Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies

Rheumatoid arthritis (RA), Systemic Lupus Erythematosus (SLE) are genetically the most closely related of the major rheumatic diseases as they share components of the type I IFN signalling pathway linked to treatment response and disease activity. One difference between the two is how they respond to pregnancy; while RA often improves, SLE is prone to flare. Multiple mechanisms contribute to immunological tolerance of the foetus during pregnancy. More research involving comparative analyses is needed, however, as understanding how pregnancy-related immune-modulation differs in RA and SLE can potentially lead to better treatment options. We provide data from a cohort of women with universal accessibility to health care that have been followed closely throughout their pregnancies, are well regulated and have low disease activity. We analysed samples both by bulk- and scRNA-seq, and ran a cell-type estimation, validated by flow cytometry, before combining this in a cell-type adjusted analysis. This novel comparative approach gives an improved resolution of expression profiles in RA and SLE pregnancies. 335 whole blood samples from 84 RA, SLE, and healthy controls before pregnancy, at each trimester, 6 weeks, 6 months, and 12 months postpartum were analysed. We ran bulk and single cell RNA analyses and then combined these for cell-type estimation, validated by flow cytometry. These results were then used in a cell-type adjusted analysis for an improved resolution of unrecognized gene expression changes associated with RA and SLE pregnancies. --------------------- Authors state: The raw data are personal sensitive data and cannot be submitted due to Norwegian legal constraints.