Jacqueline Araújo

Prevalence of autoimmune thyroid disease and thyroid dysfunction in young Brazilian patients with type 1 diabetes.

Abstract:  Patients with an autoimmune condition are known to be at higher risk of developing other autoimmune disorders. Type 1 diabetes may be associated with additional autoimmune disorders including autoimmune thyroid disease. The aim of this study was to investigate the prevalence of thyroid autoantibodies in a group of children, adolescents, and young adults with type 1 diabetes from northeastern Brazil as well as their significance for the development of thyroid disorders. The study design was cross‐sectional and descriptive, analyzing young people with a previous type 1 diabetes diagnosis. Two hundred and fourteen children and adolescents with prior diagnosis of type 1 diabetes were evaluated. Antibodies to thyroperoxidase (anti‐TPO) were determined in all patients and thyroid‐stimulating hormone (TSH) levels. The anti‐TPO antibody test was positive in 54 out of the 214 patients studied, resulting in an overall prevalence of 25.2%. Among the anti‐TPO‐positive subjects, females were predominant (72%) over males (28%) (p < 0.001). A total of 55.5% patients with positive anti‐TPO antibodies had abnormal TSH levels. Clinically significant hypothyroidism was found in 29.6% and subclinical hypothyroidism in 22.2% of patients with positive anti‐TPO. Hyperthyroidism was present in only 3% of them. Our results demonstrate the high prevalence of autoimmune thyroiditis in patients with type 1 diabetes and the need for these patients of regular screening to make a precocious diagnosis of thyroid dysfunction.

Serum prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE The association between celiac disease and diabetes mellitus has been known for many decades. This combination can be observed in a large proportion of diabetic patients, who are generally asymptomatic. The objective of this study was to evaluate the seroprevalence of celiac disease in children and adolescents with type 1 diabetes mellitus. METHODS This was a cross-sectional study employing antibody IgA anti-transglutaminase for the serological screening of 354 diabetic children and adolescents treated at pediatric endocrinology clinics in Recife, state of Pernambuco, during the period from January to June 2004. RESULTS The human anti-transglutaminase test was positive in 37/354 patients, resulting in a seroprevalence of 10.5% (95%CI 7.6-14.2%). Male patients predominated (56.8%) over female patients (43.2%) among those that were seropositive, but without statistical significance. Anti-endomysial antibody testing was performed on patients with positive human anti-transglutaminase results, being negative in 14/37 (37.8%) and positive in 22/37 (59.5%). CONCLUSIONS The seroprevalence of celiac disease found in diabetic children and adolescents in Pernambuco is elevated, being comparable with levels observed in studies in North America and Europe and lower than in Africa, suggesting that serological screening for celiac disease should be performed for all children and adolescents with type 1 diabetes mellitus.

Soroprevalência da doença celíaca em crianças e adolescentes com diabetes melito tipo 1

OBJETIVO: A associacao de doenca celiaca e diabetes melito ja e conhecida ha varias decadas. Pode ser encontrada em uma grande proporcao de pacientes diabeticos, que geralmente sao assintomaticos. O objetivo do estudo foi avaliar a soroprevalencia da doenca celiaca em criancas e adolescentes com diabetes melito tipo 1. METODOS: Atraves de um estudo transversal, realizou-se triagem sorologica com anticorpo IgA antitransglutaminase humana em 354 criancas e adolescentes diabeticos, atendidos em ambulatorios de endocrinologia pediatrica de Recife, Pernambuco, no periodo de janeiro a junho de 2004. RESULTADOS: O antitransglutaminase humana foi positivo em 37/354 pacientes, resultando em soroprevalencia de 10,5% (IC95% 7,6-14,2%). Dentre os pacientes soropositivos, houve predominio do sexo masculino (56,8%) em relacao ao feminino (43,2%), porem sem significância estatistica. O anticorpo antiendomisio foi realizado nos pacientes com antitransglutaminase humana positivo, sendo negativo em 14/37 (37,8%) e positivo em 22/37 (59,5%). CONCLUSOES: A soroprevalencia da doenca celiaca em criancas e adolescentes diabeticos encontrada em Pernambuco e elevada, sendo comparavel a observada em estudos da America do Norte e Europa e menor do que na Africa, sugerindo que a triagem sorologica para doenca celiaca seja realizada em todas as criancas e adolescentes com diabetes melito tipo 1.

Interleukin 18 (IL18) gene promoter polymorphisms are associated with type 1 diabetes mellitus in Brazilian patients

Interleukin 18 (IL-18) is a cytokine that plays an important role in the Th1 response, by its ability to induce IFN-γ production in T cells and natural killer cells. Functional variants of IL18 gene has been reported as associated with type 1 diabetes (T1D). In the present study were analyzed three promoter single nucleotide polymorphisms (SNPs), at -656 (rs1946519), -607 (rs1946518) and -137 (rs187238) position, in 181 children and adolescents with T1D and 122 healthy individuals, both from metropolitan area of Recife, Northeast of Brazil. T1D patients were stratified according to the presence autoimmune thyroiditis and celiac disease. Allele and genotype frequencies of IL18 SNPs were Hardy-Weinberg equilibrium in patients and controls. The allele -137G and the haplotype -656G/-607C/-137G were more frequent in T1D patients (OR=1.82 and 1.97, respectively) then in healthy controls. However, those SNPs were not associated with the age of T1D onset as well as with the insurgence of AITD and/or CD in concomitant with T1D patients. Our findings suggest an association between IL18 promoter SNPs and susceptibility to T1D in Brazilian patients.

Vitamin D receptor (VDR) gene polymorphisms and age onset in type 1 diabetes mellitus

Abstract Vitamin D receptor is a mediator of immune responses through the action of vitamin D, which is capable of regulate the insulin secretion by the pancreas. Since polymorphisms in the vitamin D receptor (VDR) gene might modulate vitamin D function, and thus immunologic response, VDR is possibly able to influence the predisposition to type 1 diabetes mellitus (T1DM). The aim of this work was to perform an association study among VDR polymorphisms and T1DM susceptibility, as well as the correlation with the disease onset. Two hundred and four T1DM patients and 217 controls, from Northeast Brazil, were genotyped for five tagSNPs, covering the whole VDR gene. Our results indicated an association between rs1540339 and rs4760648 SNPs (p = 0.02 and p = 0.03, respectively) and T1DM. No association was found with T1DM onset and age at diagnose. To our knowledge, this is the first association study in T1DM where the whole VDR gene was analyzed, and our results indicate that VDR polymorphisms could be important for T1DM susceptibility, but do not seem to be associated to age at disease onset.

Interferon induced with helicase C domain 1 (IFIH1): trends on helicase domain and type 1 diabetes onset.

The Interferon-induced with helicase C domain 1 (IFIH1) gene has been hypothesized as involved in the viral etiology of type 1 diabetes (T1D) and other autoimmune disorders, since it is implicated in viral recognition. In our study we analyzed IFIH1 rs6432714 and rs10930046 SNPs in T1D patients stratified for the presence of celiac disease and autoimmune thyroid disease. No association with susceptibility to develop the diseases was found. The rs6432714, a tag-SNP that represents part of helicase domain of IF1H1 protein showed a trend of association only with T1D development (P>0.025 after Bonferroni adjustment) in log-additive model (OR=1.45, P=0.0365, power=0.99), indicating that helicase domain of IFIH1 protein could be associated with the susceptibility to T1D.

Mannose binding lectin gene polymorphisms and associated auto-immune diseases in type 1 diabetes Brazilian patients

In our study we investigated the possible role of MBL2 functional single nucleotide polymorphisms (SNPs) in the augmented susceptibility to develop other autoimmune diseases in presence of type 1 diabetes (T1D) in a group of Brazilian patients. Patients were stratified for the presence of autoimmune diseases known to be associated with T1D, such as autoimmune thyroid disease (AITD) and celiac disease (CD), and compared with healthy controls (HC). Our findings suggest that MBL2 functional SNPs are more closely related to AITD than to T1D, being MBL2 SNPs frequencies in T1D patients not affected by AITD comparable to the HC ones, while significantly different between AITD patients and patients not affected by the disease. Thus, the association between MBL2 polymorphisms and T1D that we previously reported, seems to result from the stronger association of MBL2 SNPs with another autoimmune disease, the AITD, frequently associated with T1D.

Y chromosome in Turner syndrome: detection of hidden mosaicism and the report of a rare X;Y translocation case

Turner syndrome (TS) is a common genetic disorder in females associated with the absence of complete or parts of a second sex chromosome. In 5-12% of patients, mosaicism for a cell line with a normal or structurally abnormal Y chromosome is identified. The presence of Y-chromosome material is of medical importance because it results in an increased risk of developing gonadal tumours and virilisation. Molecular study and fluorescence in situ hybridisation approaches were used to study 74 Brazilian TS patients in order to determine the frequency of hidden Y-chromosome mosaicism, and to infer the potential risk of developing malignancies. Additionally, we describe one TS girl with a very uncommon karyotype 46,X,der(X)t(X;Y)(p22.3?2;q11.23) comprising a partial monosomy of Xp22.3?2 together with a partial monosomy of Yq11.23. The presence of cryptic Y-chromosome-specific sequences was detected in 2.7% of the cases. All patients with Y-chromosome-positive sequences showed normal female genitalia with no signs of virilisation. Indeed, the clinical data from Y-chromosome-positive patients was very similar to those with Y-negative results. Therefore, we recommend that the search for hidden Y-chromosome mosaicism should be carried out in all TS cases and not be limited to virilised patients or carriers of a specific karyotype.

DC-SIGN polymorphisms are associated to type 1 diabetes mellitus

Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It has been hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immune response by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane protein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory response and T cells activation. Notably, DC-SIGN activation and triggering of the immune response depend on the type of ligand, which may lead to a pro or anti-inflammatory pathway. In our association study, we analysed the SNPs rs4804803 (-336 A>G) and rs735239 (-871 A>G), both at DC-SIGN promoter region, in 210 T1DM patients and 157 healthy controls, also looking for a correlation with the age of onset of the disease. We found that the allele G and genotypes G/G and A/G of SNP-871 (rs735239), as well as the alleles G-G (rs735239-rs4804803) and genotypes combined AA-GG (rs735239-rs4804803) were associated with protection of T1DM development. We did not find association between these variations with the age of onset of the disease and the presence of other autoimmune disorders. Our results suggest that SNPs in DC-SIGN promoter region can be associated to protection for T1DM in the Northeast Brazilian population.

Association between MBL2 polymorphism and T1D: does ethnicity play a role in the susceptibility of this multifactorial disease?

f e o h p The association of functional MBL2 gene polymorphisms ith type 1 diabetes (T1D) is still debated. We demonstrated n a previous work [1] that MBL2 polymorphisms can be conidered potential risk factors for the onset of T1D in a northastern Brazilian population. We screened MBL2 exon 1 unctional polymorphisms in 214 children and adolescents ith T1D and 214 healthy controls matched for age and sex. he carriers of the MBL2 0 allele demonstrated an increased isk of developing T1D [odds ratio 1.72; 95% confidence nterval 1.24 to 2.39]. No correlation between MBL2 polyorphisms and the age of T1D onset existed. Recently, Aittoniemi et al. analyzed MBL2 functional olymorphisms in a larger group of Finnish T1D patients 470) and controls (501) and reported no correlation beween MBL2 polymorphisms and the risk of developing T1D