the role of the systemic process and vice versa.Objective: to assess the level of medical students´ knowledge about the most common ophthalmological conditions in the practice of rheumatology.Methods: the research was carried out in the Faculty of Medicine belonging to the Universidad Regional Autonomy de los Andes from March to May, 2017. It is a descriptive, transversal and analytical study. The universe was constituted by 166 students of sixth and seventh semesters and the sample of study was constituted by 75 students of each semester selected at random. The majority presence of women characterizes the sample object of study (53.3 % against 46.7 % of men). The maximum and minimum ages were 21 and 26 years old respectively, with a higher average age in the seventh semester. A previously validated survey was applied that allowed evaluating the knowledge related to the most frequent ophthalmologic manifestations.Conclusions: the level of knowledge on the ophthalmologic manifestations in the practice of rheumatology is not good, so it is suggested to resize the teaching process, favoring the practical training that must characterize the teaching of undergraduate to deepen the management of these entities., Introducción: en la formación de pregrado debe concederse la debida importancia a la enseñanza de la reumatología dado su carácter multidisciplinar, que demanda un futuro profesional de la salud capaz de valorar y reconocer aún desde aulas y laboratorios, las implicaciones sociales y de salud entre enfermedades reumáticas y oculares ya que el diagnóstico correcto de estas, puede ayudar a destacar el rol del proceso sistémico y viceversa.Objetivo: evaluar el nivel de conocimientos de estudiantes de medicina sobre las afecciones oftalmológicas más frecuentes en la práctica de la reumatología. Métodos: la investigación se realizó en la facultad de Medicina perteneciente a la Universidad Regional Autónoma de los Andes en el período comprendido de marzo a mayo de 2017. Se trata de un estudio descriptivo, transversal y analítico. El universo estuvo constituido por 166 estudiantes de VI y VII semestres y la muestra de estudio la constituyeron 75 estudiantes de cada semestre seleccionados al azar. La presencia mayoritaria de mujeres caracteriza a la muestra objeto de estudio (53.3 %, contra 46,7 % de hombres). Las edades máxima y mínima fueron 21 y 26 años respectivamente, con edad promedio superior en el VII semestre. Se aplicó una encuesta validada previamente que permitió evaluar el conocimiento relacionado con las manifestaciones oftalmológicas más frecuentes.Conclusiones: el nivel de conocimiento sobre las manifestaciones oftalmológicas en la práctica de la reumatología no es bueno, por lo que se sugiere redimensionar el proceso docente, privilegiando la formación práctica que debe caracterizar la enseñanza de pregrado al profundizar en el manejo de estas entidades.

Introduction: rheumatic diseases and musculoskeletal diseases are manifested by alterations in the locomotor system, although behind them there may be a disorder of the immune response that leads to the attention of these patients should not focus only on the local aspects, but also in its systemic assessment for the involvement of organs and organ systems such as cardiovascular, respiratory, renal and digestive.Objective: To review current advances and trends in the use of local anesthesia in patients with rheumatic diseases.Development: The treatment of these diseases consists mainly of glucocorticoids, non-steroidal anti-inflammatory drugs and disease modifying drugs, in addition to which antirheumatic drugs are increasingly available, although some still require more evidence for its widespread use.Conclusions: Local anesthesia is one of the therapeutic alternatives that is generally used intra-articularly in rheumatic patients, as well as other medications. In the search for new substances that induce longer periods of analgesia has been intruded into the use of adjuvants or additives, which are drugs that are associated in a synergistic manner with local anesthetics and prolong the duration of sensorimotor block, attenuating the sensation painful and this allows to restrict the required cumulative dose of local anesthetics. Important advances are reported in this regard and perspectives are broadened by the results of the investigations., Introducción: las enfermedades reumáticas (ER) y muscoloesqueléticas (MEs) se manifiestan por alteraciones en el aparato locomotor, aunque detrás de ellas puede haber un trastorno de la respuesta inmunológica que conlleva a que la atención de estos pacientes no se deba centrar solo en los aspectos locales, sino también en su valoración sistémica por la afectación de órganos y sistemas de órganos como el cardiovascular, respiratorio, renal y digestivo.Objetivo: revisar los avances y tendencias actuales del uso de la anestesia local en pacientes con enfermedades reumáticas. Desarrollo: el tratamiento de estas enfermedades está constituido fundamentalmente por glucocorticoides (GC), los antinflamatorios no esteroideos (AINE) y los fármacos modificadores de enfermedad (FAME), además de que cada vez más están disponibles medicamentos antirreumáticos, aunque algunos aún requieren de mayor evidencia para su utilización generalizada.Conclusiones: la anestesia local es una de las alternativas terapéuticas que generalmente, por vía intra articular, se emplea en los pacientes reumáticos, al igual que otros medicamentos. En la búsqueda de nuevas sustancias que induzcan mayores períodos de analgesia se ha incursionado en el empleo de adyuvantes o aditivos, que son medicamentos que se asocian de manera de sinérgica con los anestésicos locales y prolongan la duración del bloqueo sensorio-motor, atenuando la sensación dolorosa y esto permite restringir la dosis acumulativa requerida de anestésicos locales. Se reportan importantes avances en este sentido y se amplían las perspectivas por los resultados de las investigaciones.

Introduction: Aphthae and oral ulcers are a frequent reason for consulting the stomatologist. Aphthous are a particular form of oral ulceration. Aphtosis is defined by the recurrent nature of multiple aphthae that progress through episodes of 3-10 days and are repeated at least twice a year.Objective: To describe the main aspects of the Behçet disease that could be useful to the stomatologist.Development: Behçet's disease is an immune-mediated systemic vasculitis characterized by a characteristic triad of ocular lesions, recurrent oral and genital ulcers. Oral aphtosis and Behçet's disease seem to be due to the same pathogenic mechanism, but we still have to find the reasons why the former is limited to the oral cavity and the latter is systemic. Because recurrent oral ulcers are found in the same way in this disease and EB, it should be considered as a differential diagnosis of EB.Conclusions: The role of stomatologists is important to establish the diagnosis of Behçet's disease, since they could be the first to detect it. Recurrent oral ulcers are a common initial symptom of EB. A multidisciplinary approach is required to diagnose and treat the disease., Introducción: Las aftas y ulceraciones bucales constituyen un motivo frecuente de consulta al estomatólogo. El afta es una forma particular de ulceración bucal. la aftosis se define por el carácter recidivante de aftas múltiples que evolucionan por episodios de 3-10 días y se repiten por lo menos dos veces al año.Objetivo: Abordar los principales aspectos de la Enfermedad de Behçet que podrían ser útiles al estomatólogo.Desarrollo: La enfermedad de Behçet es una vasculitis sistémica inmunomediada caracterizada por una triada característica de lesiones oculares, úlceras orales y genitales recurrentes. La aftosis bucal y la enfermedad de Behçet parecen deberse al mismo mecanismo patogénico, pero aún falta por encontrar las razones por las cuáles la primera se limita a la cavidad bucal y la segunda es sistémica. Debido a que las úlceras orales recurrentes se encuentran en de igual forma en esta enfermedad y la EB, debe considerarse como diagnóstico diferencial de EB. Conclusiones: El papel de los estomatólogos es importante para establecer el diagnóstico de Enfermedad de Behçet, ya que podrían ser los primeros en detectarla. Las úlceras orales recurrentes son un síntoma inicial común de EB. Se requiere un enfoque multidisciplinario para diagnosticar y tratar la enfermedad.

Background and Objectives: The development of childhood asthma is associated with neonatal colonization with pathogenic bacteria in hypopharynx. Furthermore, established asthma is associated with systemic low-grade inflammation. We here report on the association between neonatal colonization with pathogenic bacteria in hypopharynx and the development of systemic low-grade inflammation. Methods: Bacterial colonization of the hypopharynx with M. catharralis, H. influenzae and/or S. pneumoniae was assessed in asymptomatic children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000 ) cohort at age 1 month by culturing technique (N=238) and by quantitative polymerase chain reaction (qPCR) technique (N=249) and in the COPSAC2010 cohort by culturing at age 1 month (N=622) and again at age 3 months (N=613). Systemic low-grade inflammation was determined in both cohorts at age 6 months by measuring plasma levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukine-6 (lL-6). Results: In both cohorts, bacterial colonization was associated with increased levels of hs-CRP: COPSAC2000 , 1 month culturing (geometric mean ratio of colonized/non-colonized [95% CI]), 1.39 [0.97-2.01], p=0.08, 1 month qPCR, 1.55 [1.14-2.10], p<0.01. A multi‐parametric principal component analysis incorporating hs‐CRP, TNF‐α and IL‐6 confirmed a systemic inflammatory profile in children colonized with M. catharralis, H. influenzae and/or S. pneumoniae in the hypopharynx compared to non‐colonized children (p‐values<0.05). Conclusion: The composition of the upper airway microbiome in early life may cause systemic low‐grade inflammation.

Background: Cat allergy is a major trigger of asthma world-wide. Molecular patterns of cat sensitization vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied. Objective: To investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type-2 inflammation and total IgE among young asthmatic subjects sensitized to furry animals. Methods: Patients with asthma (age 10-35 years; n = 266) and IgE sensitization to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE-antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders. Results: The level of IgE against Fel d 2 was independently related to FeNO (P = .012) and total IgE (P < .001), and IgE against Fel d 4 associated with B-Eos count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat extract did not independently relate to these inflammatory markers (P = .23-.51). Conclusions: Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type-2 biomarkers and total IgE in young asthmatics. Clinical relevance: We suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects.

Background: Allergy to penicillin is commonly reported in the community. However, the majority of patients are not allergic when formally tested. In low risk patients, rapid allergy testing has been performed with skin prick/intradermal or direct oral challenge in an outpatient and Emergency Department setting. However, a direct oral challenge in acute hospital inpatient has not been reported. Aim(s): To access the feasibility and safety of rapid penicillin allergy delabelling with direct oral challenge in admitted acute general medical patients. Method(s): Patients admitted to a general medicine unit were screened for a history of penicillin allergy by unit pharmacists. A detailed history was obtained on patients with a self-reported penicillin allergy to assess suitability for a direct oral challenge: including current clinical status, and pretest probability based on the Australian Society of Allergy and Clinical Immunology (ASCIA) Guidelines. Suitable patients where challenged with a single 250mg Amoxicillin oral dose, followed by a 3 days course of 250mg Amoxicillin TDS. Result(s): 1808 patients were admitted to a general medicine unit from February to June 2018. 181 (10%) patients had a documented penicillin allergy. Rash (45%) is most commonly reported followed by unknown/non-specific reaction (21%) and gastro-intestinal symptoms (10%). Only 28 (16%) of patients met criteria for high pre-test probability of reaction. 35 (19%) patients were recruited to a challenge. 34 patients tolerated the challenge without any reactions. Only 1 patient reported a rash. 13 patients had been de-labelled from June 2017 to February 2018 using the same protocol, resulting in total of 47 patients successfully de-labelled since June 2017. Data collection is ongoing. Conclusion(s): Penicillin allergy de-labelling with a direct oral challenge in an acute hospital inpatient setting is likely safe and feasible. This approach may improve patient outcome with better anti-microbial usage

Background: Allergy to penicillin is commonly reported in the community. However, the majority of patients are not allergic when formally tested. In low risk patients, rapid allergy testing has been performed with skin prick/intradermal or direct oral challenge in an outpatient and Emergency Department setting. However, a direct oral challenge in acute hospital inpatient has not been reported. Aim(s): To access the feasibility and safety of rapid penicillin allergy delabelling with direct oral challenge in admitted acute general medical patients. Method(s): Patients admitted to a general medicine unit were screened for a history of penicillin allergy by unit pharmacists. A detailed history was obtained on patients with a self-reported penicillin allergy to assess suitability for a direct oral challenge: including current clinical status, and pretest probability based on the Australian Society of Allergy and Clinical Immunology (ASCIA) Guidelines. Suitable patients where challenged with a single 250mg Amoxicillin oral dose, followed by a 3 days course of 250mg Amoxicillin TDS. Result(s): 1808 patients were admitted to a general medicine unit from February to June 2018. 181 (10%) patients had a documented penicillin allergy. Rash (45%) is most commonly reported followed by unknown/non-specific reaction (21%) and gastro-intestinal symptoms (10%). Only 28 (16%) of patients met criteria for high pre-test probability of reaction. 35 (19%) patients were recruited to a challenge. 34 patients tolerated the challenge without any reactions. Only 1 patient reported a rash. 13 patients had been de-labelled from June 2017 to February 2018 using the same protocol, resulting in total of 47 patients successfully de-labelled since June 2017. Data collection is ongoing. Conclusion(s): Penicillin allergy de-labelling with a direct oral challenge in an acute hospital inpatient setting is likely safe and feasible. This approach may improve patient outcome with better anti-microbial usage

Aims/hypothesis: Enterovirus infections have been associated with the development of type 1 diabetes in multiple studies, but little is known about enterovirus-induced responses in children at risk for developing type 1 diabetes. Our aim was to use genome-wide transcriptomics data to characterise enterovirus-associated changes in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Methods: Longitudinal whole-blood samples (356 samples in total) collected from 28 pairs of children at increased risk for developing type 1 diabetes were screened for the presence of enterovirus RNA. Seven of these samples were detected as enterovirus-positive, each of them collected from a different child, and transcriptomics data from these children were analysed to understand the individual-level responses associated with enterovirus infections. Transcript clusters with peaking or dropping expression at the time of enterovirus positivity were selected as the enterovirus-associated signals. Results: Strong signs of activation of an interferon response were detected in four children at enterovirus positivity, while transcriptomic changes in the other three children indicated activation of adaptive immune responses. Additionally, a large proportion of the enterovirus-associated changes were specific to individuals. An enterovirus-induced signature was built using 339 genes peaking at enterovirus positivity in four of the children, and 77 of these genes were also upregulated in human peripheral blood mononuclear cells infected in vitro with different enteroviruses. These genes separated the four enterovirus-positive samples clearly from the remaining 352 blood samples analysed. Conclusions/interpretation: We have, for the first time, identified enterovirus-associated transcriptomic profiles in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Our results provide a starting point for understanding the individual response

Background Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972–2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11–22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972–2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11–22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972–2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11–22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972–2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11–22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Background: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. Objective: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. Methods: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972–2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. Results: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11–22 years with information on parental disease activity both before and after birth. Conclusion & Clinical Relevance: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

BACKGROUND: We have reported that increased fraction of exhaled nitric oxide (FeNO), a measure of TH2 -driven airway inflammation, and blood eosinophil count, a marker of systemic eosinophil inflammation, correlated with asthma attacks in a population-based study. OBJECTIVE: To investigate the relation between simultaneously elevated FeNO and serum eosinophil cationic protein (S-ECP) levels and asthma events among asthmatics. METHODS: Measurements of FeNO (elevated ≥ 25 ppb) and S-ECP (elevated ≥ 20 ng/mL) were done in 339 adult asthmatics. Asthma events (attacks and symptoms) were self-reported. RESULTS: Simultaneously normal S-ECP and FeNO levels were found in 48% of the subjects. Subjects with simultaneously elevated S-ECP and FeNO (13% of the population) had a higher prevalence of asthma attacks in the preceding 3 months than subjects with normal S-ECP and FeNO (51% vs. 25%, p = 0.001). This was not found for subjects with singly elevated S-ECP (p = 0.14) or FeNO (p = 0.34) levels. Elevated S-ECP and FeNO levels was independently associated to asthma attacks in the preceding 3 months after adjusting for potential confounders (OR (95% CI) 4.2 (2.0-8.8). CONCLUSIONS: Simultaneous elevated FeNO and S-ECP related to a higher likelihood of asthma attacks in the preceding 3 months. This indicates that there is a value in measuring both FeNO and systemic eosinophilic inflammation in patients with asthma in order to identify individuals at high risk of exacerbations.

Type 1 diabetes (T1D) is a tissue specific autoimmune disease that result from the targeted destruction of the insulin-secreting beta cells in the pancreatic islets. A hallmark of T1D is the infiltration of autoimmune T cells into the islets that is predominantly composed of CD8+ T cells. The strongest genetic association with susceptibility to T1D are to the human leukocyte antigen (HLA) genes, particularly the class II, and to a lesser extent, the class I HLA genes. The class I HLA genes encode for cell surface HLA molecules that constitutively present endogenous antigenic peptides for scrutiny by incoming CD8+ T cells. Autoantigens involved in T1D have been widely characterised, however, little is known about the identities of autoantigenic peptides presented by less studied alleles and the nature of naturally processed and presented CD8+ T cell epitopes that leads to a targeted beta cell destruction as disease unfolds. In this study, the nature of bound peptide antigens (immunopeptidomes) restricted to a panel of T1D associated class I HLA allotypes (HLA-A*01:01, -A*02:01, -A*24:02, - B*08:01 and –B*18:01) were studied in depth using advanced mass spectrometry techniques. First I assessed the immunopeptidomes of C1R cell lines that were individually transfected with each HLA allotype. An extensive class I ligand dataset (up to 18 600 naturally presented peptides) was identified in this study which allowed the extension and clarification of previously reported binding motifs for these class I HLA molecules. We found no differences in the nature of peptide presentation by T1D disease predisposing and protective HLAs. Overall, features (subcellular localisation and biological functions) of source proteins for all five HLA allotypes were similar and we observed that peptide sampling was not affected by source protein masses and lengths. Next, we examined the features of naturally presented autoantigenic peptides by class I HLA allotypes on a panel of surrogate beta

Background: Since all antihistamines are capable of crossing the blood-brain barrier, they may also cause sedation which may impair daily activities such as driving a car. The purpose of this review was to examine the effects of antihistamines on driving ability. Method: A literature search revealed 18 double-blind placebo-controlled clinical trials that applied the on-road highway driving test. In this test, subjects are instructed to drive 100-km on a public highway with a steady lateral position and a constant speed (95 km/h). Primary outcome measure is the Standard Deviation of Lateral Position (SDLP, cm), i.e. the weaving of the car. Results: The literature search yielded 18 clinical trials. At therapeutic doses, a single dose of diphenhydramine, emedastine and hydroxizine impaired driving comparable or greater than the effects of BAC 0.08%. Clemastine, triprolidine, mizolastine, acrivastine, dexchlorpheniramine CR and mequitazine impaired driving performance to the same extent as BAC 0.05%. For mizolastine significant impairment was only seen after higher than therapeutic doses. Results for cetirizine were mixed, illustrating the drug has the potential to impair driving performance, especially in sensitive subjects. Terfenadine, loratadine, levocetirizine, desloratadine, ebastine, bilastine fexofenadine and rupatadine showed no driving impairment in the standard driving test after acute administration of their recommended dose. Several studies examined subchronic effects of antihistamines on driving performance. After 4 days of daily treatment significant driving impairment was found for emedastine (2 and 4 mg bid), diphenhydramine (50 mg), clemastine (2 mg bid), triprolidine (5 mg bid), after 5 days of ebastine (30 mg), and after 8 days of hydroxyzine (50 mg). Mixed results were found for cetirizine (10 mg), terfenadine (120 mg) and loratadine (20 mg). No significant differences from placebo were observed after 4 days of subchronic treatment with triprolidine

The diagnosis of allergy and determination of the involved allergen is largely based on clinical history. Skin prick assessment and quantitation of specific IgE are supplementary tests in the overall assessment of the patient reporting an allergic reaction. We report a case of a 22 year old female with anaphylaxis characterised by urticaria, angioedema and hypotension post ingestion of a meal including cabbage. She tolerated broccoli, cauliflower, mustard and peach and reported no symptoms with latex exposure. Despite specific IgE to cabbage being negative, a skin prick test to fresh cabbage was positive. A control patient did not react to cabbage. This case is the first documentation of cabbage induced anaphylaxis with negative specific IgE but positive skin test. It highlights the limitation of in-vitro testing in the assessment of a patient with an allergic reaction. Important allergenic proteins may not be included in commercial test kits and a high index of suspicion should prompt further testing.

Encephalopathy associated with the presence of voltage-gated potassium channel (VGKC) antibodies is a rare but increasingly recognised condition that has been associated with a combination of psychological symptoms, memory loss, and seizures, hyponatraemia and chorea. While it is reported that the incidence of new cases is approaching one per million per year in the United Kingdom, the international incidence is unknown. Lumbar puncture biochemistry and magnetic resonance imaging often demonstrate suggestive findings, and the presence of VGKC antibodies in serum is diagnostic. Previously described treatment includes corticosteroids, intravenous immunoglobulin, plasmapheresis, mycophenolate mofetil, azathioprine, and rituximab. The results of long term follow up are not yet available.We present a case of successful treatment and complete functional recovery of a patient with encephalopathy associated with VGKC antibodies using steroids and rituximab.

A case report of the successful desensitisation of a four year old paediatric patient with beta thalassaemia major to deferasirox following a serious adverse skin reaction. A four year old girl with beta thalassaemia major was commenced on deferasirox 125 mg daily in May 2012. After one week she developed a widespread, erythermatous macular rash. Erythema multiforme was diagnosed. Deferasirox was ceased and the rash resolved over coming weeks. She was re-challenged the following month with deferasirox and developed angioedema of the lips and a mouth ulcer one day after re-commencement. A literature search was undertaken to identify deferasirox desensitisation case reports. One abstract was located, reporting three cases of successful deferasirox desensitisation in adults. To our knowledge there are no reported cases or protocols of deferasirox desensitisation in children in the literature. Aside from case reports, data regarding other medical desensitisation protocols in children is also limited. Immunology, thalassaemia and pharmacy departments formulated a paediatric deferasirox desensitisation schedule based on paediatric antibiotic desensitisation protocols in a recent review and the hospital adult deferasirox desensitisation protocol. The starting dose was the same as the adult protocol with the doses being increased at a slower rate and smaller increments, so that the full paediatric dose could be reached in the same time frame as the adult protocol. The child was administered deferasirox daily, with dosage approximately doubling at each dose increase over 25 days starting at 1.25 mg until target dose was reached. Each dose increase was given under close observation in hospital. The patient tolerated desensitisation and reached target dose without complications. She is successfully continuing oral deferasirox treatment. This case is the first to our knowledge of a paediatric deferasirox desensitisation and shows the potential for more use of this desensitisati

Breastfeeding anaphylaxis is a rare but potentially life threatening occurrence. There have been limited case studies documenting this rare condition. We present a case of a 35 year old pregnant lady with 3 documented anaphylaxis episodes associated with hypotension, abdominal pain and diarrhoea as well as a tryptase rise during each event. These 3 episodes occurred in her 2nd trimester with complete resolution during her 3rd. There were not associated triggers with negative RASTs to multiple food agents. She did not change her diet or activities. She commenced breastfeeding 2 days post partum with symptoms of wide spread urticaria and dizziness and thus ceased breast feeding for 2 days. On immediate commencement of breastfeeding she developed another episode of anaphylaxis, with significant hypotension requiring adrenaline. RAST test remained negative. Although there have been documented episodes of anaphylaxis while breastfeeding, pregnancy related anaphylaxis has not been well documented. We feel both occurrences may be hormone related and further research into a possible underlying hormonal trigger should be examined.

Glomerular planted antigens (histones,DNA,andC1q) arepotential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patientswith LN. Prevalent antibody isotypes were defined, levelswere determined, and glomerular colocalization was investigated. Renal and circulating antibodieswerematched, and serum levelswere compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (antia-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti a-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and antia-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria.3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.

A case report of the successful desensitisation of a four year old paediatric patient with beta thalassaemia major to deferasirox following a serious adverse skin reaction. A four year old girl with beta thalassaemia major was commenced on deferasirox 125 mg daily in May 2012. After one week she developed a widespread, erythermatous macular rash. Erythema multiforme was diagnosed. Deferasirox was ceased and the rash resolved over coming weeks. She was re-challenged the following month with deferasirox and developed angioedema of the lips and a mouth ulcer one day after re-commencement. A literature search was undertaken to identify deferasirox desensitisation case reports. One abstract was located, reporting three cases of successful deferasirox desensitisation in adults. To our knowledge there are no reported cases or protocols of deferasirox desensitisation in children in the literature. Aside from case reports, data regarding other medical desensitisation protocols in children is also limited. Immunology, thalassaemia and pharmacy departments formulated a paediatric deferasirox desensitisation schedule based on paediatric antibiotic desensitisation protocols in a recent review and the hospital adult deferasirox desensitisation protocol. The starting dose was the same as the adult protocol with the doses being increased at a slower rate and smaller increments, so that the full paediatric dose could be reached in the same time frame as the adult protocol. The child was administered deferasirox daily, with dosage approximately doubling at each dose increase over 25 days starting at 1.25 mg until target dose was reached. Each dose increase was given under close observation in hospital. The patient tolerated desensitisation and reached target dose without complications. She is successfully continuing oral deferasirox treatment. This case is the first to our knowledge of a paediatric deferasirox desensitisation and shows the potential for more use of this desensitisati

The diagnosis of allergy and determination of the involved allergen is largely based on clinical history. Skin prick assessment and quantitation of specific IgE are supplementary tests in the overall assessment of the patient reporting an allergic reaction. We report a case of a 22 year old female with anaphylaxis characterised by urticaria, angioedema and hypotension post ingestion of a meal including cabbage. She tolerated broccoli, cauliflower, mustard and peach and reported no symptoms with latex exposure. Despite specific IgE to cabbage being negative, a skin prick test to fresh cabbage was positive. A control patient did not react to cabbage. This case is the first documentation of cabbage induced anaphylaxis with negative specific IgE but positive skin test. It highlights the limitation of in-vitro testing in the assessment of a patient with an allergic reaction. Important allergenic proteins may not be included in commercial test kits and a high index of suspicion should prompt further testing.

Encephalopathy associated with the presence of voltage-gated potassium channel (VGKC) antibodies is a rare but increasingly recognised condition that has been associated with a combination of psychological symptoms, memory loss, and seizures, hyponatraemia and chorea. While it is reported that the incidence of new cases is approaching one per million per year in the United Kingdom, the international incidence is unknown. Lumbar puncture biochemistry and magnetic resonance imaging often demonstrate suggestive findings, and the presence of VGKC antibodies in serum is diagnostic. Previously described treatment includes corticosteroids, intravenous immunoglobulin, plasmapheresis, mycophenolate mofetil, azathioprine, and rituximab. The results of long term follow up are not yet available.We present a case of successful treatment and complete functional recovery of a patient with encephalopathy associated with VGKC antibodies using steroids and rituximab.

Breastfeeding anaphylaxis is a rare but potentially life threatening occurrence. There have been limited case studies documenting this rare condition. We present a case of a 35 year old pregnant lady with 3 documented anaphylaxis episodes associated with hypotension, abdominal pain and diarrhoea as well as a tryptase rise during each event. These 3 episodes occurred in her 2nd trimester with complete resolution during her 3rd. There were not associated triggers with negative RASTs to multiple food agents. She did not change her diet or activities. She commenced breastfeeding 2 days post partum with symptoms of wide spread urticaria and dizziness and thus ceased breast feeding for 2 days. On immediate commencement of breastfeeding she developed another episode of anaphylaxis, with significant hypotension requiring adrenaline. RAST test remained negative. Although there have been documented episodes of anaphylaxis while breastfeeding, pregnancy related anaphylaxis has not been well documented. We feel both occurrences may be hormone related and further research into a possible underlying hormonal trigger should be examined.

Introduction: immunoglobulin A is responsible for protecting the infections of the respiratory and gastrointestinal tracts, and selective immunoglobulin A deficiency is the most common primary humoral immunodeficiency. It is speculated that their occurrence may predispose to the development of systemic lupus erythematous.Objectives: to study the prevalence of selective immunoglobulin A deficiency in patients with juvenile systemic lupus erythematosus and compared between groups of patients with and without selective immunoglobulin A deficiency, age and clinical manifestations at diagnosis of juvenile systemic lupus erythematosus and the index of disease activity at the time of analysis IgA levels, family history of rheumatic diseases, autoimmune and / or congenital immunodeficiency’s.Patients and methods: we reviewed the medical records of 63 patients diagnosed with lupus according to the criteria of the American College of Rheumatology. Immunoglobulin A plasma levels of these patients were measured by nephelometry and were considered low when less than 70 mg/dL. Demographic data and clinical and laboratory profile, and family history were obtained by review of medical records.Results: selective immunoglobulin A deficiency was detected in 3 of 63 patients (4.8 %). The clinical and laboratory profile of selective immunoglobulin A deficiency group was not significantly different from the group without selective immunoglobulin A deficiency and it was not observed higher incidence of infections in this group of patients.Conclusion: we observed a higher prevalence of selective immunoglobulin A deficiency in patients with juvenile-onset systemic lupus erythematosus compared with the general population, with no significant differences between the clinical and laboratory profile of patients with and without selective immunoglobulin A deficiency., Introdução: a imunoglobulina A é responsável pela proteção a infecções dos tratos respiratório e gastrointestinal e a deficiência seletiva de imunoglobulina A é a imunodeficiência humoral mais comum. Especula-se que a sua ocorrência possa predispor ao desenvolvimento de lúpus eritematoso sistêmico.Objetivos: estudar a prevalência de deficiência seletiva de imunoglobulina A nos pacientes portadores de lúpus eritematoso sistêmico juvenil e comparar entre os grupos de pacientes com e sem deficiência seletiva de imunoglobulina A, a idade e manifestações clínicas à época do diagnóstico de lúpus eritematoso sistêmico juvenil; o índice de atividade da doença à época da análise dos níveis de imunoglobulina A; a história familiar de doenças reumatológicas, autoimunes e/ou imunodeficiências congênitas.Pacientes e métodos: foram revisados os prontuários de 63 pacientes com diagnóstico de lúpus eritematoso sistêmico juvenil segundo os critérios do American College of Rheumatology. Os níveis plasmáticos de imunoglobulina A destes pacientes foram dosados pelo método de nefelometria, sendo considerados baixos quando menores que 70 mg/dL. Os dados demográficos e o perfil clínico-laboratorial, além da história familiar foram obtidos através da revisão dos prontuários.Resultados: a deficiência seletiva de imunoglobulina A foi detectada em 3 dos 63 pacientes (4,8 %). O perfil clínico-laboratorial do grupo com deficiência seletiva de imunoglobulina A não foi significativamente diferente do grupo sem deficiência seletiva de imunoglobulina A, não sendo observada maior incidência de infecções neste grupo de pacientes.Conclusão: foi observada maior prevalência de deficiência seletiva de imunoglobulina A nos pacientes portadores de lúpus eritematoso sistêmico de início juvenil em comparação com a população geral, sem diferenças significativas entre o perfil clínico-laboratorial dos pacientes com e sem deficiência seletiva de imunoglobulina A.

Glomerular planted antigens (histones,DNA,andC1q) arepotential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patientswith LN. Prevalent antibody isotypes were defined, levelswere determined, and glomerular colocalization was investigated. Renal and circulating antibodieswerematched, and serum levelswere compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (antia-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti a-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and antia-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria.3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.

Late-onset neurodegenerative diseases remain poorly understood as search continues for the perceived pathogenic protein species. Previously, variants in Superoxide Dismutase 1 (SOD1) causing Amyotrophic Lateral Sclerosis (ALS) were found to destabilize and reduce net charge, suggesting a pathogenic aggregation mechanism. This paper reports analysis of compiled patient data and experimental and computed protein properties for variants of human SOD1, a major risk factor of ALS. Both stability and reduced net charge correlate significantly with disease, with larger significance than previously observed. Using two independent methods and two data sets, a probability <3% (t-statistical test) is found that ALS-causing mutations share average stability with all possible 2907 SOD1 mutations. Most importantly, un-weighted patient survival times correlate strongly with the misfolded/unfolded protein copy number, expressed as an exponential function of the experimental stabilities (R-2 = 0.31, p = 0.002), and this phenotype is further aggravated by charge (R-2 = 0.51, p = 1.8 x 10-5). This finding suggests that disease relates to the copy number of misfolded proteins. Exhaustion of motor neurons due to expensive protein turnover of misfolded protein copies is consistent with the data but can further explain e. g. the expression-dependence of SOD1 pathogenicity, the lack of identification of a molecular toxic mode, elevated SOD1 mRNA levels in sporadic ALS, bioenergetic effects and increased resting energy expenditure in ALS patients, genetic risk factors affecting RNA metabolism, and recent findings that a SOD1 mutant becomes toxic when proteasome activity is recovered after washout of a proteasome inhibitor. Proteome exhaustion is also consistent with energy-producing mitochondria accumulating at the neuromuscular junctions where ALS often initiates. If true, this exhaustion mechanism implies a complete change of focus in treatment of ALS towards actively nursing the energ

CD8+ T cell exhaustion represents a major hallmark of chronic HIV infection. Two key transcription factors governing CD8+ T cell differentiation, T-bet and Eomesodermin (Eomes), have previously been shown in mice to differentially regulate T cell exhaustion in part through direct modulation of PD-1. Here, we examined the relationship between these transcription factors and the expression of several inhibitory receptors (PD-1, CD160, and 2B4), functional characteristics and memory differentiation of CD8+ T cells in chronic and treated HIV infection. The expression of PD-1, CD160, and 2B4 on total CD8+ T cells was elevated in chronically infected individuals and highly associated with a T-betdimEomeshi expressional profile. Interestingly, both resting and activated HIV-specific CD8+ T cells in chronic infection were almost exclusively T-betdimEomeshi cells, while CMV-specific CD8+ T cells displayed a balanced expression pattern of T-bet and Eomes. The T-betdimEomeshi virus-specific CD8+ T cells did not show features of terminal differentiation, but rather a transitional memory phenotype with poor polyfunctional (effector) characteristics. The transitional and exhausted phenotype of HIV-specific CD8+ T cells was longitudinally related to persistent Eomes expression after antiretroviral therapy (ART) initiation. Strikingly, these characteristics remained stable up to 10 years after ART initiation. This study supports the concept that poor human viral-specific CD8+ T cell functionality is due to an inverse expression balance between T-bet and Eomes, which is not reversed despite long-term viral control through ART. These results aid to explain the inability of HIV-specific CD8+ T cells to control the viral replication post-ART cessation.

Background: Human rhinovirus (HRV) is the major cause of asthma attacks requiring hospitalisation in children although allergies play a part. A recently discovered strain, HRVC, is thought to be a major cause of these infections. Little is known, however, about the relative roles of the various HRV strains in childhood asthma attacks. In this study, we sought to identify HRV subtypes and their relationship to sensitization and asthma severity and subphenotypes in children admitted to hospital with asthma. Method(s): The Melbourne Air Pollen Children's and Adolescent Health (MAPCAH) study is investigating the role of pollen and its interaction with air pollutants and respiratory infections in asthma hospital admissions among children aged 2-17 years. At admission, all participants undergo nose/ throat swabs (NTS) for respiratory viruses and follow-up NTS are obtained 9 weeks after admission to assess viral shedding during the control period. Respiratory viruses are identified by multiplex PCR. PRV positive samples at are sub-typed by sequencing the VP4 and partial VP2 gene sequence of PRV. This region distinguishes between HRV and enteroviruses and differentiates all known subtypes of HRV. Result(s): Two hundred and sixty-nine children admitted with a diagnosis of asthma have been recruited. Fifty-seven females and 105 males were detected with a virus at admission. 151 (60%) were picornavirus. Of those, 30 participants who were shedding picornavirus virus at admission continued to shed it when tested 9 weeks after the admission. Compared to participants stopped shedding, those who continue to shed were more likely to be sensitized to egg and peanut 34% versus 21%, OR = 2.96, (95%CI 1.02-8.58), P = 0.04. We genotyped a subset (n = 114) of HRV specimens detected at admission. Of the HRVs detected at admission, 52% were identified as HRVC. A median of 9 weeks after the admission, retesting, detected rhinovirus in 30 of these participants, including 33% with HRVC. Among

Background: Human rhinovirus (HRV) is the major cause of asthma attacks requiring hospitalisation in children although allergies play a part. A recently discovered strain, HRVC, is thought to be a major cause of these infections. Little is known, however, about the relative roles of the various HRV strains in childhood asthma attacks. In this study, we sought to identify HRV subtypes and their relationship to sensitization and asthma severity and subphenotypes in children admitted to hospital with asthma. Method(s): The Melbourne Air Pollen Children's and Adolescent Health (MAPCAH) study is investigating the role of pollen and its interaction with air pollutants and respiratory infections in asthma hospital admissions among children aged 2-17 years. At admission, all participants undergo nose/ throat swabs (NTS) for respiratory viruses and follow-up NTS are obtained 9 weeks after admission to assess viral shedding during the control period. Respiratory viruses are identified by multiplex PCR. PRV positive samples at are sub-typed by sequencing the VP4 and partial VP2 gene sequence of PRV. This region distinguishes between HRV and enteroviruses and differentiates all known subtypes of HRV. Result(s): Two hundred and sixty-nine children admitted with a diagnosis of asthma have been recruited. Fifty-seven females and 105 males were detected with a virus at admission. 151 (60%) were picornavirus. Of those, 30 participants who were shedding picornavirus virus at admission continued to shed it when tested 9 weeks after the admission. Compared to participants stopped shedding, those who continue to shed were more likely to be sensitized to egg and peanut 34% versus 21%, OR = 2.96, (95%CI 1.02-8.58), P = 0.04. We genotyped a subset (n = 114) of HRV specimens detected at admission. Of the HRVs detected at admission, 52% were identified as HRVC. A median of 9 weeks after the admission, retesting, detected rhinovirus in 30 of these participants, including 33% with HRVC. Among

Monozygotic (MZ) twins discordant for complex diseases may help to find disease mechanisms that are not due to genetic variants. Intermittent allergic rhinitis (IAR) is an optimal disease model because it occurs at defined time points each year, owing to known external antigens. We hypothesized that MZ twins discordant for IAR could help to find gene expression differences that are not dependent on genetic variants. We collected blood outside of the season from MZ twins discordant for IAR, challenged their peripheral blood mononuclear cells (PBMC) with pollen allergen in vitro, collected supernatants and isolated CD4+ T cells. We identified disease-relevant mRNAs and proteins that differed between the discordant MZ twins. By contrast, no differences in microRNA expression were found. Our results indicate that MZ twins discordant for IAR is an optimal model to identify disease mechanisms that are not due to genetic variants., Funding Agencies|European Commission|223367|Swedish Research Council

Introduction: The Melbourne Air Pollen Children's and Adolescent Health (MAPCAH) is the fi rst asthma hospital admissions study among children and adolescents to examine pollen exposure and how it interacts with other outdoor aeroallergens, air pollutants and respiratory infections in triggering asthma. In this abstract we describe its methodology, recruitment and preliminary data. Method(s): MAPCAH is a case-cross over study of children and adolescents aged between 2 and 17 years admitted to The Royal Children's Hospital, Victoria with an asthma exacerbation. All participants undergo skin prick tests to pollens, mould, house dust mite, cat dander, hen's egg, and peanut (including Histamine and saline control), nose/throat swab (NTS) for respiratory viruses and complete a questionnaire. Follow-up NTS are obtained 6 to 8 weeks after admission to assess viral shedding during the control period. During the study period a Burkard Volumetric spore trap has been setup to collect daily airborne pollen (classifi ed as grass, tree, weed and other) and fungal spores (Cladosporium and Alternaria). Daily air pollution and meteorological data are available. Result(s): Since September 2009 we have recruited 225 children (74% recruitment rate). The most common reason for refusal to participate was causing further distress to child by testing. There were no differences in age, gender, and postcode between responders and non responders. Of these, 136 (60.4%) are male with median age 4 (range 2-16 years), 47% were sensitized to any pollen, 57% to house dust mite and 26% to egg or peanut allergens. 59 respiratory viruses were detected among children sensitized to any pollen - 57 Picorna and 2 to both Adeno and Picorna virus. No swine fl u (H1N1/2009) was detected. Conclusion(s): A high proportion of children approached participated and there was no difference between responders and non responders on sociodemographic characteristics ensuring some internally validity of the study. There

Background/Objective: Vitamin D is increasingly recognized for its role outside the endocrine and bone system, including the cardiovascular, central nervous and respiratory systems. It is also emerging as important in both innate and acquired immunity. Innate immunity includes the activation of toll like receptors (TLR), in turn leading to induction of proinfl ammatory cytokines and reactive oxygen species. Vitamin D deficiency is increasingly prevalent. This pilot, prospective longitudinal cohort, study aimed to see if Vitamin D defi ciency results in an increased innate infl ammatory signature, and whether reversal of the defi ciency results in a decreased infl ammatory state. Method(s): Participants in the study were recruited amongst staff within Southern Health. Those fulfi lling the inclusion criteria, including a Vitamin D level of <50 nmol/L, were loaded with a 50,000 units tablet of the vitamin given for 10 days. The TLR2, TLR 4 and CD86 expression on peripheral blood monocytes was measured from PBMCs collected prior to vitamin D loading and subsequently at 1 month, then 3 months post. Individual patient blood was stimulated with specific TLR ligands and the resultant supernatant assayed for TNFalpha, IL-6, IFN-a and IP-10 by ELISA. Result(s): Out of 30 patients screened, 73% were vitamin D defi cient, with levels <50 nmol/L. Of these, 11 participants showing good response to supplementation were further tested. Following stimulation with TLR ligands, the initial, Vitamin D defi cient samples, produced a number of proinfl ammatory cytokines which were signifi cantly reduced upon Vitamin D supplementation. TLR2 expression on peripheral monocytes was increased though there was no change in TLR4 or CD86. Conclusion(s): This pilot study is the fi rst in the literature to look at how peripheral innate immune responses and TLR expression are affected by Vitamin D deficiency. It has shown that this vitamin has a potentially important role in innate immunity. In th

Introduction: The Melbourne Air Pollen Children's and Adolescent Health (MAPCAH) is the fi rst asthma hospital admissions study among children and adolescents to examine pollen exposure and how it interacts with other outdoor aeroallergens, air pollutants and respiratory infections in triggering asthma. In this abstract we describe its methodology, recruitment and preliminary data. Method(s): MAPCAH is a case-cross over study of children and adolescents aged between 2 and 17 years admitted to The Royal Children's Hospital, Victoria with an asthma exacerbation. All participants undergo skin prick tests to pollens, mould, house dust mite, cat dander, hen's egg, and peanut (including Histamine and saline control), nose/throat swab (NTS) for respiratory viruses and complete a questionnaire. Follow-up NTS are obtained 6 to 8 weeks after admission to assess viral shedding during the control period. During the study period a Burkard Volumetric spore trap has been setup to collect daily airborne pollen (classifi ed as grass, tree, weed and other) and fungal spores (Cladosporium and Alternaria). Daily air pollution and meteorological data are available. Result(s): Since September 2009 we have recruited 225 children (74% recruitment rate). The most common reason for refusal to participate was causing further distress to child by testing. There were no differences in age, gender, and postcode between responders and non responders. Of these, 136 (60.4%) are male with median age 4 (range 2-16 years), 47% were sensitized to any pollen, 57% to house dust mite and 26% to egg or peanut allergens. 59 respiratory viruses were detected among children sensitized to any pollen - 57 Picorna and 2 to both Adeno and Picorna virus. No swine fl u (H1N1/2009) was detected. Conclusion(s): A high proportion of children approached participated and there was no difference between responders and non responders on sociodemographic characteristics ensuring some internally validity of the study. There

Background/Objective: Vitamin D is increasingly recognized for its role outside the endocrine and bone system, including the cardiovascular, central nervous and respiratory systems. It is also emerging as important in both innate and acquired immunity. Innate immunity includes the activation of toll like receptors (TLR), in turn leading to induction of proinfl ammatory cytokines and reactive oxygen species. Vitamin D deficiency is increasingly prevalent. This pilot, prospective longitudinal cohort, study aimed to see if Vitamin D defi ciency results in an increased innate infl ammatory signature, and whether reversal of the defi ciency results in a decreased infl ammatory state. Method(s): Participants in the study were recruited amongst staff within Southern Health. Those fulfi lling the inclusion criteria, including a Vitamin D level of <50 nmol/L, were loaded with a 50,000 units tablet of the vitamin given for 10 days. The TLR2, TLR 4 and CD86 expression on peripheral blood monocytes was measured from PBMCs collected prior to vitamin D loading and subsequently at 1 month, then 3 months post. Individual patient blood was stimulated with specific TLR ligands and the resultant supernatant assayed for TNFalpha, IL-6, IFN-a and IP-10 by ELISA. Result(s): Out of 30 patients screened, 73% were vitamin D defi cient, with levels <50 nmol/L. Of these, 11 participants showing good response to supplementation were further tested. Following stimulation with TLR ligands, the initial, Vitamin D defi cient samples, produced a number of proinfl ammatory cytokines which were signifi cantly reduced upon Vitamin D supplementation. TLR2 expression on peripheral monocytes was increased though there was no change in TLR4 or CD86. Conclusion(s): This pilot study is the fi rst in the literature to look at how peripheral innate immune responses and TLR expression are affected by Vitamin D deficiency. It has shown that this vitamin has a potentially important role in innate immunity. In th

The cytokine pattern of T lymphocytes has not been characterized in children with combinations of paediatric immunological disorders. We describe cytokine secretion in children with type 1 diabetes, coeliac disease and allergy and combinations of two of these diseases after stimulation with 'disease-specific' antigens. Peripheral blood mononuclear cells (PBMC) were collected from 68 children with type 1 diabetes, allergy or coeliac disease, two of these diseases in combination or none of these diseases. Using the enzyme-linked immunospot (ELISPOT) technique, interferon (IFN)-γ and interleukin (IL)-4 were analysed from fresh PBMC spontaneously and after in vitro stimulation with antigens associated with one or more of these diseases (insulin, gluten, birch and cat extract, β-lactoglobulin, ovalbumin and phytohaemagglutinin) in order to divide T helper (Th)1- from Th2-like lymphocytes. Stimulation with birch and cat extract caused increased IL-4 secretion in allergic children. A low IFN-γ response to insulin was found in type 1 diabetic children, whereas allergic children responded to insulin by increased IL-4 secretion. Children suffering from both type 1 diabetes (Th1-prone) and allergy (Th2-prone) reacted distinctly to general mitogen stimulation. Children suffering from two Th1-dominated diseases (type 1 diabetes and coeliac disease) showed hardly any response to either food or inhalation allergens. Our results indicate an important interplay between common immunological diseases in children. The combination of two Th1-deviated diseases is associated with a suppressed immune response, whereas a combination of Th1- and Th2-dominated diseases appears to increase the general immune response. © 2006 The Author(s).

Background: No strawberry allergen has so far been identified and characterized. Methods: Serum samples were collected from patients with a suggestive case history of adverse reactions to strawberry and other fruits. Extracts from fresh and frozen strawberries were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting and mass spectrometry. Patient blood samples were analysed for inhibition of IgE binding and basophil degranulation. Results: Several IgE-binding proteins could be detected. In more than half of the patient sera, a 20/18-kDa doublet band was observed in Western blotting. These two bands were excised and analysed by mass spectrometry showing the presence of proteins belonging to the Bet v 1 family of allergens. Inhibition of the IgE binding to the 20/18-kDa doublet was obtained by addition of two recombinantly expressed allergens belonging to the Bet v 1 family (Bet v 1 and Mal d 1) and strawberry protein extract. In a cell-based assay of patient blood samples, basophil degranulation could be induced by strawberry protein extract and by Bet v 1 and Mal d 1. Conclusions: We conclude that strawberry homologues to Bet v 1 may be allergens of importance for adverse reactions to strawberry.