T cell receptor repertoire as a potential diagnostic marker for celiac disease

Ying Yao; Asima Zia; Ralf Stefan Neumann; Milena Pavlovic; Gabriel Balaban; Knut E A Lundin; Geir Kjetil Sandve; Shuo-Wang Qiao

doi:10.1016/j.clim.2020.108621

T cell receptor repertoire as a potential diagnostic marker for celiac disease

Clin Immunol. 2021 Jan:222:108621. doi: 10.1016/j.clim.2020.108621. Epub 2020 Nov 13.

Authors

Ying Yao¹, Asima Zia², Ralf Stefan Neumann¹, Milena Pavlovic³, Gabriel Balaban³, Knut E A Lundin⁴, Geir Kjetil Sandve⁵, Shuo-Wang Qiao⁶

Affiliations

¹ Department of Immunology, Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Norway.
² Department of Immunology, Institute of Clinical Medicine, University of Oslo, Norway.
³ Department of Informatics, University of Oslo, Norway.
⁴ K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Norway.
⁵ K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Norway; Department of Informatics, University of Oslo, Norway.
⁶ Department of Immunology, Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Norway. Electronic address: [email protected].

PMID: 33197618
DOI: 10.1016/j.clim.2020.108621

Abstract

An individual's T cell repertoire is skewed towards some specificities as a result of past antigen exposure and subsequent clonal expansion. Identifying T cell receptor signatures associated with a disease is challenging due to the overall complexity of antigens and polymorphic HLA allotypes. In celiac disease, the antigen epitopes are well characterised and the specific HLA-DQ2-restricted T-cell repertoire associated with the disease has been explored in depth. By investigating T cell receptor repertoires of unsorted lamina propria T cells from 15 individuals, we provide the first proof-of-concept study showing that it could be possible to infer disease state by matching against a priori known disease-associated T cell receptor sequences.

Keywords: CD4+ T cells; Celiac disease; Disease inference; High-throughput sequencing; TCR repertoire.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Biomarkers
Celiac Disease / diagnosis*
Celiac Disease / immunology*
Epitopes, T-Lymphocyte / immunology*
HLA-DQ Antigens / genetics
HLA-DQ Antigens / immunology
Humans
Lymphocyte Activation / immunology
Middle Aged
Mucous Membrane / cytology
Mucous Membrane / immunology
Receptors, Antigen, T-Cell / immunology*
Young Adult

Substances

Biomarkers
Epitopes, T-Lymphocyte
HLA-DQ Antigens
HLA-DQ2 antigen
Receptors, Antigen, T-Cell