The use of peripheral blood mononuclear cells in celiac disease diagnosis and treatment

ABSTRACT

Introduction: Celiac disease is characterized by an abnormal immune activation driven by the ingestion of gluten from wheat, barley, and rye. Gluten-specific CD4⁺ T cells play an important role in disease pathogenesis and are detectable among peripheral blood mononuclear cells (PBMCs).

Areas covered: This review summarizes the use of celiac disease patient PBMCs in clinical applications focusing on their exploitation in the development of diagnostic approaches and novel drugs to replace or complement gluten-free diet.

Expert opinion: The most used PBMC-based methods applied in celiac disease research include ELISpot and HLA-DQ:gluten tetramer technology. ELISpot has been utilized particularly in research aiming to develop a celiac disease vaccine and in studies addressing the toxicity of different grains in celiac disease. HLA-DQ:gluten tetramer technology on the other hand initially focused on improving current diagnostics but in combination with additional markers it is also a useful outcome measure in clinical trials to monitor the efficacy of drug candidates. In addition, the technology serves well in the more detailed characterization of celiac disease-specific T cells, thereby possibly revealing novel therapeutic targets. Future studies may also reveal clinical applications for PBMC microRNAs and/or dendritic cells or monocytes present among PBMCs.

KEYWORDS:

• Celiac disease
• diagnostics
• ELISpot
• gluten
• HLA-DQ:gluten tetramer
• treatment

Article highlights

• A major challenge in current celiac disease diagnostic methods is their reliability only during ingestion of gluten. In addition, an active search for novel treatment options to replace gluten-free diet (GFD) is ongoing. Gluten-specific CD4⁺ cells present among peripheral blood mononuclear cells (PBMCs) are a distinguishing characteristic for the disease and could provide a useful tool for these purposes.

• The most commonly used methods utilizing celiac patients’ PBMCs include ELISpot and HLA-DQ:gluten tetramer technology.

• ELISpot has been utilized particularly in vaccine development and in the identification of minimally toxic grains. However, for optimal performance it requires a short gluten challenge.

• HLA-DQ:gluten tetramers have been tested for their usefulness in celiac disease diagnostics. In addition, the technology is useful in the deeper characterization of the celiac disease T cell repertoire, which may reveal future therapeutic targets. Moreover, when combined with evaluation of other markers the tetramers are suitable for monitoring drug efficacy in clinical trials.

Declaration of interest

K Kaukinen and K Lindfors are supported by the Academy of Finland and the Sigrid Juselius Foundation. K Kaukinen is also supported by the Competitive State Research Financing of the Expert Area of Tampere University Hospital, and the Development Fund for Agriculture and Forestry (Makera, Ministry of Agriculture and Forestry of Finland. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.