GSE185503
Profiling of peripheral blood B-cell transcriptome in children who developed coeliac disease in a prospective study
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. Overall design: In the present case-control study we set out to investigate changes in B-cell gene expression in genetically predisposed children, prospectively followed from birth until the age of 3 years, who developed celiac disease (CoD) during follow-up. The study material includes PBMC samples from 12 children with HLA-conferred susceptibility to CoD from the international DIABIMMUNE Study. The subjects were matched with controls for sex, HLA DR/DQ genotype, country of birth, and date of birth. Six of them developed CoD during the study period (CoD progressors) and six of them were controls and they did not develop any autoantibodies or CoD during first three years of life. CD19+ B cells were purified from PBMC samples collected at a maximum of four time points (12, 18, 24 and 36 months of age) and analysed with RNAseq.