Lorete Maria da Silva Kotze

Doença celíaca em crianças e adolescentes com síndrome de Down

OBJETIVOS: Alta prevalencia de doenca celiaca em pacientes com sindrome de Down tem sido descrita em varios paises. No entanto, no Brasil ainda nao ha relatos mostrando essa associacao. O presente estudo teve como objetivo avaliar a prevalencia de doenca celiaca em criancas e adolescentes com sindrome de Down no sul do Brasil. METODOS: Setenta e um pacientes (32 do sexo feminino e 39 masculino, 2-18 anos) provenientes de Curitiba, Brasil, foram estudados. Oitenta individuos (42 do sexo masculino e 38 feminino, 2-19 anos) foram utilizados como controles do estudo. Todas as amostras foram investigadas para anticorpo anti-endomisio (EmA) e anti-transglutaminase tecidual (anti-tTG). O EmA foi pesquisado atraves de imunofluorescencia indireta usando cordao umbilical como substrato e o anti-tTG atraves da tecnica de ELISA, utilizando transglutaminase tecidual como antigeno. As dosagens de IgA foram realizadas por turbidimetria. RESULTADOS: Cinco pacientes com sindrome de Down (7%) foram positivos para EmA-IgA, com titulos entre 1/5 e 1/80 e catorze (17,5%) para anti-tTG (21-340 unidades). Todos os pacientes positivos para EmA apresentaram simultaneamente positividade para o anti-tTG. Os achados clinicos e histologicos na mucosa intestinal confirmaram doenca celiaca em quatro pacientes. O outro paciente EmA positivo nao foi submetido a biopsia duodenal. Os pacientes positivos apenas para anti-tTG apresentaram valores limitrofes (< 25 unidades) e eram assintomaticos. Nenhum individuo do grupo controle foi positivo para EmA ou anti-tTG. Nenhuma amostra do estudo foi deficiente para IgA. CONCLUSOES: Os dados do presente estudo mostram alta prevalencia (5,6%) de doenca celiaca confirmada em criancas e adolescentes com sindrome de Down da regiao sul do Brasil.

Spectrum of autoantibodies in celiac patients and relatives

The coexistence of celiac disease together with a range of autoimmune disorders has already been reported. The aims of this study were to perform a broad spectrum of autoantibodies in celiac patients (N = 56), their first-degree relatives (N = 118), and compare the data with healthy controls (N = 101) and patients with inflammatory bowel disease (N = 42; Crohns disease, N = 18 and ulcerative colitis, N = 24). All serum samples were tested by indirect immunofluorescence to the anti-endomysium antibodies (EmA), anti-neutrophil cytoplasmic (ANCA), anti-smooth-muscle (SMA), anti-mitochondrial (AMA), anti-nuclear (ANA), anti-liver–kidney microsomal (LKM), anti-gastric parietal cells (GPCA), and anti-thyroid microsome (TMA). EmA were detected in 100% of celiac patients ingesting gluten and in 16.1% of the first-degree relatives, while ANCA were positive only in patients with ulcerative colitis (45.6%) and Crohns disease (16.5%). Fourteen CD patients (25%) were positive for at least one of the other autoantibodies, with significant prevalence of TMA, ANA, and GPCA, while the relatives showed 17.8% of positivity, with an increased prevalence of ANA and TMA. These results emphasize the value of screening for different autoantibodies in celiac patients and their relatives and corroborate the need for evaluation and follow-up of these individuals.

Thyroid disorders in Brazilian patients with celiac disease.

Introduction/Aim: Patients with celiac disease (CD) can develop a gluten related autoimmune disorder that affects not only the small intestine but other tissues as well. An increased prevalence of autoimmune diseases has been reported, particularly autoimmune thyroiditis. The aim of this study was to characterize thyroid disorders in patients with CD. Patients/Methods: Fifty-two patients with CD (43 female, 9 male; mean age, 41.1 years) were studied. Nine were on a gluten-free diet (GFD). They were divided into four groups: Group 1, without thyroid involvement (n = 30); Groups 2A-C, with thyroid involvement (n = 22); Group 2A, subclinical hypothyroidism (n = 11); Group 2B, clinical hypothyroidism (n = 10); and Group 2C, other thyroid disorders (n = 1). CD was confirmed by serologic and histologic criteria. Thyroid involvement was detected by measurement of thyroid stimulating hormone (TSH) and anti-thyroperoxidase antibodies (anti-TPO). Results: Increased levels of TSH and/or anti-TPO levels were detected in Groups 2A (21.1%) and 2B (19.2%). The patients of Group 2B presented clinical symptoms of hypothyroidism before the diagnosis of CD, and 5 of these patients were receiving levothyroxine. One woman (Group 2C; 1.92%) had a medullary carcinoma. There was statistical significance between the age when thyroid disease was diagnosed (current age) and the age of CD diagnosis between Groups 1 and 2B. Patients with thyroid involvement presented associated diseases such as diabetes mellitus (2), Downs syndrome (2), ulcerative colitis (1), and dermatitis herpetiformis (2). Conclusions: Our findings demonstrated an increased prevalence of thyroid disorders (hypothyroidism, 19.2%; and subclinical hypothyroidism, 21.2%), and other associated diseases in celiac patients, even on a GFD, increasing with the age of the patients. Screening for associated diseases is recommended for patients with CD, independent of age at diagnosis or treatment duration.

IgA class anti-endomysial and anti-tissue transglutaminase antibodies in relation to duodenal mucosa changes in coeliac disease

Aim: The aim of the present study was to correlate the serological methods of coeliac disease diagnostic tests (IgA EmA and IgA anti‐tTG) with the histological findings of the duodenal mucosa. Methods and Results: Forty‐seven patients were studied and the data were analysed by the Pearson correlation. Seven patients (15%) with normal mucosa were negative for both assays. Forty untreated patients showed 89% agreement between the two serological methods, with all samples (40/40) positive to EmA and 80% (32/40) positive to anti‐tTG. Eight positive samples to EmA, that were negative to anti‐tTG, presented an increased number of intra‐epithelial lymphocytes in the duodenal biopsy and clinical improvement with a gluten‐free diet. Partial or total villous atrophy was detected with EmA titres equal to or higher than 1/10. The correlation coefficient between the two serological methods was R=0.797. Conclusions: Both serological tests correlated very well with histological findings in negative patients and in those with high levels of antibodies. For patients with clinical evidence of CD but with low levels of antibodies, the combination of serological tests and intestinal biopsy is recommended.

Celiac disease in Brazilian patients: associations, complications and causes of death. Forty years of clinical experience

CONTEXT Celiac disease is a multisystem auto-immune disorder and may start at any age in genetically predisposed individuals. OBJECTIVE To identify associations, complications, and cause of death in Brazilian patients. METHODS One hundred and fifty-seven patients were studied: 23 adolescents and 134 adults, 79.6% females, 20.4% males, 75.8% at the time of diagnosis and 24.2% on a gluten-free diet, follow-up between 1 and 40 years. The diagnosis of celiac disease was based on histologic findings and the presence of serologic auto-antibodies markers for celiac disease. Specific tests were done according to clinical suspicion of associations. Bone mineral density was determined by dual energy x-rays in 53 patients upon diagnosis. The data regarding associations, complications, and causes of death were obtained by interviews and from the patients charts. RESULTS Associations: atopy (22.3%), depression (17.2%), thyroid disorder (15.9%), dermatitis herpetiformis (11.5%), diabetes mellitus types 1 and 2 (4.5%) and tumors (4.5%). COMPLICATIONS Anemia and osteopenia/osteoporosis in all groups; increased number of spontaneous abortion. Four patients (4.5%) died (one from lymphoma, one with diabetes type 1, one from acute meningitis and one due to suicide). CONCLUSIONS This experience is similar to those described in the world literature. Celiac disease presents the same characteristics independently of the geographic region. We recommend periodic evaluations, from childhood, independent of the duration of the diet. The key is to establish an interval between evaluations.

DERMATITIS HERPETIFORMIS, THE CELIAC DISEASE OF THE SKIN!

Gluten-related diseases were recently classified into three groups according to their physiopathological mechanisms: autoimmunity (celiac disease, dermatitis herpetiformis, gluten ataxia), allergy (wheat allergyrespiratory, alimentary, contact urticary and WDEIA) and no-autoimmune no-allergic (gluten sensitivity)(30). Dermatitis herpetiformis (DH) is an autoimmune blistering cutaneous disease that appears as a consequence of gluten intolerance. There is evidence that DH should be considered as the specific phenotypic cutaneous expression of a gluten-sensitive enteropathy indistinguishable from celiac disease (CD)(36). Immunological studies demonstrated the presence of granular deposits of IgA along the dermal-epidermal junction(32). DERMATITIS HERPETIFORMIS, THE CELIAC DISEASE OF THE SKIN!

Comparação dos anticorpos anti-reticulina e antiendomísio classe IGA para diagnóstico e controle da dieta na doença celíaca

Sensibility to gluten is a condition with high immunological reaction against gluten proteins from wheat, barley, rye and oats in individuals genetically susceptible. Celiac disease is its most frequent expression with various forms of clinical presentation. The treatment consists in gluten free diet. Although the biopsy of proximal small bowel is necessary, the importance of serological tests is increasing in the screening, diagnosis and monitoring of gluten free diet in celiac patients. The aim of this study was to investigate the presence of antiendomysium (EmA-IgA) and anti-reticulin (ARA-IgA) antibodies in 56 celiac patients (17 at diagnosis, 24 adherent to the diet and 15 with transgression to the diet). The antibodies were detected by indirect immunofluorescence, using human umbilical cord as substrate for the EmA-IgA and rat liver and kidney for the ARA-IgA. In the patients at diagnosis and in the group with transgression to the diet the total positivity was 100% for EmA-IgA and 59.4% for ARA-IgA. Antibodies were not detected in gluten-free diet patients. Among the 32 positive patients, the concordance of both tests was of 59.4% (19/32), being 40.6% (13/32) negative to ARA-IgA and positive to EmA-IgA. No patient was positive for ARA-IgA and negative for EmA-IgA. Thus, the sensitivity for EmA-IgA was of 100% and 59.4% for ARA-IgA. The association of the two tests did not improve the positivity in the samples. In conclusion, EmA-IgA can be considered the best serological test for diagnosis and follow up of celiac patients, because it presents high predictive value, high specificity and sensibility and is not expensive if using human umbilical cord as substrate.Sensibilidade ao gluten e um estado de elevada resposta iamunologica (celular e humoral) a ingestao de proteinas do gluten do trigo, centeio, cevada e aveia, em individuos geneticamente predispostos. A doenca celiaca e sua expressao mais frequente, variando as formas de apresentacao. Tem como tratamento a exclusao de alimentos contendo as gliadinas toxicas. Embora a biopsia do intestino delgado proximal seja necessaria, tem-se ressaltado a importância de testes sorologicos no rastreamento, diagnostico e monitorizacao da dieta isenta de gluten em pacientes com doenca celiaca. O objetivo do presente estudo foi investigar a presenca dos anticorpos antiendomisio (EmA-IgA) e anti-reticulina (ARA-IgA) em 56 pacientes celiacos (17 recem diagnosticados; 24 aderentes a dieta; 15 com transgressao a dieta). Os anticorpos foram detectados por imunofluorescencia indireta, utilizando como substrato cordao umbilical humano para os EmA-IgA, figado e rim de rato para os ARA-IgA. Nos pacientes recem diagnosticados e no grupo com transgressao a dieta houve positividade total de 100% para os EmA-IgA e 59,4% para ARA-IgA. Nos pacientes aderentes a dieta nenhum dos anticorpos foi detectado. Dentre os 32 pacientes positivos, a concordância foi de 59,4% (19), sendo que 40,6 % (13/32) eram ARA-IgA negativo e EmA-IgA positivo. Nenhum paciente mostrou-se positivo para os ARA-IgA e negativo para os EmA-IgA. Portanto, a sensibilidade para os EmA-IgA foi de 100% e de 59,4% para os ARA-IgA. A associacao dos dois testes nao aumentou os indices de positividade total nas amostras. Conclui-se que, atualmente, a pesquisa dos EmA-IgA pode constituir teste sorologico de escolha, seja para diagnostico, seja para seguimento dos pacientes celiacos, pelo alto valor preditivo, alta sensibilidade e especificidade e relativo baixo custo quando se utiliza cordao umbilical humano como substrato.

Antibodies anti-Saccharomyces cerevisiae (ASCA) do not differentiate Crohn's disease from celiac disease.

CONTEXT Anti-Saccharomyces cerevisiae antibodies (ASCA), considered serologic markers for Crohns disease, were described in patients with celiac disease, disappearing after a gluten-free diet. OBJECTIVES Evaluation of ASCA positivity in patients with Crohns disease and celiac disease in relation to healthy individuals. METHODS A total of 145 individuals were studied: 36 with Crohns disease and 52 with celiac disease, that fulfilled the diagnostic criteria for both affections, and 57 healthy individuals for control. The celiac patients were divided as follow: group CeD I at diagnosis (n = 34), group CeD II with gluten-free diet compliance (n = 13) and group CeD III with transgressions to the diet (n = 5). ASCA IgA and IgG were determined by ELISA. RESULTS With statistical significance, ASCA IgA were positive in Crohns disease, celiac disease at diagnosis and celiac disease with diet transgressions; ASCA IgG in Crohns disease and in all groups with celiac disease. CONCLUSIONS The detection of ASCA in patients with celiac disease allows to suggest that ASCA is not a specific marker for Crohns disease, but was associated with the inflammation of the small intestine. The increased levels of positive ASCA may be due to genetic factors and increased intestinal permeability.

Triagem sorológica de familiares de pacientes com doença celíaca: anticorpos anti-endomísio, antitransglutaminase ou ambos?

BACKGROUND Celiac disease is the most common intestinal disorder of caucasian populations and presents a prevalence of 8% to 18% between the relatives of patients. The anti-endomysial (IgA-EmA) and anti-tissue transglutaminase antibodies (IgA-tTG) have represented an important non invasive and sensitivity method of screening and diagnosis of celiac disease in risk groups and populations. AIM To investigate the prevalence of IgA-EmA and IgA-tTG antibodies in relatives of celiac patients and verify the degree of concordance between them. METHODS One hundred and seventy seven relatives of celiac patients (76(feminino); 101(masculino); 2-79 years) and 93 healthy individuals were evaluated (34(feminino); 59(masculino); 2-71 years). IgA-EmA were detected by indirect immunofluorescence, with human umbilical cord as substrate, while anti-IgA-tTG titers were measured by enzyme-linked immunosorbent assay (ELISA), using commercial kit. RESULTS Total positivity to antibodies in relatives of celiac patients was of 21% (37/177), and showed significant difference compared to control group (0%; 0/93). Twelve percent (21/177) of celiac disease relatives were positive to IgA-EmA, 13.56% (24/177) to IgA-tTG, and 4.52% (8/177) to both assays simultaneously. The concordance between both methods was 83.6% (148/177) and the discordance was 16.4% (29/177), with a positive and significant correlation (r = 0.435). Among the concordant results, 79.1% (140/177) were negative and 4.52% (8/177) were positive to both antibodies. Among the discordant results, 7.34% (13/177) were positive to IgA-EmA and negative to IgA-tTG, while 9.04% (16/177) were negative to IgA- EmA and positive to IgA-tTG. CONCLUSION Although the high positivity to IgA-EmA and IgA-tTG emphasizes the importance of the serological screening in relatives of celiac patients, the discordances detected in this study showed that the use of only one method can lead to false negative results. Consequently these relatives will not be submitted to intestinal biopsy to confirm the diagnosis of celiac disease, and to the correct and earlier treatment.

Serological and Clinical Follow-Up of Relatives of Celiac Disease Patients from Southern Brazil

Background/Aims: In this study, a clinical and serological follow-up of 8–10 years was performed in relatives of celiac disease (CD) patients from southern Brazil. The occurrence of new CD cases in the families and the use of two different IgA-tTG enzyme-linked immunosorbent assay (ELISA) kits were also evaluated. Methods: Serum samples of 233 relatives, 186 recruited between 1997 and 2000 (phase I) and 138 between 2006 and 2007 (phase II: 91 of the follow-up group and 47 newly tested), were analyzed. As a comparison group, 100 unrelated healthy individuals were evaluated. IgA-EmA was tested by indirect immunofluorescence and IgA-tTG by ELISA. Results: A significant increase in IgA-EmA/IgA-tTG was detected in relatives of patients with CD when compared to controls (p ≤ 0.001). The positivity of antibodies was higher in females (2.4:1 in phase II; p = 0.039), and its high frequency amongst siblings (∼18.81%) highlights the risk of CD in these individuals. The distribution of antibodies by age suggested that CD can occur at any age in relatives, calling attention to the newly tested relatives >60 years of age (p = 0.0657). A better performance of ELISA kits with human tTG was observed. The confirmation of 13 biopsy-proven new CD cases (5.6%; 13/233) at present points out the predisposition to CD in these individuals and the high specificity of concurrently positive antibodies in relatives, especially when both are present in high titers. Conclusion: These results emphasize the familial risk to develop CD and the value of serological screening as an instrument for identifying this disease.