Uniparental markers reveal new insights on subcontinental ancestry and sex-biased admixture in Brazil.

The Brazilian population is a product of asymmetric admixture among European men and Amerindian and African women. However, Brazilian subcontinental ancestry is scarcely documented, especially regarding its African roots. Here, we aimed to unveil the uniparental continental and subcontinental contributions from distinct Brazilian regions, including South (n = 43), Southeast (n = 71), the poorly genetically characterized Central-Western region (n = 323), and a subset of unique Brazilian Amerindians (n = 24), in the context of their genome-wide ancestral contributions. The overwhelming majority of European Y haplogroups (85%) contrast sharply with the predominant African and Amerindian mtDNA haplogroups (73.2%) in admixed populations, whereas in Amerindians, non-Native haplogroups could only be detected through the paternal line. Our in-depth investigation of uniparental markers showed signals of an Andean and Central-Brazilian Amerindian maternal contribution to Southeastern and Central-Western Brazil (83.1 ± 2.1% and 56.9 ± 0.2%, respectively), the last having the highest paternal Amerindian ancestry yet described for an admixed Brazilian region (9.7%) and contrasting with higher Southern-Brazilian Amerindian contribution to Southern Brazil (59.6 ± 1%). Unlike the higher African Bantu contribution previously reported for the South and Southeast, a relevant Western African non-Bantu contribution was detected in those regions (85.7 ± 5% and 71.8 ± 10.8% respectively). In contrast, a higher Bantu contribution was described for the first time in the Central-West (64.8 ± 1.3% maternal and 86.9 ± 9.6% paternal). We observed sex-biased signatures consistent with the historically recorded Brazilian colonization and added new insights in the subcontinental maternal ancestry of Brazilians from regions never studied at this level.

Genetic variability of immune-related lncRNAs: polymorphisms in LINC-PINT and LY86-AS1 are associated with pemphigus foliaceus susceptibility.

Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central-Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non-coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune-related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune-related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC-PINT and LY86-AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p < .05 without overlapping with protein-coding genes). Among them, the LINC-PINT SNP rs10228040*A (OR = 1.47, p = .012) was also associated with increased susceptibility for sporadic PF (OR = 2.28, p = .002). Moreover, the A+ carriers of LY86-AS1*rs12192707 mark lowest LY86-AS1 RNA levels, which might be associated with a decreasing autoimmune response. Our results suggest a critical role of lncRNA variants in immunopathogenesis of both PF endemic and sporadic forms.

A genetic variant in microRNA-146a is associated with sporadic breast cancer in a Southern Brazilian Population.

MicroRNAs (miRNAs) play an essential role in gene expression and affect the development of tumours, including breast cancer (BC). Polymorphisms in miRNA genes can affect the interaction of miRNAs with their target messenger RNA by interfering, creating or disrupting target sites. The single nucleotide polymorphism (SNP) rs2910164, located in the seed region of miR146a, was shown to be associated with BC among different populations. In the present study, we investigated whether rs2910164 is associated with BC in 326 patients and 411 controls from a Brazilian population of predominantly European ancestry. The presence of the allele rs2910164*C was associated with an increased risk of BC (OR=1.4, 95% CI=1.03-1.85, p = 0.03). We also analysed publicly available RNA-seq data to evaluate if miR146a is differentially expressed in different subtypes of BC. Genotyping was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). By leveraging public data from TCGA database, we analysed 461 patients and found that miR146a is significantly more expressed in BC than in non-tumor tissue (1.47 fold, p = 0.02) and is expressed to a greater degree in aggressive BC subtypes.

Screening the full leucocyte receptor complex genomic region revealed associations with pemphigus that might be explained by gene regulation.

Pemphigus foliaceus (PF) is a blistering autoimmune skin disease rare in most of the world but endemic in certain regions of Brazil. PF is characterized by the detachment of epidermal cells and the presence of autoantibodies against desmoglein 1. In previous studies, we have shown that genetic polymorphisms and variable expression levels of certain leucocyte receptor complex (LRC) genes were associated with PF. However, the role of the LRC on PF susceptibility remained to be investigated. Here, we analysed 527 tag single nucleotide polymorphisms (SNPs) distributed within the 1·5 Mb LRC. After quality control, a total of 176 SNPs were analysed in 229 patients with PF and 194 controls. Three SNPs were associated with differential susceptibility to PF. The intergenic variant rs465169 [odds ratio (OR) = 1·50; P = 0·004] is located in a region that might regulate several immune-related genes, including VSTM1, LILRB1/2, LAIR1/2, LILRA3/4 and LENG8. The rs35336528 (OR = 3·44; P = 0·009) and rs1865097 (OR = 0·57; P = 0·005) SNPs in LENG8 and FCAR genes, respectively, were also associated with PF. Moreover, we found four haplotypes with SNPs within the KIR3DL2/3, LAIR2 and LILRB1 genes associated with PF (P < 0·05), which corroborate previously reported associations. Thus, our results confirm the importance of the LRC for differential susceptibility to PF and reveal new markers that might influence expression levels of several LRC genes, as well as candidates for further functional studies.

Genetic variation in the non-coding genome: Involvement of micro-RNAs and long non-coding RNAs in disease.

It has been found that the majority of disease-associated genetic variants identified by genome-wide association studies are located outside of protein-coding regions, where they seem to affect regions that control transcription (promoters, enhancers) and non-coding RNAs that also can influence gene expression. In this review, we focus on two classes of non-coding RNAs that are currently a major focus of interest: micro-RNAs and long non-coding RNAs. We describe their biogenesis, suggested mechanism of action, and discuss how these non-coding RNAs might be affected by disease-associated genetic alterations. The discovery of these alterations has already contributed to a better understanding of the etiopathology of human diseases and yielded insight into the function of these non-coding RNAs. We also provide an overview of available databases, bioinformatics tools, and high-throughput techniques that can be used to study the mechanism of action of individual non-coding RNAs. This article is part of a Special Issue entitled: From Genome to Function.

Hyper-physiologic mechanical cues, as an osteoarthritis disease-relevant environmental perturbation, cause a critical shift in set points of methylation at transcriptionally active CpG sites in neo-cartilage organoids.

BACKGROUND: Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stiffness, pain, and a significant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (Guilak in Best Pract Res Clin Rheumatol 25:815-823, 2011). It has been shown that post-mitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative impact on cellular performance. We hypothesize that hyper-physiologic mechanical loading leads to the accumulation of altered epigenetic markers in articular chondrocytes, resulting in a loss of the tightly regulated balance of gene expression that leads to a dysregulated state characteristic of the OA disease state. RESULTS: We showed that hyper-physiological loading evokes consistent changes in CpGs associated with expression changes (ML-tCpGs) in ITGA5, CAV1, and CD44, among other genes, which together act in pathways such as anatomical structure morphogenesis (GO:0009653) and response to wound healing (GO:0042060). Moreover, by comparing the ML-tCpGs and their associated pathways to tCpGs in OA pathophysiology (OA-tCpGs), we observed a modest but particular interconnected overlap with notable genes such as CD44 and ITGA5. These genes could indeed represent lasting detrimental changes to the phenotypic state of chondrocytes due to mechanical perturbations that occurred earlier in life. The latter is further suggested by the association between methylation levels of ML-tCpGs mapped to CD44 and OA severity. CONCLUSION: Our findings confirm that hyper-physiological mechanical cues evoke changes to the methylome-wide landscape of chondrocytes, concomitant with detrimental changes in positional gene expression levels (ML-tCpGs). Since CAV1, ITGA5, and CD44 are subject to such changes and are central and overlapping with OA-tCpGs of primary chondrocytes, we propose that accumulation of hyper-physiological mechanical cues can evoke long-lasting, detrimental changes in set points of gene expression that influence the phenotypic healthy state of chondrocytes. Future studies are necessary to confirm this hypothesis.

Hyper-physiologic mechanical cues, as an osteoarthritis disease relevant environmental perturbation, cause a critical shift in set-points of methylation at transcriptionally active CpG sites in neo-cartilage organoids.

Background: Osteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stiffness, pain, and a significant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (1). It has been shown that post-mitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative impact on cellular performance. We hypothesize that hyper-physiologic mechanical loading leads to the accumulation of altered epigenetic markers in articular chondrocytes, resulting in a loss of the tightly regulated balance of gene expression that leads to a dysregulated state characteristic of the OA disease state. Results: We showed that hyper-physiological loading evokes consistent changes in ML-tCpGs associated with expression changes in ITGA5, CAV1, and CD44, among other genes, which together act in pathways such as anatomical structure morphogenesis (GO:0009653) and response to wound healing (GO:0042060). Moreover, by comparing the ML-tCpGs and their associated pathways to tCpGs in OA pathophysiology, we observed a modest but particular interconnected overlap with notable genes such as CD44 and ITGA5. These genes could indeed represent lasting detrimental changes to the phenotypic state of chondrocytes due to mechanical perturbations that occurred earlier in life. The latter is further suggested by the association between methylation levels of ML-tCpGs mapped to CD44 and OA severity. Conclusion: Our findings confirm that hyper-physiological mechanical cues evoke changes to the methylome-wide landscape of chondrocytes, concomitant with detrimental changes in positional gene expression levels (ML-tCpGs). Since CAV1, ITGA5, and CD44 are subject to such changes and are central and overlapping with OA-tCPGs of primary chondrocytes, we propose that accumulation of hyper-physiological mechanical cues can evoke long-lasting, detrimental changes in set points of gene expression that influence the phenotypic healthy state of chondrocytes. Future studies are necessary to confirm this hypothesis.

Characterizing the secretome of licensed hiPSC-derived MSCs.

Although mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. RNA sequencing confirmed high resemblance, with average Pearson correlation of 0.88 and Jaccard similarity index of 0.99, and similar to hBMSCs the hiMSCs released extracellular vesicles with in vitro immunomodulatory properties. Potency assay with TNFα and IFNγ demonstrated an increase in well-known immunomodulatory genes such as IDO1, CXCL8/IL8, and HLA-DRA which was also highlighted by enhanced secretion in the media. Notably, expression of 125 genes increased more than 1000-fold. These genes were predicted to be regulated by NFΚB signaling, known to play a central role in immune response. Altogether, our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.

25-hydroxy-vitamin D levels among Callithrix penicillata primate species raised in captivity.

BACKGROUND: Animals in captivity should receive adequate sunlight exposure for sufficient generation of vitamin D [25(OH)D]. In the present study, 25(OH)D serum levels of 84 Callithrix penicillata primates were evaluated. OBJECTIVES: To determine 25(OH)D levels of those animals; to evaluate the influence of gender and period of sunlight exposure on their 25(OH)D levels. METHODS: Three groups were evaluated: group 1 (n = 29) on free sunlight exposure; group 2 (n = 34) on partial sunlight exposure; group 3 (n = 21) without sunlight exposure. RESULTS: The obtained 25(OH)D values were: group 1, 121.2 +/- 33.3 ng/ml; group 2, 115.2 +/- 32.2 ng/ml; group 3, 53.3 +/- 10.4 ng/ml. Significant statistical differences were obtained between groups 1 and 3 (p < 0.001) and groups 2 and 3 (p < 0.001); no statistical difference was found between genders. CONCLUSION: Direct sunlight exposure is essential for 25(OH)D sufficiency and it is proposed that the 25(OH)D normal range for captive Callithrix penicillata would be from 104.8 to 137.1 ng/ml (CI = 95%).

Elucidating Epigenetic Regulation by Identifying Functional cis-Acting Long Noncoding RNAs and Their Targets in Osteoarthritic Articular Cartilage.

OBJECTIVE: To identify robustly differentially expressed long noncoding RNAs (lncRNAs) with osteoarthritis (OA) pathophysiology in cartilage and to explore potential target messenger RNA (mRNA) by establishing coexpression networks, followed by functional validation. METHODS: RNA sequencing was performed on macroscopically lesioned and preserved OA cartilage from patients who underwent joint replacement surgery due to OA (n = 98). Differential expression analysis was performed on lncRNAs that were annotated in GENCODE and Ensembl databases. To identify potential interactions, correlations were calculated between the identified differentially expressed lncRNAs and the previously reported differentially expressed protein-coding genes in the same samples. Modulation of chondrocyte lncRNA expression was achieved using locked nucleic acid GapmeRs. RESULTS: By applying our in-house pipeline, we identified 5,053 lncRNAs that were robustly expressed, of which 191 were significantly differentially expressed (according to false discovery rate) between lesioned and preserved OA cartilage. Upon integrating mRNA sequencing data, we showed that intergenic and antisense differentially expressed lncRNAs demonstrate high, positive correlations with their respective flanking sense genes. To functionally validate this observation, we selected P3H2-AS1, which was down-regulated in primary chondrocytes, resulting in the down-regulation of P3H2 gene expression levels. As such, we can confirm that P3H2-AS1 regulates its sense gene P3H2. CONCLUSION: By applying an improved detection strategy, robustly differentially expressed lncRNAs in OA cartilage were detected. Integration of these lncRNAs with differential mRNA expression levels in the same samples provided insight into their regulatory networks. Our data indicates that intergenic and antisense lncRNAs play an important role in regulating the pathophysiology of OA.

Prevalence of celiac disease among first degree relatives of Brazilian celiac patients.

BACKGROUND: Several studies have shown that celiac disease, an autoimmune disorder that occurs in genetically susceptible individuals, is highly prevalent among relatives of celiac patients. AIM: To determine the prevalence of celiac disease in a group of first degree relatives of Brazilian celiac patients. METHODS: First degree relatives of celiac patients attending the Brasilia University Hospital Pediatric Gastroenterology Outpatient Clinic or the Celiac Disease Investigation Center, Brasília, DF, Brazil, between March 2001 and November 2004 were invited to undergo serological screening for celiac disease applying the IgA anti-endomysium antibody test (IgA-EMA). All positive IgA-EMA sera underwent a second screening using the IgA anti-tissue transglutaminase antibodies test. Duodenal or small intestinal biopsies were performed in all subjects positive to serological testing. Biopsy samples were classified as type (O) normal, (I) infiltrative, (II) infiltrative hyperplastic, (III) flat destructive, and (IV) atrophic hypoplastic. The final diagnosis was ascertained in subjects showing positive serological tests and a grade I to III small intestinal lesion. RESULTS: Nine new cases of celiac disease were found among the 188 first degree relatives tested (4.8%). CONCLUSION: The present study confirms the high prevalence of celiac disease among first degree celiac patients relatives and reinforces the need of extensive diagnostic screening in this specific group.

Besides Pathology: Long Non-Coding RNA in Cell and Tissue Homeostasis.

A significant proportion of mammalian genomes corresponds to genes that transcribe long non-coding RNAs (lncRNAs). Throughout the last decade, the number of studies concerning the roles played by lncRNAs in different biological processes has increased considerably. This intense interest in lncRNAs has produced a major shift in our understanding of gene and genome regulation and structure. It became apparent that lncRNAs regulate gene expression through several mechanisms. These RNAs function as transcriptional or post-transcriptional regulators through binding to histone-modifying complexes, to DNA, to transcription factors and other DNA binding proteins, to RNA polymerase II, to mRNA, or through the modulation of microRNA or enzyme function. Often, the lncRNA transcription itself rather than the lncRNA product appears to be regulatory. In this review, we highlight studies identifying lncRNAs in the homeostasis of various cell and tissue types or demonstrating their effects in the expression of protein-coding or other non-coding RNA genes.

Sparking Fire Under the Skin? Answers From the Association of Complement Genes With Pemphigus Foliaceus.

Skin blisters of pemphigus foliaceus (PF) present concomitant deposition of autoantibodies and components of the complement system (CS), whose gene polymorphisms are associated with susceptibility to different autoimmune diseases. To investigate these in PF, we evaluated 992 single-nucleotide polymorphisms (SNPs) of 44 CS genes, genotyped through microarray hybridization in 229 PF patients and 194 controls. After excluding SNPs with minor allele frequency <1%, out of Hardy-Weinberg equilibrium in controls or in strong linkage disequilibrium (r2 ≥ 0.8), 201 SNPs remained for logistic regression. Polymorphisms of 11 genes were associated with PF. MASP1 encodes a crucial serine protease of the lectin pathway (rs13094773: OR = 0.5, p = 0.0316; rs850309: OR = 0.23, p = 0.03; rs3864098: OR = 1.53, p = 0.0383; rs698104: OR = 1.52, p = 0.0424; rs72549154: OR = 0.55, p = 0.0453). C9 (rs187875: OR = 1.46, p = 0.0189; rs700218: OR = 0.12, p = 0.0471) and C8A (rs11206934: OR = 4.02, p = 0.0323) encode proteins of the membrane attack complex (MAC) and C5AR1 (rs10404456: OR = 1.43, p = 0.0155), a potent anaphylatoxin-receptor. Two encode complement regulators: MAC-blocking CD59 (rs1047581: OR = 0.62, p = 0.0152) and alternative pathway-blocking CFH (rs34388368: OR = 2.57, p = 0.0195). One encodes opsonin: C3 (rs4807895: OR = 2.52, p = 0.0239), whereas four encode receptors for C3 fragments: CR1 (haplotype with rs6656401: OR = 1.37, p = 0.0382), CR2 (rs2182911: OR = 0.23, p = 0.0263), ITGAM (CR3, rs12928810: OR = 0.66, p = 0.0435), and ITGAX (CR4, rs11574637: OR = 0.63, p = 0.0056). Associations reinforced former findings, regarding differential gene expression, serum levels, C3, and MAC deposition on lesions. Deregulation of previously barely noticed processes, e.g., the lectin and alternative pathways and opsonization-mediated phagocytosis, also modulate PF susceptibility. The results open new crucial avenues for understanding disease etiology and may improve PF treatment through additional therapeutic targets.

Autism spectrum disorder and celiac disease: no evidence for a link.

OBJECTIVE: To evaluate the possible association between celiac disease (CD) and/or gluten sensitivity (GS) and autism spectrum disorder (ASD). METHODS: Occurrences of CD were determined in a group of children and adolescents affected by ASD and, conversely, occurrences of ASD were assessed in a group of biopsy-proven celiac patients. To detect the possible existence of GS, the levels of antigliadin antibodies in ASD patients were assessed and compared with the levels in a group of non-celiac children. RESULTS: The prevalence of CD or GS in ASD patients was not greater than in groups originating from the same geographical area. Similarly the prevalence of ASD was not greater than in a group of biopsy-proven CD patients. CONCLUSION: No statistically demonstrable association was found between CD or GS and ASD. Consequently, routine screening for CD or GS in all patients with ASD is, at this moment, neither justified nor cost-effective.

Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease.

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.

Serologic screening and genetic testing among brazilian patients with celiac disease and their first degree relatives.

CONTEXT: Celiac disease susceptibility has been shown to be associated with the HLA alleles DQA1*0501 and DQB1*0201 (together encoding the DQ2 heterodimer) that are present in practically all celiac disease patients. The DQ8 heterodimer (coded by DQA1*03-DQB1*0302), which is carried on a DRB1*04 (DR4) haplotype, is commonly encoded for by the few celiacs who do not carry the DQ2 heterodimer. Only a few celiac disease patients have been reported without these known risk alleles. OBJECTIVE: To assess the prevalence of celiac disease in a group of first degree relatives of celiac patients, and the frequency of HLA predisposing alleles both in the group of celiac patients and in their first degree relatives, identifying those first degree relatives who would need further screening for celiac disease. METHODS: Ninety celiac disease patients and 207 first degree relatives underwent serologic screening for celiac disease (endomysial and transglutaminase antibodies) followed by intestinal biopsy in positive patients. The HLA-DQA1*0501, DQB1*0201 and DRB1*04 frequencies of celiac patients and their first degree relatives were determined utilizing the PCR method. RESULTS: All the celiac disease patients (n = 90) with the exception of one (1.1%) carried at least one of the alleles investigated. Altogether 11 (5.3%) of the investigated first degree relatives did not carry any of the alleles studied. Fourteen (6.7%) new cases of celiac disease were found among the 207 celiac disease patients first degree relatives. CONCLUSIONS: Considering the cost-benefit of the HLA typing of all the first degree relatives of celiac patients, their HLA status should be decided on an individual basis, taking account of their profile and preferences, and the existence of other medical conditions.

Serological screening for celiac disease in symptomatic 12 to 36 month-old children.

CONTEXT: The correct diagnosis of celiac disease in environmentally deprived children is frequently hindered by the common presence of other causes for the classical celiac disease symptoms: malnutrition, failure to thrive and frequent diarrheas. OBJECTIVES: To determine the prevalence of celiac disease in a group of 12 to 36 month-old children using immunoglobulin antibodies against gliadin (IgG and IgA-AGA), against endomysium (IgA-EMA), and against human tissue transglutaminase (IgA-tTG) as screening method. METHODS: A total of 214 children (114 boys), aged 12 to 36 months, on gluten-containing diet, were admitted to the study. IgG and IgA-AGA, IgA-tTG and IgA-EMA tests were performed in all sera. Biopsy was obtained from all children showing positive result in one or more of the serologic tests, excluding those in which IgG-AGA had been the only positive result. In those cases, polymerase chain reaction (PCR) HLA genotyping for the identification of celiac disease predisposing alleles was applied. HLA genotyping was also performed to confirm the diagnosis in children identified as celiac by means of positive serologic testing and compatible biopsy results. RESULTS: Normal results were obtained in 131 children. Ten children out of 68 identified as positive exclusively on the IgG-AGA test disclosed the presence of celiac disease predisposing alleles on PCR and underwent jejunal biopsy with normal results. All serologic tests were positive in four children. A fifth child showed positive IgG and IgA-AGA and IgA-tTG results but disclosed a negative IgA-EMA test. Jejunal biopsy of these five children revealed characteristic lesions of celiac disease. CONCLUSION: A prevalence of 2.3% was found among symptomatic 12- to 36-month-old children that had not been previously diagnosed as celiac.

Screening for celiac disease among patients with Turner syndrome in Brasília, DF, midwest region of Brazil.

CONTEXT: Several studies have demonstrated a higher prevalence of celiac disease (CD) among females with Turner syndrome when compared to the general population. Nevertheless, there is no record in literature concerning this investigation among Brazilian patients. OBJECTIVE: To assess the prevalence of CD among a group of Brazilian patients with Turner syndrome. METHODS: Fifty-six females with Turner syndrome and on gluten-containing diet were screened for CD utilizing immunoglobulin A antiendomysium (IgA-EMA) and immunoglobulin A anti-tissue transglutaminase (IgA-tTG) antibody assays. Additionally, they were genotyped for CD human leukocyte antigen (CD-HLA) predisposing alleles. Patients showing positivity in serological testing were offered to perform small intestine biopsy for histological confirmation. RESULTS: Mean age at diagnosis of Turner syndrome was 5.5 ± 4.4 years; mean age at screening for CD was 17.0 ± 9.3 years (from 10 months of age to 52 years). Two girls were positive for IgA-EMA and IgA-tTG, presented predisposing HLA-DQ2 alleles and both had the diagnosis of CD confirmed by jejunal biopsy. CONCLUSION: The 3.6% prevalence of biopsy-proven CD among this group of females with Turner syndrome is 10 times higher than the one among females from the general population of the same geographical area. This result provides additional support to an association between these two disorders and restates that girls and women with Turner syndrome represent a high risk population for developing CD.

Maternal celiac disease: improbable risk factor for neural tube defect.

OBJECTIVES: To verify the existence of possible relation between maternal celiac disease (CD) and the appearance of neural tube defects (NTD) in the newborn serological testing in 208 mothers with NTD-affected pregnancy were performed. METHODS: All sera were tested for total serum immunoglobulin A (IgA) levels and for IgA class endomysial antibody using indirect immunofluorescence technique. Participant age ranged from 19 to 43 years (mean: 33 years). None had been previously investigated for or had a family history of CD. RESULTS: Immunoglobulin levels were normal and results of the IgA-endomysial antibody tests were negative in all women tested. CONCLUSION: This study, although nonconclusive, did not corroborate earlier findings described in the literature of increased frequency of CD in mothers with a history of NTD-affected pregnancy. At this moment we feel that a routine screening for CD in pregnant women to avoid a possible pregnancy aggravated by NTD would not be justifiable.

Autism spectrum disorder and celiac disease: no evidence for a link / Transtorno autístico e doença celíaca: sem evidências de associação

OBJECTIVE: To evaluate the possible association between celiac disease (CD) and/or gluten sensitivity (GS) and autism spectrum disorder (ASD). METHODS: Occurrences of CD were determined in a group of children and adolescents affected by ASD and, conversely, occurrences of ASD were assessed in a group of biopsy-proven celiac patients. To detect the possible existence of GS, the levels of antigliadin antibodies in ASD patients were assessed and compared with the levels in a group of non-celiac children. RESULTS: The prevalence of CD or GS in ASD patients was not greater than in groups originating from the same geographical area. Similarly the prevalence of ASD was not greater than in a group of biopsy-proven CD patients. CONCLUSION: No statistically demonstrable association was found between CD or GS and ASD. Consequently, routine screening for CD or GS in all patients with ASD is, at this moment, neither justified nor cost-effective.

OBJETIVO: Avaliar a possível associação entre doença celíaca (DC) e/ou sensibilidade ao glúten (SG) e transtorno do espectro autista (TEA). MÉTODOS: Ocorrências de DC foram determinadas em um grupo de crianças e adolescentes afetados pelo TEA e a ocorrência d TEA foi avaliada em um grupo de pacientes com DC comprovada por biópsia. Para detectar a possível existência de SG, foram determinados níveis de anticorpos antigliadina em pacientes com TEA e comparados ao grupo de crianças sem a doença celíaca. RESULTADOS: A prevalência de DC ou SG não foi maior no grupo de pacientes com TEA quando comparada a grupos de indivíduos originários da mesma região geográfica. De modo similar, a prevalência do TEA não foi maior ao ser comparada ao grupo de pacientes com DC. CONCLUSÃO: Não houve associação estatisticamente demonstrável entre DC ou SG e TEA. Consequentemente, não são justificáveis, no momento, exames de rotina para detecção de DC ou SG em pacientes com TEA.