TY - JOUR
T1 - Profiling of peripheral blood B-cell transcriptome in children who developed coeliac disease in a prospective study
AU - Oras, Astrid
AU - Kallionpää, Henna
AU - Suomi, Tomi
AU - Koskinen, Satu
AU - Laiho, Asta
AU - Elo, Laura L.
AU - Knip, Mikael
AU - Lahesmaa, Riitta
AU - Aints, Alar
AU - Uibo, Raivo
AU - DIABIMMUNE Study Group
N1 - Publisher Copyright:
© 2023
PY - 2023/2
Y1 - 2023/2
N2 - 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).
AB - 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).
KW - B-cells
KW - Coeliac disease
KW - High-throughput mRNA sequencing
UR - http://www.scopus.com/inward/record.url?scp=85147379705&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2023.e13147
DO - 10.1016/j.heliyon.2023.e13147
M3 - Article
AN - SCOPUS:85147379705
SN - 2405-8440
VL - 9
JO - Heliyon
JF - Heliyon
IS - 2
M1 - e13147
ER -