Profiling of peripheral blood B-cell transcriptome in children who developed coeliac disease in a prospective study

Astrid Oras; Henna Kallionpää; Tomi Suomi; Satu Koskinen; Asta Laiho; Laura L Elo; Mikael Knip; Riitta Lahesmaa; Alar Aints; Raivo Uibo; DIABIMMUNE Study Group

doi:10.1016/j.heliyon.2023.e13147

Profiling of peripheral blood B-cell transcriptome in children who developed coeliac disease in a prospective study

Heliyon. 2023 Jan 21;9(2):e13147. doi: 10.1016/j.heliyon.2023.e13147. eCollection 2023 Feb.

Authors

Astrid Oras¹, Henna Kallionpää², Tomi Suomi^{2

3}, Satu Koskinen², Asta Laiho^{2

3}, Laura L Elo^{2

3

4}, Mikael Knip^{5

6

7}, Riitta Lahesmaa^{2

3}, Alar Aints¹, Raivo Uibo¹; DIABIMMUNE Study Group

Affiliations

¹ Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia.
² Turku Bioscience Centre, University of Turku and Åbo Akademi University, Finland.
³ InFLAMES Research Flagship Center, University of Turku, Turku, Finland.
⁴ Institute of Biomedicine, University of Turku, Finland.
⁵ Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁶ Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁷ Center for Child Health Research, Tampere University Hospital, Tampere, Finland.

Abstract

Background: In coeliac disease (CoD), the role of B-cells has mainly been considered to be production of antibodies. The functional role of B-cells has not been analysed extensively in CoD.

Methods: We conducted a study to characterize gene expression in B-cells from children developing CoD early in life using samples collected before and at the diagnosis of the disease. Blood samples were collected from children at risk at 12, 18, 24 and 36 months of age. RNA from peripheral blood CD19⁺ cells was sequenced and differential gene expression was analysed using R package Limma.

Findings: Overall, we found one gene, HNRNPL, modestly downregulated in all patients (logFC -0·7; q = 0·09), and several others downregulated in those diagnosed with CoD already by the age of 2 years.

Interpretation: The data highlight the role of B-cells in CoD development. The role of HNRPL in suppressing enteroviral replication suggests that the predisposing factor for both CoD and enteroviral infections is the low level of HNRNPL expression.

Funding: EU FP7 grant no. 202063, EU Regional Developmental Fund and research grant PRG712, The Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research (SyMMyS) 2012-2017, grant no. 250114) and, AoF Personalized Medicine Program (grant no. 292482), AoF grants 292335, 294337, 319280, 31444, 319280, 329277, 331790) and grants from the Sigrid Jusélius Foundation (SJF).

Keywords: B-cells; Coeliac disease; High-throughput mRNA sequencing.