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Application of Deamidated Gliadin Antibodies in the Follow-Up of Treated Celiac Disease.

de Chaisemartin L, Meatchi T, Malamut G, Fernani-Oukil F, Hosking F, Rault D, Bellery F, Cellier C, Dragon-Durey MA - PLoS ONE (2015)

Bottom Line: For all deamidated gliadin and transglutaminase tests, we found that a positive result was significantly associated with persistence of intestinal VA, with a diagnostic efficacy up to 80%.Using a test positivity pattern analysis, we were also able to identify several groups of patients with distinct antibody profiles that showed significant differences in intestinal damage and diet compliance.Altogether, these results show that deamidated gliadin antibodies are strongly correlated with VA and should be considered valuable tools in CD follow-up and that multiplex serologic analysis for treated CD represents a promising tool for personalized patient management.

View Article: PubMed Central - PubMed

Affiliation: Immunology Department, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM UMR 996, Paris Sud University, Châtenay-Malabry, France.

ABSTRACT

Introduction: The role of serological tests such as IgA anti-transglutaminase autoantibodies has become increasingly important in celiac disease (CD) diagnosis. However, the efficiency of these tests for patient follow-up is controversial. We investigated the correlation of 12 different serological tests, including recent deamidated gliadin and actin IgA tests, with villous atrophy (VA) in a retrospective cohort of treated celiac patients.

Materials and methods: Serum samples were collected from 100 treated CD patients who had intestinal biopsy in the course of their follow-up. Antibodies against transglutaminase, deamidated gliadin peptides, and native gliadin were measured, along with IgA anti-actin. The biopsy slides were all blind-reviewed and scored according to Marsh classification.

Results: For all deamidated gliadin and transglutaminase tests, we found that a positive result was significantly associated with persistence of intestinal VA, with a diagnostic efficacy up to 80%. Furthermore, antibodies titers directly correlated with the degree of VA, indicating a strong link between disease activity and presence of antibodies in the serum. Interestingly, the tests with the highest association with persistent VA were those for deamidated gliadin IgG. Using a test positivity pattern analysis, we were also able to identify several groups of patients with distinct antibody profiles that showed significant differences in intestinal damage and diet compliance.

Conclusions: Altogether, these results show that deamidated gliadin antibodies are strongly correlated with VA and should be considered valuable tools in CD follow-up and that multiplex serologic analysis for treated CD represents a promising tool for personalized patient management.

No MeSH data available.


Related in: MedlinePlus

Analysis of antibody positivity profile.(a): Percentage of positive tests (Mean ±SEM) for each patient group. (b): Unsupervised hierarchical clustering of serological data. Each square represents the result of one test (lines) for one patient (columns), while its color represents the positivity level of the test. The test titers were normalized by calculating the ratio between titer and cut-off. Antibody titers close to cut-off values are represented by yellow squares, titers below cut-off range from yellow (cut-off) to green (very low titers) and titers above cut-off range from yellow (cut-off) to red (very high titers). (c): Proportion of histological scores in the patient clusters. (d): Unsupervised hierarchical clustering of serological data restricted to patients with partial atrophy (Marsh 3a).
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pone.0136745.g003: Analysis of antibody positivity profile.(a): Percentage of positive tests (Mean ±SEM) for each patient group. (b): Unsupervised hierarchical clustering of serological data. Each square represents the result of one test (lines) for one patient (columns), while its color represents the positivity level of the test. The test titers were normalized by calculating the ratio between titer and cut-off. Antibody titers close to cut-off values are represented by yellow squares, titers below cut-off range from yellow (cut-off) to green (very low titers) and titers above cut-off range from yellow (cut-off) to red (very high titers). (c): Proportion of histological scores in the patient clusters. (d): Unsupervised hierarchical clustering of serological data restricted to patients with partial atrophy (Marsh 3a).

Mentions: First, the percentage of positive tests was assessed for each patient and plotted against patient’s clinical status (Fig 3A). We observed that the percentage of positive tests progressively rose from 11% for CD patients with normal biopsies to 80% for patients with Marsh 3b-3c biopsies. These proportions were compared to those obtained for our 2 reference groups of non-celiac patients and untreated celiac patients (as described in the beginning of the Results section). When compared this way, treated CD patients with normal or subnormal biopsies (Marsh 0 and Marsh 1–2) were not significantly different from non-coeliac controls (p = 0.1) and treated CD patients with severe atrophy were not different from untreated CD patients. (p = 0.2).


Application of Deamidated Gliadin Antibodies in the Follow-Up of Treated Celiac Disease.

de Chaisemartin L, Meatchi T, Malamut G, Fernani-Oukil F, Hosking F, Rault D, Bellery F, Cellier C, Dragon-Durey MA - PLoS ONE (2015)

Analysis of antibody positivity profile.(a): Percentage of positive tests (Mean ±SEM) for each patient group. (b): Unsupervised hierarchical clustering of serological data. Each square represents the result of one test (lines) for one patient (columns), while its color represents the positivity level of the test. The test titers were normalized by calculating the ratio between titer and cut-off. Antibody titers close to cut-off values are represented by yellow squares, titers below cut-off range from yellow (cut-off) to green (very low titers) and titers above cut-off range from yellow (cut-off) to red (very high titers). (c): Proportion of histological scores in the patient clusters. (d): Unsupervised hierarchical clustering of serological data restricted to patients with partial atrophy (Marsh 3a).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554732&req=5

pone.0136745.g003: Analysis of antibody positivity profile.(a): Percentage of positive tests (Mean ±SEM) for each patient group. (b): Unsupervised hierarchical clustering of serological data. Each square represents the result of one test (lines) for one patient (columns), while its color represents the positivity level of the test. The test titers were normalized by calculating the ratio between titer and cut-off. Antibody titers close to cut-off values are represented by yellow squares, titers below cut-off range from yellow (cut-off) to green (very low titers) and titers above cut-off range from yellow (cut-off) to red (very high titers). (c): Proportion of histological scores in the patient clusters. (d): Unsupervised hierarchical clustering of serological data restricted to patients with partial atrophy (Marsh 3a).
Mentions: First, the percentage of positive tests was assessed for each patient and plotted against patient’s clinical status (Fig 3A). We observed that the percentage of positive tests progressively rose from 11% for CD patients with normal biopsies to 80% for patients with Marsh 3b-3c biopsies. These proportions were compared to those obtained for our 2 reference groups of non-celiac patients and untreated celiac patients (as described in the beginning of the Results section). When compared this way, treated CD patients with normal or subnormal biopsies (Marsh 0 and Marsh 1–2) were not significantly different from non-coeliac controls (p = 0.1) and treated CD patients with severe atrophy were not different from untreated CD patients. (p = 0.2).

Bottom Line: For all deamidated gliadin and transglutaminase tests, we found that a positive result was significantly associated with persistence of intestinal VA, with a diagnostic efficacy up to 80%.Using a test positivity pattern analysis, we were also able to identify several groups of patients with distinct antibody profiles that showed significant differences in intestinal damage and diet compliance.Altogether, these results show that deamidated gliadin antibodies are strongly correlated with VA and should be considered valuable tools in CD follow-up and that multiplex serologic analysis for treated CD represents a promising tool for personalized patient management.

View Article: PubMed Central - PubMed

Affiliation: Immunology Department, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM UMR 996, Paris Sud University, Châtenay-Malabry, France.

ABSTRACT

Introduction: The role of serological tests such as IgA anti-transglutaminase autoantibodies has become increasingly important in celiac disease (CD) diagnosis. However, the efficiency of these tests for patient follow-up is controversial. We investigated the correlation of 12 different serological tests, including recent deamidated gliadin and actin IgA tests, with villous atrophy (VA) in a retrospective cohort of treated celiac patients.

Materials and methods: Serum samples were collected from 100 treated CD patients who had intestinal biopsy in the course of their follow-up. Antibodies against transglutaminase, deamidated gliadin peptides, and native gliadin were measured, along with IgA anti-actin. The biopsy slides were all blind-reviewed and scored according to Marsh classification.

Results: For all deamidated gliadin and transglutaminase tests, we found that a positive result was significantly associated with persistence of intestinal VA, with a diagnostic efficacy up to 80%. Furthermore, antibodies titers directly correlated with the degree of VA, indicating a strong link between disease activity and presence of antibodies in the serum. Interestingly, the tests with the highest association with persistent VA were those for deamidated gliadin IgG. Using a test positivity pattern analysis, we were also able to identify several groups of patients with distinct antibody profiles that showed significant differences in intestinal damage and diet compliance.

Conclusions: Altogether, these results show that deamidated gliadin antibodies are strongly correlated with VA and should be considered valuable tools in CD follow-up and that multiplex serologic analysis for treated CD represents a promising tool for personalized patient management.

No MeSH data available.


Related in: MedlinePlus