RESUMO
BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 µg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower (P < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.
Assuntos
Aspergillus niger , Aspergillus , Doença Celíaca , Adulto , Humanos , Doença Celíaca/diagnóstico , Dieta Livre de Glúten , Glutens , Prolil Oligopeptidases , Qualidade de VidaRESUMO
BACKGROUND: Adherence to the gluten-free diet (GFD) is critical to achieving symptom control and mucosal healing in celiac disease (CeD), but its assessment is difficult. OBJECTIVES: We sought to compare stool gluten immunogenic peptides (GIPs) measurements over a 4-wk period with conventional tools commonly used to monitor compliance with a GFD. METHODS: Consecutive adult patients with CeD attending the Small Bowel Section of the Buenos Aires Gastroenterology Hospital were invited to this observational study and were instructed to collect stool samples on Fridays for 4 consecutive weeks. Weekly mean stool GIP concentration was measured was estimated. GIP results were compared with a self-assessment scale of adherence, specific CeD serology, the celiac symptom index, and the assessment by an expert dietitian. RESULTS: Fifty-three CeD patients were enrolled and those with stool GIP ≥0.65 µg/g/wk (n = 13; 24.5%) had higher serum concentrations of IgA deamidated gliadin peptides (DGPs) antibodies [69 (29-109) compared with 14 (13-29); P = 0.0005] and IgA tissue transglutaminase [42 (14-200) compared with 10 (7-16); P = 0.02], higher proportion of cases with IgA DGP antibodies >20 AU/mL (84.6% compared with 33.3%; P = 0.002), and a higher self-estimated adherence score [5 (4-9) compared with 9 (7-10); P = 0.003]. GIP did not correlate with celiac symptom index scores (55.6% compared with 30.8%; P = 0.9). Expert dietitian assessment identified 69% [odds ratio (OR): 5.25; 95% CI: 1.1-27.2; P = 0.01] of nonadherent cases when high stool GIP. Logistic regression analysis determined that IgA DGP (adjusted OR: 1.1; 95% CI: 1.01-1.11; P = 0.02) and males (adjusted OR: 28.3; 95% CI: 1.1-722.6; P = 0.04) were independently associated with excessive gluten exposure. CONCLUSIONS: Weekly stool GIP identifies gluten exposure that is not always detected by commonly used GFD adherence assessment methods. The higher the concentration of stool GIP, the better the predictive value of serology and dietitian interviews. Stool GIP is a useful and practical test for GFD monitoring, particularly for risky gluten exposure in real-life scenarios.
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Doença Celíaca , Glutens , Adulto , Masculino , Humanos , Dieta Livre de Glúten , Estudos Prospectivos , Gliadina , Peptídeos , Cooperação do Paciente , Imunoglobulina ARESUMO
BACKGROUND: Gastroduodenal endoscopy and biopsy following positive specific serology is considered the gold standard to diagnose celiac disease (CeD) in adults. Whether upper endoscopy helps detect comorbid conditions is unknown. AIM: To investigate the prevalence of non-celiac endoscopic findings in patients in whom endoscopy was performed to confirm CeD diagnosis. METHODS: This is an observational, descriptive, multicenter, retrospective study that reports endoscopic findings obtained in adult patients enrolled in local registries from four tertiary centers. We collected data reported on first endoscopy, indicated for investigation of CeD. Diagnosis of CeD was performed by histology (≥ Marsh 2 type mucosal damage) and specific serology. Two European and one North American center included biopsy-confirmed CeD following positive serology. A fourth center (South America) included symptomatic patients undergoing endoscopy, irrespective of CeD serology. The latter cohort included a non-CeD control group. RESULTS: A total of 1328 patients (80% female; 35 years median age) were enrolled, of whom 95.6% had positive specific serology. In 135 patients, endoscopy revealed 163 abnormalities unrelated to CeD (prevalence: 10.1%). Erosive reflux esophagitis (6.4%), gastric erosions (2.0%), and suspicion of esophageal metaplasia (1.2%) were the most common findings. Biopsy-confirmed Barrett's esophagus was infrequent (0.2%). No endoscopic cancer was detected. Older patients (≥ 51 years of age) had a higher prevalence of endoscopic findings than those ≤ 50 (P < 0.01). Within the South American cohort, CeD was associated with a lower rate (8.2%) of comorbid endoscopic findings compared with controls (29.1%; P < 0.001). In the adjusted multivariate analysis of this cohort, having CeD was associated with a 72% reduction in the risk of any endoscopic abnormality (P < 0.0001), and having alarm symptoms was associated with a 37% reduction in the risk of finding at least one endoscopic lesion (P < 0.02). CONCLUSION: In this large multicenter study, young adults with positive CeD serology had few comorbid endoscopic findings. Although patients over 51 years had a high prevalence of non-CeD gastroduodenal mucosal damage, no malignancy or premalignant lesions were found.
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Doença Celíaca , Humanos , Feminino , Masculino , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Estudos Retrospectivos , América do SulRESUMO
BACKGROUND & AIMS: It is not clear how often patients who are on gluten-free diets (GFDs) for treatment of celiac disease still are exposed to gluten. We studied levels of gluten immunogenic peptides (GIP) in fecal and urine samples, collected over 4 weeks, from patients with celiac disease on a long-term GFD. METHODS: We performed a prospective study of 53 adults with celiac disease who had been on a GFD for more than 2 years (median duration, 8 y; interquartile range, 5-12 y) in Argentina. At baseline, symptoms were assessed by the celiac symptom index questionnaire. Patients collected stool each Friday and Saturday and urine samples each Sunday for 4 weeks. We used a commercial enzyme-linked immunosorbent assay to measure GIP in stool and point-of-care tests to measure GIP in urine samples. RESULTS: Overall, 159 of 420 stool and urine samples (37.9%) were positive for GIP; 88.7% of patients had at least 1 fecal or urine sample that was positive for GIP (median, 3 excretions). On weekends (urine samples), 69.8% of patients excreted GIP at least once, compared with 62.3% during weekdays (stool). The number of patients with a sample that was positive for GIP increased over the 4-week study period (urine samples in week 1 vs week 4: P < .05). Patients with symptoms had more weeks in which GIP was detected in stool than patients without symptoms (P < .05). The number of samples that were positive for GIP correlated with titers of deamidated gliadin peptide IgA in patients' blood samples, but not with levels of tissue transglutaminase. CONCLUSIONS: Patients with celiac disease on a long-term GFD still frequently are exposed to gluten. Assays to detect GIP in stool and urine might be used to assist dietitians in assessment of GFD compliance.
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Doença Celíaca , Gliadina , Adulto , Dieta Livre de Glúten , Glutens , Humanos , Peptídeos , Estudos ProspectivosRESUMO
BACKGROUND: Life-long removal of gluten from the diet is currently the only way to manage celiac disease (CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides (GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully established. AIM: To assess the performance of enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (PoCTs) for GIP excretion in CeD patients on gluten-free diet (GFD). METHODS: We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion (by ELISA in stool and PoCTs (commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study period. RESULTS: Forty-four patients were enrolled, of which 19 (43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were collected. Eleven out of 44 patients (25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases (Cohen´s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant (concomitantly positive or negative) in 67 out of 74 (90.5%) samples. Excretion of GIP was detected in 7 (8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary reports. CONCLUSION: GIP detects dietary transgressions in patients on long-term GFD, irrespective of the presence of symptoms. PoCT for GIP detection constitutes a simple home-based method for self-assessment of dietary indiscretions.
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Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Glutens/análise , Cooperação do Paciente , Peptídeos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Doença Celíaca/urina , Estudos Transversais , Autoavaliação Diagnóstica , Ensaio de Imunoadsorção Enzimática , Fezes/química , Feminino , Glutens/química , Glutens/imunologia , Glutens/metabolismo , Humanos , Eliminação Intestinal , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Peptídeos/imunologia , Peptídeos/metabolismo , Testes Imediatos , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity. GOALS: To investigate the potential mechanisms of a probiotic B. infantis Natren Life Start super strain on the mucosal expression of innate immune markers in adult patients with active untreated CD compared with those treated with B. infantis×6 weeks and after 1 year of gluten-free diet (GFD). METHODS: Numbers of macrophages and Paneth cells and α-defensin-5 expression were assessed by immunohistochemistry in duodenal biopsies. RESULTS: We showed that GFD decreases duodenal macrophage counts in CD patients more effectively than B. infantis. In contrast, B. infantis decreases Paneth cell counts and expression of α-defensin-5 in CD (P<0.001). CONCLUSIONS: The results identify differential innate immune effects of treatment with B. infantis compared with 1 year of GFD. Further studies are needed to investigate synergistic effects of GFD and B. infantis supplementation in CD.
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Bifidobacterium longum subspecies infantis/crescimento & desenvolvimento , Doença Celíaca/terapia , Dieta Livre de Glúten , Duodeno/metabolismo , Imunidade Inata , Imunidade nas Mucosas , Mucosa Intestinal/metabolismo , Probióticos/uso terapêutico , alfa-Defensinas/metabolismo , Adulto , Biomarcadores/metabolismo , Biópsia , Doença Celíaca/imunologia , Doença Celíaca/metabolismo , Doença Celíaca/microbiologia , Regulação para Baixo , Duodeno/imunologia , Duodeno/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Imuno-Histoquímica , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Celulas de Paneth/imunologia , Celulas de Paneth/metabolismo , Celulas de Paneth/microbiologia , Probióticos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To assess the evidence regarding the effect of time of gluten introduction and breastfeeding on the risk of developing celiac disease (CD). STUDY DESIGN: We included randomized controlled trials and observational studies evaluating the proper timing for introducing gluten to the infant diet, the appropriate quantity of gluten consumption at weaning, and the effect of breastfeeding on CD risk. Studies were located through the electronic databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), and System for Information on Grey Literature in Europe (SIGLE). Two independent authors collected the data. RESULTS: A total of 1982 studies were identified, 15 of which were eligible for data extraction. A meta-analysis was performed on 2 randomized controlled trials, 10 cohort studies, and 1 case-control study. There was a 25% increase in CD risk with late (>6 months) vs recommended (4-6 months) gluten introduction (risk ratio [RR], 1.25; 95% CI, 1.08-1.45). There was no significant effect of breastfeeding vs no breastfeeding on CD risk (OR, 0.55; 95% CI, 0.28-1.10), with substantial heterogeneity (I(2) = 92%) among studies. CONCLUSION: There is currently no evidence to support that early introduction of gluten to the infant diet increases the risk of CD; however, late introduction of gluten may be associated with increased risk of CD. More studies are needed that control for potential confounders and that evaluate environmental factors in low-risk families.