Evaluation of Quality of Life of Adult Patients with Celiac Disease in Argentina: From Questionnaire Validation to Assessment.

This cross-sectional study aimed to translate, culturally adapt, validate, and apply a Celiac Disease Quality of Life (CD-QoL) questionnaire to a representative sample of Argentina's celiac population. A previously developed and validated questionnaire (Celiac Disease Questionnaire: CDQ) was chosen as a tool for assessing the health-related quality of Life (HRQoL) of adult celiac patients in Argentina. Therefore, the study was performed in four stages: (a) translation and re-translation of the CDQ to Argentinian-Spanish language; (b) cultural adaptation and semantic evaluation; based on the Delphi method (c) validation of the CDQ by applying it to a representative sample of Argentinian celiac patients; (d) statistical analysis of the data. The result of stages (a) and (b) was a translated and culturally adapted an Argentinian-Spanish version of the CDQ, which was generated after reaching consensus between the corresponding four (phase a) and 10 (phase b) professionals involved in the different phases of this process. Among them, we can cite bilingual healthcare professionals with extensive experience in research and celiac disease, celiac patients, gastroenterologists, general practitioners, dieticians, and psychologists. The resulting CDQ proved to be an appropriate measuring tool to assess the HRQoL of Argentinian celiac patients confirmed by a good fit in the confirmatory factor validity analysis (RMSEA < 0.001 and χ2 = 267.325, df = 313, p = 0.971) and high values of internal consistency (Cronbach's alpha > 0.7). A total of 191 participants accessed the questionnaire, and 171 individuals from 20 out of 23 Argentinian states completed the questionnaire. There was no correlation between higher educational level nor marital status with QoL. Individuals on a strict gluten-free diet (GFD) and those who do not take antidepressants showed higher QoL. Male gender also presented better HRQoL. There was no correlation between differences in HRQoL and age of the respondent, age at diagnosis, symptoms at diagnosis, or having other chronic diseases. However, a significantly higher score of HRQoL was reported among those individuals who disclosed having knowledge of CD related national regulations and benefits. This study highlights the importance of maintaining current public health regulations that support chronic disease patients, such as celiac patients.

Clinical Manifestations of Kawasaki Disease at Different Age Spectrum: A Ten-Year Study.

Background and objectives: The present study is the first known in Latin America to enroll a substantial number of Kawasaki disease (KD) patients with an extended follow-up. This study aimed to: (1) to expose the difficulties and delays in the diagnosis of KD in a developing country, (2) to describe and correlate the clinical features of this disorder with the children's age at the time of disease onset, (3) to correlate the frequent lack of early diagnosis with a delayed application of appropriate treatment, and (4) to describe the outcome and eventual recurrences of KD in our region. Materials and Methods: Three hundred and one participants (183 males and 118 females) included in the study were diagnosed and, subsequently, clinically followed for ten years (January 2007 to December 2016) at the Pediatric Rheumatology Walk-in Clinic of the Children's Hospital of Brasilia. Results: Episodes ranged from four months to two years. This rate of recurrence was well-above that disclosed by previous reports. Delay in diagnosis, in all age groups, caused an undesirable delay between the disease onset, the final diagnosis, and the administration of intravenous immunoglobulin (IVIG). KD recurred in 25 (8.3%) of the children during the first three years of follow-up. In seven patients, KD recurred twice, with an interval between episodes ranging from four months to two years. Conclusions: This rate of recurrence was well-above that disclosed by previous reports. In Latin America, aside from a handful of physicians and researchers, KD is being ignored. There is a pressing need to educate primary health care physicians and bring awareness to the fact that KD is not an exotic condition that affects only the Asian populations but a disorder that already exists among us and that frequently results in severe consequences.

Quality of Life of Celiac Patients in Brazil: Questionnaire Translation, Cultural Adaptation and Validation.

(1) Background: Celiac disease (CD) is a common autoimmune disorder. The manifestations of the disease and the obligatory life-long gluten-free diet (GFD) are associated with the impairment of patients' quality of life. Therefore, the present study aimed to translate, culturally adapt and validate a celiac disease quality of life (CD-QoL) questionnaire and apply it to a representative number of Brazilian CD patients. (2) Methods: A cross-cultural Brazilian-Portuguese version of the CD-QoL was developed according to revised international guidelines. The questionnaire was administered to 450 celiac patients. The reliability, reproducibility and validity were studied. (3) Results: The Brazilian CD-QoL questionnaire presents valid measures of reproducibility and internal consistency. Early diagnosis is related to higher scores of Brazilian CD-QoL social, sub- and total scale. There was a positive correlation between higher education level and higher QoL. Individuals with partners tend to have a better emotional subscale of QoL. CD-patients who follow a strict GFD have highest QoL scale values. Men scored higher than women on the CD-QoL. All results were statistically significant except for the gastrointestinal subscale. (4) Conclusions: Brazilian CD-QoL allows comparative research between different celiac populations in the world. QoL research will help in the development of effective strategies to improve Brazilian celiac patients' quality of life.

Frequency of HLA-DQ, susceptibility genotypes for celiac disease, in Brazilian newborns.

BACKGROUND: The frequency of HLA-DQ2 and DQ8 predisposing genotypes for celiac disease (CD) has shown significant variation among different world regions and has not been previously determined among the highly interbred Brazilian population. The aim of this study was to investigate the frequency of these genotypes among Brazilian newborns (NB). METHODS: We typed DQA1*05 - DQB1*02 (DQ2.5) and DQA1*03 - DQB1*03:02 (DQ8) alleles in 329 NB using qPCR technique. Subsequently we confirmed our results by PCR-SSP using a reference kit which further identified DQ2.2 (DQA1*02:01 - DQB1*02). RESULTS: Among the 329 NB, using qPCR technique: 5 (1.52%) carried both DQ2.5 and DQ8 variants; 58 (17.63%) carried only DQ2.5 (DQA1*05 and DQB1*02) and 47 (14.29%) carried only the DQ8 (DQA1*03 and DQB1*03:02) variant. The use of the PCR-SSP method yielded further information; among the 329 samples: 34 (10.34%) tested positive for DQ2.2 and among the 47 previously DQ8 positives samples, we found 10 (3.04%) that also tested positives for DQ2.2. CONCLUSION: 43.7% of the analyzed individual tested positive for at least one of the CD predisposing HLA-DQ genotypes in our group of Brazilian NB. The highest frequency was found for DQ2.5 positive subjects (17.6%) followed by DQ8 (11.3%); DQ2.2 (10.3%); DQ8 and DQ2.2 (3.0%); DQ2.5 and DQ8 (1.5%). We found no positive sample for DQ2.5 associated with DQ2.2.

PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN.

BACKGROUND: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. OBJECTIVE: The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. METHODS: HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. RESULTS: In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. CONCLUSION: The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

Prevalência de genótipos predisponentes para doença celíaca, incluindo HLA-DQ2. 2, em crianças brasileiras / Prevalence of celiac disease predisposing genotypes, including hla-dq2. 2 variant, in brazilian children

ABSTRACT BACKGROUND: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. OBJECTIVE: The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. METHODS: HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. RESULTS: In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. CONCLUSION: The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

RESUMO CONTEXTO: A doença celíaca é uma enteropatia autoimune, desencadeada pela ingestão do glúten em indivíduos geneticamente predispostos. Quase todos os pacientes celíacos possuem genes que codificam os heterodímeros HLA-DQ2.5 e DQ8. Nos últimos anos, mesmo com algumas controvérsias a respeito, tem se dado grande importância ao HLA-DQ2.2 como outra provável variante predisponente para doença celíaca. OBJETIVO: O objetivo do nosso trabalho foi determinar a provável associação entre HLA-DQ2.2 e a doença celíaca em crianças brasileiras, mediante a análise da prevalência das variantes predisponentes para doença celíaca em um grupo representativo desta população que ainda carece de dita informação. MÉTODOS: A genotipagem das variantes HLA-DQ foi realizada em populações de crianças celíacas (n=100) e não celíacas (n=110). A presença das seguintes variantes foi testada em todas as amostras: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) e DQA1*02:01-DQB1*02:02 (DQ2.2). A análise estatística foi realizada utilizando o teste exato de Fisher. RESULTADOS: No grupo de 100 crianças celíacas, 78 (78%) foram positivas para DQ2, 13 (13%) para DQ2/DQ8 e 6 (6%) foram DQ8 positivas. O padrão de variantes predisponentes no grupo de 110 crianças não celíacas foi: 33 (29.9%) amostras positivas para DQ2, 2 (1.8%) DQ2/DQ8 positivas e 15 (13.6%) DQ8 positivas. Quando as prevalências de ambos grupos foram compradas, foram achadas diferenças significativas entre algumas, mas não todas as variantes predisponentes. CONCLUSÃO: A genotipagem das variantes HLA-DQ predisponentes para doença celíaca mostrou um padrão similar ao achado em populações europeias e não-europeias, o qual pode ser resultado da miscigenação que deu origem à população brasileira atual. Nosso trabalho não mostrou associação significativa entre a variante DQ2.2 e a doença celíaca na população estudada.

The possible link between coeliac and Kawasaki diseases in Brazil: a cross-sectional study.

BACKGROUND: Kawasaki disease (KD) is a self-limited acute systemic vasculitis of unknown aetiology that predominantly affects infants and young children eventually associated with immunological abnormalities. Coeliac disease (CD) is an inflammatory autoimmune disease characterised by a permanent gluten intolerance, which affects genetically susceptible individuals of any age group, and can cause intestinal and systemic symptoms. Association of CD with KD has been previously described in a single study that disclosed a surprisingly high prevalence of CD in children with a history of KD. OBJECTIVE: To confirm the existence of a higher prevalence of CD among individuals with a history of KD, which would turn the screening for CD in patients with history of KD highly advisable. SETTING: Children with history of KD, diagnosed and followed at the Rheumatology Clinic of the Children's Hospital of Brasilia (Brasilia, Brazil). PARTICIPANTS: This study included 110 children with history of KD and a control group composed of 110 presumably healthy children. INTERVENTIONS: Participants underwent anti-transglutaminase and anti-endomysial antibodies tests and genetic typing for the presence of CD predisposing alleles (HLA-DQ2 and DQ8). Jejunal biopsy was performed when necessary, according the European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines. RESULTS: Diagnosis of CD was confirmed in one (0.91%) patient with KD by positive serological tests, presence of predisposing alleles and CD typical lesions on duodenal biopsy. All serological tests were negative among the controls. The prevalence of CD predisposing alleles among patients with KD was 29.09%, similar to the prevalence found among controls, 33.64%. CONCLUSION: The detected CD prevalence (0.91%) does not confirm the existence of an association between KD and CD since this prevalence is similar to that found in the general population (≃1%).

Using niche-modelling and species-specific cost analyses to determine a multispecies corridor in a fragmented landscape.

Misiones, Argentina, contains the largest remaining tract of Upper Paraná Atlantic Forest ecoregion; however, ~50% of native forest is unprotected and located in a mosaic of plantations, agriculture, and pastures. Existing protected areas are becoming increasingly isolated due to ongoing habitat modification. These factors, combined with lower than expected regional carnivore densities, emphasize the need to understand the effect of fragmentation on animal movement and connectivity between protected areas. Using detection dogs and genetic analyses of scat, we collected data on jaguars (Panthera onca), pumas (Puma concolor), ocelots (Leopardus pardalis), oncillas (Leopardus tigrinus), and bush dogs (Speothos venaticus) across habitats that varied in vegetation, disturbance, human proximity, and protective status. With MaxEnt we evaluated habitat use, habitat suitability, and potential species richness for the five carnivores across northern-central Misiones, Argentina. Through a multifaceted cost analysis that included unique requirements of each carnivore and varying degrees of overlap among them, we determined the optimal location for primary/secondary corridors that would link the northern-central zones of the Green Corridor in Misiones and identified areas within these corridors needing priority management. A secondary analysis, comparing these multispecies corridors with the jaguar's unique requirements, demonstrated that this multispecies approach balanced the preferences of all five species and effectively captured areas required by this highly restricted and endangered carnivore. We emphasize the potential importance of expanding beyond a single umbrella or focal species when developing biological corridors that aim to capture the varied ecological requirements of coexisting species and ecological processes across the landscape. Detection dogs and genetic analyses of scat allow data on multiple species to be collected efficiently across multiple habitat types independent of the degree of legal protection. These data used with multifocal GIS analyses balance the varying degree of overlap and unique properties among them allowing for comprehensive conservation strategies to be developed relatively rapidly. Our comprehensive approach serves as a model to other regions faced with habitat loss and lack of data. The five carnivores focused on in our study have wide ranges, so the results from this study can be expanded and combined with surrounding countries, with analyses at the species or community level.

Presence of DQ2.2 Associated with DQ2.5 Increases the Risk for Celiac Disease.

Background. Celiac disease (CD) is a genetically determined immune-mediated disorder in which gluten immunogenic peptides are presented to CD4 T cells by HLA-DQ2.5, DQ8, DQ2.2, and their combinations. Our aim is to establish a risk gradient for celiac disease based on HLA-DQ profile in a brazilian representative population and the relevance of DQ2.2 in celiac disease development. Materials and Methods. 237 celiac patients and 237 controls (both groups with 164 females and 73 males) were included. All samples were tested for the presence of predisposing HLA-DQ alleles using the PCR-SSP method. Results were considered significant when p < 0.05. Disease risk was expressed as 1 : N for each HLA-DQ category described at this study. Results. DQ2.5 and/or DQ8 were detected in 224 celiac patients (94.5%) and 84 controls (35.4%). Eight celiac patients (3.4%) and 38 controls (16%) disclosed only DQ2.2. Even though DQ2.2 (ß2/ß2 or ß2/x) showed a low CD risk of 1 : 251 and 1 : 550, respectively, the genotype DQ2.5/DQ2.2 (ß2/ß2) showed high CD risk of 1 : 10 (p < 0.0001). The disease risk gradient ranged from 1 : 3014 to 1 : 7. Conclusion. Our study allowed the determination of a risk gradient for celiac disease development in at-risk population, showing that DQ2.2 variant was relevant when associated with DQ2.5.

Simplifying celiac disease predisposing HLA-DQ alleles determination by the real time PCR method.

BACKGROUND: Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Genetic susceptibility is associated with two sets of alleles, DQA1*05 - DQB1*02 and DQA1*03 - DQB1*03:02, which code for class II MHC DQ2 and DQ8 molecules, respectively. Approximately 90%-95% of celiac patients are HLA-DQ2 positive, and half of the remaining patients are HLA-DQ8 positive. In fact, during a celiac disease diagnostic workup, the absence of these specific DQA and DQB alleles has a near perfect negative predictive value. OBJECTIVE: Improve the detection of celiac disease predisposing alleles by combining the simplicity and sensitivity of real-time PCR (qPCR) and melting curve analysis with the specificity of sequence-specific primers (SSP). METHODS: Amplifications of sequence-specific primers for DQA1*05 (DQ2), DQB1*02 (DQ2), and DQA1*03 (DQ8) were performed by the real time PCR method to determine the presence of each allele in independent reactions. Primers for Human Growth Hormone were used as an internal control. A parallel PCR-SSP protocol was used as a reference method to validate our results. RESULTS: Both techniques yielded equal results. From a total of 329 samples the presence of HLA predisposing alleles was determined in 187 (56.8%). One hundred fourteen samples (61%) were positive for a single allele, 68 (36.3%) for two alleles, and only 5 (2.7%) for three alleles. CONCLUSION: Results obtained by qPCR technique were highly reliable with no discordant results when compared with those obtained using PCR-SSP.

Simplifying celaac disease predisposing hla-dq lleles determination by the reaal time pcr method / Simplificação da detecção dos alelos HLA-DQ predisponentes para doença celíaca pelo método de PCR em tempo real

Background Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Genetic susceptibility is associated with two sets of alleles, DQA1*05 - DQB1*02 and DQA1*03 - DQB1*03:02, which code for class II MHC DQ2 and DQ8 molecules, respectively. Approximately 90%-95% of celiac patients are HLA-DQ2 positive, and half of the remaining patients are HLA-DQ8 positive. In fact, during a celiac disease diagnostic workup, the absence of these specific DQA and DQB alleles has a near perfect negative predictive value. Objective Improve the detection of celiac disease predisposing alleles by combining the simplicity and sensitivity of real-time PCR (qPCR) and melting curve analysis with the specificity of sequence-specific primers (SSP). Methods Amplifications of sequence-specific primers for DQA1*05 (DQ2), DQB1*02 (DQ2), and DQA1*03 (DQ8) were performed by the real time PCR method to determine the presence of each allele in independent reactions. Primers for Human Growth Hormone were used as an internal control. A parallel PCR-SSP protocol was used as a reference method to validate our results. Results Both techniques yielded equal results. From a total of 329 samples the presence of HLA predisposing alleles was determined in 187 (56.8%). One hundred fourteen samples (61%) were positive for a single allele, 68 (36.3%) for two alleles, and only 5 (2.7%) for three alleles. Conclusion Results obtained by qPCR technique were highly reliable with no discordant results when compared with those obtained using PCR-SSP. .

Contexto Doença celíaca é uma enteropatia autoimmune desencadeada pela ingestão de gluten em indivíduos geneticamente suscetíveis. Essa suscetibilidade genética está associada a dois conjuntos de alelos, DQA1*05 - DQB1*02 e DQA1*03 - DQB1*03:02, que codificam moléculas MHC de classe II DQ2 e DQ8, respectivamente. Aproximadamente 90%-95% dos pacientes celíacos são HLA-DQ2 positivos, e metade dos restantes são HLA-DQ8 positivos. No diagnóstico da doença celíaca, a ausência desses alelos DQA e DQB específicos possui um elevado valor preditivo negativo. Objetivo Nosso objetivo foi melhorar a detecção de alguns alelos predisponentes para doença celíaca, combinando a simplicidade e sensibilidade da técnica de PCR em tempo real (qPCR) e análise da curva de melting com a especificidade dos primers de sequência específica. Métodos Primers de sequência específica para DQA1*05 (DQ2), DQB1*02 (DQ2), e DQA1*03 (DQ8) foram usados para testar a presença de cada alelo em reações independentes. Primers para Hormônio de Crescimento Humano foram usados como controle interno. Em paralelo, foi usado um protocolo de PCR-SSP como um método de referência para validar nossos resultados positivos. Resultados Das 329 amostras testadas, 187 (56.8%) foram positivas para os alelos HLA predisponentes, usando as duas técnicas. Essas 187 amostras positivas foram subdivididas em 114 (61.0%) positivas para apenas um alelo, 68 (36.3%) para dois alelos e apenas 5 (2.7%) para os três alelos. Conclusão Os resultados obtidos pela técnica de qPCR mostraram-se altamente confiáveis, sem resultados discordantes quando comparados àqueles obtidos pelo método PCR-SSP. .