Prevalence of Celiac Disease in Indian Children with Down Syndrome and its Clinical and Laboratory Predictors

Objective

To study the prevalence of celiac disease in Indian children with Down syndrome and evaluate its clinical and laboratory predictors.

Methods

Prevalence of celiac disease (CD) was assessed in 100 patients with Down syndrome (DS) attending pediatric genetic clinic at All India Institute of Medical Sciences,in a prospective observational study, based on the characteristic symptomatology, positive indirect immunofluorescence anti endomyseal antibody(anti EMA) test and duodenal histology based on adapted Marsh criteria. Clinical and laboratory features were compared in children having both CD and DS and those with DS alone.

Results

Anti EMA was positive in 7 out of 100 patients screened for CD; 6 in whom the duodenal biopsy could be done showed histopathological features consistent with celiac disease. Amongst various clinical features evaluated as possible risk factors; pallor reached statistical significance (OR?=?7.04 95%CI 1.08–45.7). In addition anemia (Hb <11 g%) was significantly associated with CD (p?=?0.06).

Conclusions

The present results showed a high prevalence of CD in DS children in a tertiary hospital in India and low hemoglobin to be an important risk factor. The authors recommend that all Indian children with Down syndrome, particularly those with anemia should be screened for celiac disease.     

The prevalence of celiac disease in at-risk groups of children in the United States

OBJECTIVE: In contrast to its prevalence in Europe, celiac disease (CD) is considered rare in the United States. We aimed to determine the prevalence of CD in children presenting with symptoms or conditions associated with CD. STUDY DESIGN: Individuals aged 6 months to 20 years were screened for IgG and IgA antigliadin (AGA-IgG and AGA-IgA) and antiendomysium (EMA) antibodies. Those with only elevated AGA-IgG were screened for selective IgA deficiency. Patients with elevated EMA, or AGA-IgG elevation and selective IgA deficiency, were advised to undergo small intestinal biopsy. RESULTS: A total of 1200 individuals were studied; 34 were EMA positive-26 (19 EMA positive) consented to biopsy and 21 had CD, giving a prevalence of 1 in 57 (21/1200). Including the 15 EMA positive patients who refused a biopsy, the prevalence of CD in this study could be as high as 1 in 33 (36/1200). CONCLUSIONS: CD is not rare in the United States and may be as common as in Europe. AGA and EMA are useful for identifying patients who should undergo a small intestinal biopsy.     

IgA endomysium antibodies--an early predictor for celiac disease in children without villous atrophy.

AIM: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD). METHODS: Children with suspected CD and positive EMA (>or=1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n=133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n=39; 59% female, mean age at the first biopsy 7.3 years, range 1.4-16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n=94; 56% female; mean age 7.6 years at the first biopsy, range 0.70-17). RESULTS: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2-7 years (median 4.5 years). CONCLUSIONS: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.     

IgA endomysium antibodies – an early predictor for celiac disease in children without villous atrophy

Aim: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD).
Methods: Children with suspected CD and positive EMA (≥1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n = 133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n = 39; 59% female, mean age at the first biopsy 7.3 years, range 1.4–16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n = 94; 56% female; mean age 7.6 years at the first biopsy, range 0.70–17).
Results: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2–7 years (median 4.5 years).
Conclusions: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.     

Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium antibodies

The usefulness of antigliadin (AGA) and antiendomysium antibodies (EMA) as a screening test for coeliac disease (CD) in 113 Down syndrome (DS) patients (61 children) was evaluated. AGA IgA were present in 22.1%, AGA IgG in 48.6%, EMA in 6.2%. Four symptomatic patients, AGA- and EMA-positive, were affected by CD (3.5%). In three AGA- and EMA-positive subjects, permission for intestinal biopsy was refused, while in two AGA-positive and EMA-negative children, the intestinal mucosa was normal. Our study confirms the association of CD and DS, and suggests the usefulness of EMA determination as a test for selecting DS patients for intestinal biopsy.     

Celiac disease in children with Down syndrome: Importance of follow-up and serologic screening

BACKGROUND: Celiac disease, also known as gluten-sensitive enteropathy, is a chronic inflammation disease of the small intestinal mucosa. Detection of Ig-A antigliadin antibodies (AGA) and antiendomysial antibodies (EMA) in serum is important in the diagnosis and screening for celiac disease. Antiendomysial antibodies have greater sensitivity compared to antigliadin antibodies. It has been reported that the prevalence of celiac disease is higher in children with Down syndrome than the other autoimmune conditions. The aim of the present study was to investigate the incidence of celiac disease in children with Down syndrome, to assess the availability of Ig-A AGA and EMA for serologic screening, and to highlight the importance of follow-up for children with Down syndrome. METHODS: Forty-seven children with Down syndrome without known celiac disease were tested for total blood count, thyroid function tests, immunoglobulin values, Ig-A AGA and EMA. Duodenal biopsy was performed on eight patients who showed at least one serologically positive marker. RESULTS: The ages of the children with Down syndrome ranged from 2 to 18 years (30 boys/17 girls). The mean age was 6.55 +/- 3.88. Total blood count and immunoglobulin values were normal. Eleven of the 47 patients (23.40%) were found to be serologically positive, 10 (21.28%) having antigliadin antibody concentrations above normal; and six (12.77%) being positive for antiendomysial antibody. In five patients (10.64%), both Ig-A AGA and EMA concentrations were high and positive. Duodenal biopsies of three of eight cases (37.50%) revealed villous atrophy, lymphocyte infiltration and crypt hyperplasia. Three cases with abnormal biopsy results (100%) were below the 10th percentile for weight and height. Hypo-thyroidism was detected in one of 11 cases where at least one serologic marker was positive. CONCLUSION: Children with Down syndrome should be carefully examined in their follow up, and celiac disease should be considered in cases with growth retardation. Ig-A antigliadin antibodies and EMA are non-invasive, cheap and readily available serologic screening tests for celiac disease, and the positivity of both markers gives the most reliable result.     

Serologic and genetic markers of celiac disease: a sequential study in the screening of first degree relatives

OBJECTIVES: The prevalence of celiac disease (CD) among the relatives and the complications of an undiagnosed CD prompted us to identify a useful disease screening strategy. METHODS: We studied 441 first degree relatives of 208 CD patients by immunoglobulin (Ig)A antiendomysium antibodies (EMA) and radioimmunoprecipitation assay (RIA) IgA antitransglutaminase autoantibodies (TGAA). Of these, 364 were typed for human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes by the polymerase chain reaction sequence specific primers method. It was suggested to the autoantibody-positive subjects that they should undergo intestinal biopsy. RESULTS: TGAA were positive in 46 of 439 relatives, EMA in 38; intestinal lesions related to CD were present in 40 subjects. We also found two immunodeficient fathers with duodenal villous atrophy. In three serology-positive subjects, permission for intestinal biopsy was refused; for another three serology-positive cases, duodenal mucosa was normal. Thus, the strict CD prevalence resulted 9.5%, the enlarged prevalence 10.9%. The DQ2/DQ8 heterodimers were carried in 231 of 364 subjects and in 38 of 40 biopsy-proven celiac patients. Three DQ2-positive parents became positive to the serology during a long-lasting follow-up. CONCLUSIONS: On the basis of a carefully conducted study, CD prevalence in our series was seen as very high. These data suggest an accurate algorithm to select candidates for intestinal biopsy among CD high-risk subjects. First, an evaluation of the sensitive RIA TGAA and of total IgA (in IgA deficiency RIA IgG anti-tissue transglutaminase assay) should be performed. Then, an evaluation of the TGAA and the genetic study would be advisable 2 to 3 years later in negative subjects. Those carrying the DQ2/DQ8 heterodimers should continue the serologic follow-up; the others need a clinical follow-up.     

Prediction of silent celiac disease at diagnosis of childhood type 1 diabetes by tissue transglutaminase autoantibodies and HLA

Abstract: Aims: The aims were to estimate the diagnostic sensitivity and specificity of autoantibodies to tissue transglutaminase (IgA‐ and IgG‐tTG), gliadin (AGA) and endomysium (EMA) in relation to human leukocyte antigen (HLA)‐DQB1 alleles to identify silent celiac disease at diagnosis of type 1 diabetes. Methods: IgA‐ and IgG‐tTG were measured in radioligand binding assays in 165 type 1 diabetic patients. Data on HLA‐DQB1 were available for 148 patients and on both AGA and EMA for 164 patients. For patients considered positive for AGA or EMA, or both, an intestinal biopsy was suggested. HLA‐DQB1 typing was carried out by polymerase chain reaction and hybridization with allele specific probes. Results: Three patients, left out from further study of antibodies, but not from HLA‐DQB1 analysis, had treated celiac disease at diagnosis. Out of the other 162 type 1 diabetic patients tested, nine had IgA‐tTG, six IgG‐tTG, eight EMA, and 11 AGA. Biopsy was suggested for nine patients, of whom six showed villous atrophy, one did not and two refused to participate. Thus, silent celiac disease was probable in 8/162 and biopsy‐verified in 6/162, where five patients were AGA‐positive and six either EMA‐, IgA‐tTG‐ or IgG‐tTG‐positive. Of the 11 patients with celiac disease (three with treated and eight with silent celiac disease), 10 were HLA‐DQB1‐typed, of whom 65% (13/20) had the DQB1*02 allele, compared with 36% (100/276; p = 0.011) of those without celiac disease. IgA‐tTG levels were higher in patients having either *02 or *0302 (0.6; ?1.3–112.4 RU) compared with those not having these alleles (0.4; ?0.7–3.4 RU; p = 0.023). Conclusion: IgA‐tTG are HLA‐DQB1*02‐associated autoantibodies with high sensitivity and specificity for silent celiac disease at diagnosis of type 1 diabetes.     

Antiendomysial antibody detection in biopsy culture allows avoidance of gluten challenge in celiac children

OBJECTIVE: Antiendomysial antibody (EMA) production has been induced in vitro by the small bowel mucosa of celiac disease (CD) patients in clinical remission cultured in the presence of gliadin peptides. The aim of the present study was to use this in vitro system to determine whether it could be used to predict the clinical or histologic relapse to gluten challenge in CD children on a gluten-free diet (GFD). METHODS: Enrolled were 32 CD children and adolescents on GFD (group 1), and 80 controls (group 2) who underwent in vitro gliadin challenge. Subsequently, 24 group 1 CD children underwent in vivo gluten challenge to confirm the diagnosis. Biopsy cultures, with and without gliadin, morphometric analysis, immunoglobulin (Ig)A and IgG1 EMA detection, both in sera and culture supernatants, were performed. RESULTS: Of the 32 group 1 CD patients, 23 were IgA EMA positive in culture supernatants. The other nine were IgG1 EMA positive. All 24 children who had in vivo gluten challenge showed clinical or histologic relapse. All culture supernatants from disease controls belonging to group 2 were both IgA and IgG1 EMA negative, irrespective of gliadin challenge. CONCLUSIONS: Organ culture with in vitro gliadin challenge is able to reproduce the results of in vivo challenge. This system could reduce the need for gluten challenge in celiac children.     

Prevalence of celiac disease and follow-up of EMA in children and adolescents with type 1 diabetes mellitus

BACKGROUND: The prevalence of celiac disease (CD) in children with diabetes mellitus type 1 (DM) is significantly higher than in the nondiabetic population. Most patients with DM and associated CD do not experience typical gastrointestinal symptoms of CD. There is no agreement on the necessity of screening and management of silent CD for patients with DM or on the time scale for screening. Only few data on follow-up evaluation of children with DM and CD-related antibodies are available. METHODS: One hundred fifty-seven patients with DM (mean age, 14.8 years; range, 4-21 years; male, 83) were screened with endomysial antibodies (EMA) between 1993 and 2001. A follow-up period of at least 3 years, with at least 2 EMA measurements, was possible. Group 1 comprised 37 patients whose first measurement was at the onset of DM. Group 2 comprised 120 patients whose first measurement was during the course of the disease. In patients with positive EMA, small bowel biopsy was performed. Thyroid peroxidase (TPO), thyroglobulin (TgA), glutamate decarboxylase (GAD), antiinsulin (IAA), and islet cell antibodies (IA2) were measured in all patients. RESULTS: EMA was positive in 16 patients, in 5 at onset of DM and in 11 during the course of DM (mean duration, 33.6 months; range, 11-105 months). Biopsy results showed normal mucosa in seven patients, increased intraepithelial lymphocyte counts in one, and flat mucosa in eight. There was no significant difference between EMA-positive and EMA-negative patients regarding height, weight, HbA1c level, frequency of hypoglycemia or hyperglycemia, TPO, TgA, GAD, IAA, or IA2. CONCLUSION: This study emphasizes the high prevalence of CD in patients with DM. Although several patients already had positive EMA titers at the onset of DM, seroconversion may also occur during the course of the disease. Screening for CD with EMA or tissue transglutaminase should be included in the initial investigation of DM, but should also be repeated over time to detect late seroconversion.     

Accuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome

OBJECTIVES: To investigate the best approach to screen for celiac disease (CD) in patients with Down syndrome (DS). STUDY DESIGN: One hundred thirty-seven children with DS were followed up longitudinally. CD screening was offered in 1994, 1996, and 1999 by determination of serum immunoglobulin A-anti-endomysium antibodies (AEA). The HLA-DQA1*0501/DQB1*02 allelic combination known to be strongly positively associated with CD was typed. All IgA-AEA-positive children were given the opportunity to undergo a small bowel biopsy: if villous atrophy was found, the diagnosis of CD was established. RESULTS: CD was diagnosed in 11 (8%) children: 8 in 1994 and 3 in 1996. All of them carried the HLA-DQ alleles associated with CD. The presence of symptoms was not useful in discriminating which children could have CD. CONCLUSIONS: Screening once in a lifetime is not enough to detect CD in patients with DS. We propose a new, accurate, and cost-sparing 2-step strategy for screening, based on selection of the individuals with potential CD by HLA-DQ typing and on longitudinal serologic CD screening in this selected group.     

The risk of celiac disease in 107 families with at least two affected siblings

OBJECTIVES: Screening for celiac disease (CD) in the apparently healthy members of 107 nuclear families with two affected siblings (sib pair) and estimating the risk of CD in siblings and parents. METHODS: One hundred seven families from Sweden and southern Norway with at least two affected children were investigated. Frozen sera from 187 of the 192 healthy parents and from 94 of 95 siblings without diagnosed CD were examined for total immunoglobulin A (IgA) and anti-endomysial antibodies (EMA). Individuals with positive antibody titers underwent small intestinal biopsy. RESULTS: Positive test for EMA was found in 6 of 94 (6.3%) siblings without previously diagnosed CD and in 8 of 189 (4.2%) parents. CD was confirmed by small intestinal biopsy in all siblings and seven parents. The estimated risk for CD in multiply affected families was 26.3% for siblings and 12.9% for parents. An unexpected male preponderance was found among the new CD cases (10 males, 3 females). CONCLUSION: The risk of CD in the members of nuclear families with two affected children is approximately three times higher than that when only one child is affected. The high male preponderance of new cases is unexpected and could not be explained fully by more silent disease in males as compared with females. Considering the high level of knowledge about CD in these families, the number of undiagnosed cases is surprisingly high. The authors suggest that serologic screening should be offered to all first-degree relatives of patients with CD.     

Antibodies to gliadin, endomysium, and tissue transglutaminase for the diagnosis of celiac disease.

BACKGROUND: Tissue transglutaminase has recently been identified as the main autoantigen recognized by antiendomysial antibodies in celiac disease. Serum immunoglobulin (Ig)A antibodies to tissue transglutaminase (tTG-ab) determined by an enzyme-linked immunosorbent assay (ELISA) technique have been reported to correlate closely with IgA antiendomysial antibodies (EMA). The purpose of this study was to assess the sensitivity, specificity, and predictive value of tTG-ab measured by a commercially available ELISA technique, compared with those of EMA and IgA antigliadin antibodies (AGA) for the diagnosis of celiac disease. METHODS: Twenty-seven serum samples were obtained from patients with untreated celiac disease, 37 from patients who had had gluten withdrawn from their diets for varying time spans, and 34 from control subjects without celiac disease. All were younger than 14 years. Presence of tTG-ab and AGA was determined by ELISA and of EMA by indirect immunofluorescence. RESULTS: Twenty-six of 27 serum samples obtained from patients at the time of diagnosis of celiac disease were AGA positive. All 27 (concordance rate 100%) were positive for EMA and tTG-ab. Of the 34 control subjects, 1 was for AGA and 2 for tTG-ab. All 34 were negative for EMA. Sensitivity, specificity, positive predictive value, and negative predictive value within this group were, for tTG-ab: 100%, 94%, 93%, and 100%, respectively; for EMA: all four indexes were 100%; and for AGA: 96%, 97%, 96%, and 97%, respectively. Of the 37 with treated celiac disease, 2 were AGA positive, 9 were EMA positive, and 6 were tTG-ab positive. The concordance rate between EMA and tTG-ab was 100% in the group with untreated celiac disease, 94% in the control subjects, and 76% in the group with treated celiac disease. CONCLUSIONS: Immunoglobulin A antibodies to tissue transglutaminase are new, highly sensitive, and specific markers of celiac disease. They can be determined easily by an accurate, comparatively cheap technique and thereby may advantageously replace the EMA marker traditionally used.     

Antiendomysial antibody test reliability in children with frequent diarrhea and malnutrition: is it celiac disease?

BACKGROUND: The aim of this study was to evaluate the specificity of the immunoglobulin A (IgA) antiendomysial antibody test in the diagnosis of celiac disease in a group of malnourished children with acute diarrhea, chronic diarrhea, or parasitosis, because the reliability of this test has been questioned when applied to this specific group of patients. METHODS: Serum IgA level, IgA antiendomysial antibody (EMA) test, and stool examination were performed in 315 children, ranging in age 6 months to 13 years (range, 41 +/- 2.9 months), affected by malnutrition, isolated or in association with diarrhea or parasitosis. Independent of results, 33 children with a strong suspicion of celiac disease, also underwent IgA antitransglutaminase antibody test and jejunal biopsy. RESULTS: The EMA test was negative in 313 children, including the 43 with parasitosis, being positive in two patients in whom biopsy disclosed typical celiac mucosal abnormalities (1:157). The 31 children with negative EMA test who underwent biopsy also showed negative antitransglutaminase antibody results. Their biopsies disclosed normal mucosa in 1 patient, variable degree of jejunal atrophy (grade 1 and 2) in 27 patients, and grade 3 abnormalities in 3 patients. One of these three children, showing severe jejunal atrophy, died. The diagnosis of celiac disease was apparently not confirmed by a protracted gluten challenge in the other two children. CONCLUSIONS: The specificity of the EMA test seems to be high also in children with chronic malnutrition and diarrhea. However, the possibility of false-negative tests among immunologically compromised children cannot be excluded. In doubtful cases, the gluten challenge is required in malnourished children with clinical picture, biopsy finding, and evolution suggestive of celiac disease.     

Screening by anti-endomysium antibody for celiac disease in diabetic children and adolescents in Austria

BACKGROUND: Unrecognized celiac disease (CD) may be found in a substantial proportion of patients with type I diabetes mellitus. METHODS: A cohort of 403 Austrian children and adolescents with type I diabetes mellitus (210 males and 193 females; age range, 1-22 years) was screened for celiac disease using the IgA anti-endomysium antibody test (EMA) and the immunoglobulin (Ig)G anti-gliadin (AGA-IgG) and IgA anti-gliadin (AGA-IgA) antibody test. RESULTS: Twelve patients' sera (2.98%) yielded positive EMA results and two patients' sera (0.49%) with IgA deficiency had high AGA-IgG values. All but one of these patients underwent intestinal biopsy. Six (1.49%) had clear histologic evidence of CD (flat mucosa), whereas three (0.74%) showed minor histologic changes (increase in intraepithelial lymphocytes) and four (0.99%), including the EMA-negative patients with IgA deficiency, had a normal mucosa. When the cases with silent and potential CD were combined, the overall prevalence in the current cohort was 2.98%. There was no difference in the hemoglobin (Hb)A1c level between antibody-positive and -negative patients, and subsequent gluten-free diet did not change this metabolic parameter. CONCLUSION: The prevalence of clinically unrecognized CD, found by EMA screening, is much higher in Austrian children with diabetes than in a comparable population without diabetes. The prevalence of CD in diabetic children in Austria is distinctly lower, however, than in several other countries.     

Symptom positivity is essential for omitting biopsy in children with suspected celiac disease according to the new ESPGHAN guidelines

The aim of this study was to assess the accuracy of serological tests in combination with clinical symptoms for diagnosing celiac disease (CD) according to the new proposed European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. We retrospectively assessed children and adolescents aged 16 months –19 years who were examined for suspicion of CD (n?=?345). Evaluation of clinical symptoms and the presence of tissue transglutaminase (anti-TG-IgA) and endomysial antibodies (EMA-IgA) as well as intestinal biopsies was performed in all patients. Human leukocyte antigens (HLAs) were not included. Among 345 biopsied children, 213 (62 %) children had anti-TG titers >10 times the upper limit of normal (ULN) and positive EMA antibodies. Ninety-nine (29 %) children also had symptoms suggestive of CD in addition to EMA positivity and elevated titers of anti-TG >10 times the ULN. In patients who were asymptomatic, but positive for EMA, and had anti-TG antibodies >10 times the ULN, the specificity of tests for Marsh 2–3 was only 85 %, while in symptomatic patients with the same antibodies levels, the specificity was 99 %. Conclusion: Our results reveal that intestinal biopsies could be omitted in 28 % of patients when the new ESPGHAN guidelines are applied. Due to high accuracy of serological tests in combination with clinical symptoms for diagnosis of CD, the new guideline seems to be applicable even without the use of HLA testing.     

Celiac disease screening in 100 Turkish children with Down syndrome

The aim of this study was to screen a group of children with Down syndrome (DS) for celiac disease, and to define future strategies for screening the patients followed at our center. One hundred children over the age of two years with Down syndrome were serologically screened using antiendomysium antibody (EMA) IgA and serum IgA in order to exclude a concomitant IgA deficiency. Clinical assessment included detailed physical examination, measurement of weight and height plotted on growth charts for DS children followed by an interview of the patients and parents about gastrointestinal symptoms. Only one patient out of 100 (1%) was detected to be EMA IgA-positive. The child's family refused consent for the biopsy procedure. None of the patients had IgA deficiency. Abdominal distention was present in 13 (13%) patients, and anorexia in 9 (9%), vomiting in 7 (7%) and alopecia areata in 2 (2%) patients were also noted. Despite the small number of patients in our group, this result yielding 1% EMA-positivity is the lowest yet determined among DS patients. It has led us to discuss whether or not a change in our screening strategy is necessary.     

Increased prevalence of autoimmune diseases in first-degree relatives of patients with celiac disease

BACKGROUND: The prevalence of autoimmune disorders is increased in patients with celiac disease (CD), and it is unknown whether their first-degree relatives also have a high risk of autoimmune disorders. METHODS: To assess the prevalence of autoimmune diseases in first-degree relatives of CD patients, the authors looked for autoimmune disorders in 225 first-degree relatives of 66 children with CD (group A) and in 232 first-degree relatives of 68 healthy children (group B). For both groups, serologic screening for CD was performed through antiendomysium (EMA) and tissue transglutaminase autoantibodies (tTGAA). EMA- and tTGAA-positive subjects were offered an intestinal biopsy. The age at onset of autoimmune diseases was also recorded in group A. RESULTS: The prevalence of autoimmune disorders was significantly (P = 0.028) higher in group A (11 of 225, 4.8%) than in group B (2 of 232, 0.86%). In relatives of CD patients, the prevalence increased with age (chi2 for trend, 43.5; P < 0.0001). Serologic screening for CD was only positive in group A (15 of 225 subjects). An intestinal biopsy was performed in 13 of these 15 relatives (2 refused biopsy). Eleven of 13 had flat mucosa, with subclinical or silent forms of CD. The prevalence of autoimmune diseases in the EMA- and tTGAA-positive relatives of CD patients was significantly higher (3 of 15, 20%; P = 0.028; odds ratio, 6.3; 95% CI, 1/0.21-1/0.11, 4.9-7.6) than in those who were EMA and tTGAA negative (8/210, 3.8%). CONCLUSIONS: The first-degree relatives of CD patients have an increased risk of autoimmune diseases, most likely connected with unrecognized subclinical or silent forms of CD.     

Celiac disease in a Chilean population carrying Amerindian traits

BACKGROUND: Although clinical manifestations of celiac disease may change throughout life, clinical, histologic, immunologic, and genetic studies show that there are incomplete forms of this condition, making it difficult to define the disease at a given moment. Because there is no information published in the Latin American-Amerindian population, this study was conducted to assess relations between these parameters in Chileans with celiac disease and their first-degree relatives. METHODS: Sixty-two persons with confirmed celiac disease (mean age, 17.9 +/- 5.1 years; 78.3% females) and 126 relatives (mean age, 27.9 +/- 17.2 years; 65.1% females) were evaluated. Clinical manifestations, antiendomysial antibodies (EMAs), and human leukocyte antigen (HLA) haplotypes were studied in patients. Additionally, jejunal biopsy specimens were assessed (light microscopy) in EMA-positive (EMA+) relatives. RESULTS: Of the patients, 24.1% adhered to a strict gluten-free diet; 26% were oligosymptomatic, and none were malnourished; 45% were EMA+; 13.8% who ingested gluten were EMA-negative (EMA-); one patient consuming a strict gluten-free diet was EMA+. The DQA1*0501 allele was present in the highest frequency (48%, P < 0.0005), whereas combinations of DQ8 were predominant. Of the relatives, 4.8% were EMA+; they had a significantly higher frequency of diarrhea, weight loss, and anorexia (P < 0.03); and all had abnormal histology in biopsy specimens. CONCLUSIONS: After childhood, celiac disease is oligosymptomatic and is often unrecognized by patients. Disease in 13.8% of patients and in 4.8% relatives appeared as incomplete forms of celiac disease. Predominance of DQ8 HLA haplotypes reflects the genetic Spanish-Mapuche heritage of this population.     

Celiac disease diagnosis in misdiagnosed children

Antiendomysial antibodies (EMA) are today considered the most sensitive and specific serological marker of celiac disease (CD). The aim of the present study was to assess the occurrence of EMA of IgG isotype in EMA IgA negative children with clinical suspicion of malabsorption and their relationship with CD. Serum EMA IgG1 determination was performed on 30 EMA IgA negative children with clinical suspicion of CD. Total serum IgA levels were further investigated. Sixty children with gastroenterological diseases other than CD were used as control disease patients and 63 healthy children were evaluated as the control group. Eighteen out of 30 children in the study showed EMA IgG1 positivity in sera and a villous height/crypt depth ratio <3:1 as index of intestinal atrophy. It is noticeable that a selective IgA deficiency was present in only 9 of 18 EMA IgG1 positive children. In addition, clinical symptoms, EMA IgG1, and mucosal atrophy disappeared after 8-10 mo on a gluten-free diet. Neither EMA IgA nor EMA IgG1 were detected in the children in the control groups. The other 12 children in study group showed no histologic abnormalities and were EMA IgG1 negative. In this study, we reveal a group of EMA IgG1 CD children without IgA deficiency. The diagnosis was based on the presence of gluten-dependent typical serological and histologic features of CD. Our data suggest that EMA IgG1 determination could be a new tool in the diagnostic workup of CD, useful in avoiding possible misdiagnosis.