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Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study
Raquel Ríos León1, Laura Crespo Pérez1, Enrique Rodríguez de Santiago1,2
1a Department of Gastroenterology and Hepatology , Hospital Universitario Ramón y Cajal, University of Alcalá , Madrid , Spain.
Insights
Seronegative celiac disease (CD) presents unique diagnostic challenges. This study found seronegative CD is associated with more HLA-DQ8 genes and milder duodenal biopsy findings compared to seropositive CD.
Area of Science:
- Gastroenterology
- Immunology
- Genetics
Background:
- Seronegative celiac disease (CD) presents diagnostic difficulties.
- Distinguishing seronegative from seropositive CD is crucial for accurate diagnosis and management.
- Understanding the distinct characteristics of seronegative CD can improve patient outcomes.
Purpose of the Study:
- To characterize seronegative celiac disease.
- To identify key differences between seronegative and seropositive CD patients.
- To evaluate diagnostic tools for seronegative CD.
Main Methods:
- Retrospective cohort study of adult CD patients diagnosed between 1980-2017.
- Compilation of clinical, analytical, histological, genetic, and immunophenotypic data.
- Definition of seronegative CD included negative serology (anti-tissue transglutaminase IgA, EMA), positive HLA-DQ2/DQ8, clinical symptoms, abnormal biopsy, and GFD response.
Main Results:
- Seronegative CD was found in 8.3% of patients (26/315).
- Seronegative CD patients showed higher prevalence of autoimmune thyroiditis, HLA-DQ8 heterozygosity, and Marsh I lesions.
- Duodenal immunophenotype by flow cytometry and refractory CD rates were similar between seropositive and seronegative groups.
Conclusions:
- Seronegative CD is distinguished by genetic factors (increased HLA-DQ8) and milder histological findings (less atrophy).
- Intestinal intraepithelial immunophenotyping via flow cytometry is a valuable diagnostic aid for seronegative CD.
- Further research into the specific mechanisms and management of seronegative CD is warranted.
Abstract:
Background: Seronegative celiac disease (CD) poses a diagnostic challenge. Aims: Characterize and identify differences between seronegative and seropositive CD. Patients and methods: Retrospective cohort study examining adult patients diagnosed with CD (1980-2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression. Results: Of 315 CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% vs. 9.7%, p = .016), HLA-DQ8 heterozygosity (23.1% vs. 2.5%, p ˂ .001) and Marsh I lesion (34.6% vs. 3.7%, p ˂ .001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD. Conclusions: Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.
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