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Seronegative celiac disease: where is the specific setting?

Enzo Ierardi1, Giuseppe Losurdo1, Domenico Piscitelli1

  • 1Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Italy.

Gastroenterology and Hepatology From Bed to Bench
|May 1, 2015
PubMed
Summary

Seronegative celiac disease (SNCD) presents diagnostic challenges due to negative antibody tests despite positive histology. Mucosal immune complex formation may explain this seronegativity, highlighting the need for improved diagnostic tools.

Keywords:
DiagnosisImunoglobulinsSerologySeronegative celiac diseaseTissue transglutaminase

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Area of Science:

  • Gastroenterology
  • Immunology
  • Genetics

Background:

  • Celiac Disease (CD) diagnosis requires integrating pathological, serological, genetic, and clinical data, often posing challenges.
  • Seronegative Celiac Disease (SNCD) is identified by negative anti-tissue transglutaminase (tTG) antibodies with positive duodenal biopsy histology (e.g., intra-epithelial lymphocytes, villous atrophy) and specific human leukocyte antigen (HLA) haplotypes (DQ2/DQ8).

Purpose of the Study:

  • To explore the underlying mechanisms of seronegativity in SNCD.
  • To discuss the diagnostic challenges and management controversies surrounding SNCD.
  • To emphasize the need for a reliable diagnostic test for SNCD.

Main Methods:

  • Review of existing literature on SNCD diagnosis and pathophysiology.
  • Analysis of serological, histological, and genetic markers in SNCD.
  • Discussion of potential mechanisms for antibody sequestration in the mucosa.

Main Results:

  • SNCD is characterized by mucosal deposits of tTG/anti-tTG immune complexes, potentially hindering antibody detection in serum.
  • Impaired plasma cell maturation and antibody production, common in immunoglobulin deficiencies, may also contribute to seronegativity in SNCD.
  • SNCD is frequently observed in individuals with immunoglobulin deficiencies.

Conclusions:

  • The management of SNCD, including the utility of a gluten-free diet (GFD), remains debated and may depend on clinical presentation and HLA status.
  • A definitive diagnostic test for SNCD is currently lacking, yet highly desirable for accurate diagnosis and management.
  • Further research is needed to develop reliable diagnostic methods for SNCD.