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• W2917286895 abstract "Career situation of first and presenting author Student for a master or a PhD. Introduction Antigen-specific B cells (Ag-Bs) differentiate into distinct subsets upon activation: plasmablasts (pBs, CD19+IgD-CD71+CD38+CD20-) and memory B cells (mBs, CD19+IgD-CD71+CD38dimCD20+). The frequency of antigen-specific plasmablasts and memory B cells has been described to be altered in the blood of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) patients. Emerging evidence suggests that blood immune cells from RA and SLE patients exhibit different metabolic requirements and profiles when compared to healthy controls (HC). However, the metabolic configurations of these two Ag-Bs subsets in RA and SLE patients are yet to be described. Objectives In the present study we aimed to characterize the gene expression of key metabolic enzymes in mBs and pBs from RA and SLE patients. Methods Blood samples were obtained from 5 RA, 2 SLE and 3 HC donors. B cells were isolated and sorted into pBs and mBs populations. The gene expression of key metabolic enzymes was assessed by qPCR in both populations. The target genes analyzed were HIF1A, HK2, LDHA, MYC (glycolysis), CPT1A (fatty acid oxidation), SREBF1 (lipid synthesis) and PRKAA1 (mTOR inhibitor). Results When comparing to HC there was a higher expression of: HIF1A, LDHA, MYC, PRKAA1 in RA mBs; HIF1A, HK2, LDHA, SREBF1 in RA pBs; HIF1A, HK2, LDHA, CPT1A, SREBF1 in SLE mBs; MYC and PRKAA1 in SLE pBs. When the gene expression was compared between RA and SLE patients, SLE mBs had a higher expression of HK2, CPT1A and SREBF1 while SLE pBs exhibited higher levels of MYC and PRKAA1 expression. Thus, the observed results suggest that RA mBs, RA pBs and SLE mBs exhibit a glycolytic profile when compared to HC. SLE mBs also seem to have higher fatty acid oxidation and lipid synthesis levels when comparing to HC and RA mBs. The higher expression of SREBF1 in RA pBs could also indicate that lipid synthesis is upregulated in this subset. Interestingly, the results in SLE pBs suggest that all the analyzed metabolic pathways are downregulated when comparing to HC and RA pBs. Finally, since PRKAA1 is upregulated in RA mBs and SLE pBs one might hypothesize that inhibition of mTOR is greater in these subsets. Conclusions The size of our sample is the principal limitation in this study and therefore we aim to increase it. Nevertheless, these preliminary results seem to indicate that antigen-specific B cells exhibit marked glycolytic profiles in RA and SLE patients. These results are expected in RA given the highly glycolytic requirements of T cells in this disease. Our study demonstrates that B cell metabolism should be characterized in depth in both RA and SLE. Disclosure of Interest None declared." @default.
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• W2917286895 date "2019-03-01" @default.
• W2917286895 modified "2023-09-27" @default.
• W2917286895 title "P001 Differential expression of key metabolic genes in antigen-specific B cell subsets in rheumatoid arthritis and systemic lupus erythematosus" @default.
• W2917286895 doi "https://doi.org/10.1136/annrheumdis-2018-ewrr2019.1" @default.
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