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©The Author(s) 2021.
World J Gastroenterol. Oct 7, 2021; 27(37): 6306-6321
Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6306
Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6306
Table 1 Studies that have used gluten immunogenic peptides determination in stool and/or urine for gluten-free diet monitoring
| Ref. | Design | Study population | Intervention | Main results | ||
| Comino et al[8] | Prospective, multicenter, observational study | 184 adult and pediatric CeD patients | Fecal GIP ELISA, serology, questionnaires, and symptoms to evaluate adherence to the GFD | GIP-positive results were found in 12%-28% of children < 12 years-old, 30% in > 13 years-old females and 60% in > 13 years-old males. Low correlation of anti-tTG and anti-DGP markers and poor adherence to the GFD | ||
| Moreno et al[9] | Randomized controlled study | 58 adult and pediatric CeD patients and 76 healthy controls | Urine GIP LFIA test, serology, and duodenal biopsy to evaluate adherence to the GFD | About 50% CeD patients were GIP-positive. High correlation of GIP quantifiable concentration in urine with persistent villus atrophy in treated CeD patients (n = 25). No correlation between serology and mucosal damage | ||
| Gerasimidis et al[39] | Cross-sectional study cohort for a subgroup | 63 pediatric CeD patients | Fecal ELISA GIP test, serology, and questionnaires to evaluate gluten intake during diagnosis and adherence to the GFD after diagnosis | GIP-positive results in 95% of de novo patients with CeD during diagnosis. GIP-positive results were found in 17% and 27% of patients after 6 and 12 months of the beginning of the GFD, respectively. GIP-positive results were found in 16%, 16%, and 14% of patients considered compliant according to the Biagi score, tTG, and clinical assessment, respectively | ||
| Comino et al[40] | Prospective, multicenter, observational study | 64 pediatric CeD patients | Fecal GIP ELISA, serology, questionnaires, and symptoms to evaluate adherence to the GFD after diagnosis | Most children (97%) were GIP-positive at diagnosis. A decrease of GIP detection was observed on a GFD, but the rate of GIP-positive results increased from 13% at 6 months to 25% at 24 months. Anti-tTG antibody levels showed low sensitivity to identify patients with GIP-positive results. Dietitian assessment was only moderately correlated with GIP detection | ||
| Costa et al[41] | Cross-sectional study and prospective cohort | 44 adult CeD patients | Fecal GIP ELISA, stool and urine LFIA GIP tests, serology, questionnaires, and symptoms to evaluate adherence to the GFD | 25% of patients had at least one GIP-positive test, 32% in asymptomatic patients and 15.8% in symptomatic patients. Dietary assessment estimated gluten intake in only 50% of GIP-positive samples. Anti-tTG and anti-DGP positive results in 3/12 and 6/12 of GIP-positive cases, respectively | ||
| Silvester et al[29,30] | Prospective longitudinal study | 18 adult CeD patients | Monitoring GFD adherence by collection of daily food, stool, and urine samples for the analysis of GIP content, and relationship with duodenal biopsy, serology, questionnaires, and symptoms | GIP were detected in 66,7% patients. No significant correlation was found between gluten ingestion and non-invasive measures of GFD adherence. Most patients with normal anti-tTG had ≥ 1 GIP-positive sample (64%), 2/3 of these had persistent villous atrophy (Marsh 3a) and 2/3 of those with all GIP-negative samples had normal villous architecture (Marsh 0-1) but 4/6 with Marsh 0 had detectable gluten in ≥ 1 sample | ||
| Ruiz-Carnicer et al[23] | Prospective observational study | 22 newly diagnosed CeD patients, 77 CeD patients following a GFD and 13 healthy volunteers | Urine LFIA GIP test to evaluate adherence to the GFD and comparison with serology, clinical manifestations, dietary questionnaire, and histological results | Mucosal damage (Marsh II-III) was found in 24% of CeD patients, 94%of these had ≥ 1 GIP urine sample. 60-80% of these were asymptomatic, had negative serologic results and were compliant with treatment regarding the dietary questionnaire. GIP-negative results were found in 97% of the patients without mucosal damage | ||
| Fernandez-Miaja et al[22] | Cross-sectional study | 80 pediatric CeD patients | Relationship of fecal LFIA GIP for GFD monitoring GFD with CDAT, serology and sociodemographic and clinical data | Acceptable agreement was found between GIP detection and CDAT questionnaire (92.5% and 86.3% adherence rate, respectively). Most patients (83.3%) with GIP-positive results had negative anti-tTG antibodies | ||
| Porcelli et al[42] | Cross-sectional study | 25 CeD patients | Assessment of compliance with the GFD using Fecal GIP ELISA testing, the Biagi questionnaire, evaluation of symptoms and serology | GIP-positive results were found in 4 patients, 2 of these complied with the GFD according to the Biagi questionnaire. All GIP-negative patients were asymptomatic. Levels of anti-tTG antibodies were significantly higher in GIP-positive patients than in GIP-negative patients | ||
| Roca et al[43] | Prospective, cross-sectional study | 43 pediatric CeD patients at follow-up (Group 1) and 18 at diagnosis (Group 2) | Fecal GIP ELISA and LFIA analysis to monitor in real life the adherence to GFD Comparison to food record questionnaire and serology | Group 1: GIP-positive results were found in of 34.9% patients by ELISA (46,7% also by LFIA). 48.8% of patients had positive anti-tTG antibodies (4 reported symptoms) and 10 of these had GIP-positive results by ELISA (70% also by LFIA) (2 reported symptoms). All the transgressions detected by food record were also detected with GIP | ||
| Porcelli et al[44] | Cross-sectional study | 55 CeD patients: 27 adults and 28 children | Assessment of compliance with the GFD using Fecal GIP ELISA, the Biagi questionnaire, evaluation of symptoms and serology | GIP-positive results were found in 8 patients, 71.4% of these were asymptomatic and 37.5% had raised anti-tTG antibodies. A significant association was found between the Biagi score and GIP-positive results but according to the Biagi score, 57.1% of GIP-positive patients followed the diet strictly and 5.4% of GIP-negative subjects did not comply with the diet | ||
| Laserna-Mendieta et al[45] | Prospective observational study | 97 adolescent and adult CeD patients | Evaluation of the sensitivity and specificity of fecal GIP LFIA test to detect duodenal lesions in CeD patients on a GFD and comparison to serology and questionnaires | Compared to the duodenal histology, GIP LFIA test showed similar sensitivity (33%) and specificity (81%) to anti-tTG antibodies. No relationship was found between GIP and questionnaires but an association between GIP and patients’ self-reported gluten consumption was seen | ||
| Stefanolo et al[24] | Prospective observational study | 53 adult CeD patients | Fecal GIP ELISA and urine LFIA GIP test, anti-tTG, anti-DGP, and questionnaires to evaluate adherence to the GFD in symptomatic and asymptomatic patients | At least one GIP-positive result in 88.7% of patients for the 4 wk period. Patients who had symptoms had elevated GIP levels for more weeks than patients who did not have these symptoms (P < 0.05). Correlation was found between GIP and anti-DGP antibodies but not with levels of anti-tTG antibodies | ||
| Fernández-Bañares et al[46] | Multicenter prospective observational study | 76 adult CeD patients | Fecal GIP ELISA, anti-tTG, questionnaires and symptomatology to evaluate villous atrophy persistence after 2 years on a GFD | Persistent villous atrophy was present in 53% of patients at follow-up, 72% of these were asymptomatic and 75% had negative anti-tTG antibodies. Most patients were adherent to the GFD according to the dietary evaluation. In contrast, GIP-positive results were found in ≥ 1 fecal sample of 77% of patients with villous atrophy and in 60% of patients with mucosal recovery | ||
Table 2 Available immunomethods to detect gluten immunogenic peptides in stool and urine
Table 3 Parametrical features of the gluten immunogenic peptides excretion using lateral flow immunoassay and enzyme-like immunosorbent assay methods
| Specifications for the determination of GIP excretion after gluten intake | Sample | Time ranges (h) | Gluten source (amount) | Method |
| Shortest time to detect GIP | Urine | 3-9 | GCD (> 2 g) | LFIA [9,29,30] |
| Stool→ | < 24 | GCD (> 2 g) | LFIA; ELISA[43] | |
| Longest time to detect GIP | Urine | 36 | GCD (> 2 g) | LFIA[9,29,30] |
| Stool | > 72 | GCD (> 2 g) | LFIA; ELISA[29,30,43] | |
| Minimal gluten intake to detect excreted GIP | Urine | > 40-500 mg/d; | LFIA; SPE + LFIA[9,41] | |
| 25-50 mg | ||||
| Stool | > 40 mg/d | ELISA, LFIA[41,43] |
Table 4 Determination of gluten-free diet non-adherence using different tools, n (%)
| Ref. | Stool GIP+ | Urine GIP+ | anti-tTG+ | anti-DGP+ | Questionnaires1 | Symptoms | Duodenal biopsy (Marsh II/III) |
| Comino et al[8] | 56 (30) | - | 32 (18) | 11 (6) | 25 (18) | 9 (5) | - |
| Moreno et al[9] | - | 12 (48) | 4 (16) | - | - | 7 (28) | |
| Gerasimidis et al[39] | 11 (19) | - | 12 (20) | - | 4 (6) | - | - |
| Comino et al[40] | 6 (25) | - | 7 (20) | 0 (0) | - | - | - |
| Costa et al[41] | 11 (25) | 3 (7) | 9 (21) | 18 (45) | 18 (41) | 19 (43) | - |
| Silvester et al[29,30] | 5 (28) | 8 (44) | 7 (39) | - | 4 (22) | 8 (44) | 10 (56) |
| Ruiz-Carnicer et al[23] | - | 44 (58) | 9 (12) | - | 14 (23) | 18 (23) | 18 (24) |
| Fernández-Miaja et al[22] | 6 (8) | - | 3 (4) | - | 10 (13) | - | - |
| Roca et al[43] | 15 (35) | - | 22 (51) | - | 4 (9) | 4 (9) | - |
| Porcelli et al[44] | 8 (15) | - | 3 (6) | - | 5 (11) | 16 (34) | - |
| Laserna-Mendieta et al[45] | 22 (23) | - | 11 (12) | - | 17 (18) | - | 6 (28) |
| Stefanolo et al[24] | 33 (62) | 37 (70) | 22 (42) | 25 (47) | - | 18 (34) | - |
| Fernández-Bañares et al[46] | 53 (70) | - | 17 (22) | - | 6 (8) | 15 (20) | 40 (53) |
Table 5 Rate of transgressions in the gluten-free diet using different tools in presence/absence of mucosal atrophy by duodenal biopsy, n (%)
| Ref. | GIP+ (Stool and/or urine) | Serology+ | Questionnaires1 | Symptoms |
| Duodenal biopsy (Marsh II/III) | ||||
| Moreno et al[9] | 7 (100) | 2 (29) | - | - |
| Silvester et al[29,30] | 8 (80) | - | - | - |
| Ruiz-Carnicer et al[23] | 17 (94) | 7 (39) | 6 (43) | 4 (22) |
| Laserna-Mendieta et al[45] | 2 (33) | 2 (33) | 3 (50) | - |
| Fernández-Bañares et al[46] | 31 (78) | 10 (25) | 1 (3) | 11 (28) |
| Duodenal biopsy (Marsh 0/I) | ||||
| Moreno et al[9] | 5 (28) | 2 (11) | - | - |
| Silvester et al[29,30] | 4 (50) | - | - | - |
| Ruiz-Carnicer et al[23] | 27 (47) | 2 (3) | 8 (17) | 14 (24) |
| Laserna-Mendieta et al[45] | 20 (22) | 9 (10) | 77 (85) | - |
| Fernández-Bañares et al[46] | 22 (61) | 7 (19) | 5 (14) | 4 (11) |
- Citation: Coto L, Mendia I, Sousa C, Bai JC, Cebolla A. Determination of gluten immunogenic peptides for the management of the treatment adherence of celiac disease: A systematic review. World J Gastroenterol 2021; 27(37): 6306-6321
- URL: https://www.wjgnet.com/1007-9327/full/v27/i37/6306.htm
- DOI: https://dx.doi.org/10.3748/wjg.v27.i37.6306