Raine, Charles David Anthony;
(2023)
Investigating the roles of regulatory T cells and lipid metabolism in ultrasound-defined disease activity of rheumatoid arthritis in pregnancy.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Rheumatoid arthritis (RA) is an inflammatory rheumatic disease that affects ~0.2 % of women of child-bearing age in the UK. Pregnancy has an overall ameliorative effect on RA disease activity, but around half of patients experience postpartum flare. The mechanism(s) of these phenomena remain uncertain. Previous studies of RA disease activity in pregnancy have used ‘joint counts’ such as the modified DAS28, but this measure has never been validated against a gold-standard such as musculoskeletal ultrasound (MSK-US), which is more sensitive for the detection of synovitis. Previous work has reported that the function of immunosuppressive regulatory T cells (Tregs), thought to be defective in RA, may be augmented in pregnancy-induced remission. Serum levels of lipids and sex hormones rise considerably in pregnancy and are immunologically active, including effects on Treg function, but neither have been studied in relation to RA disease activity. I hypothesised that (1) DAS28 would perform poorly compared to MSK-US in pregnancy and (2) pregnancy leads to restoration of defective Treg function in RA, which may be related to the effects of rising lipids and sex hormones. I recruited a prospective cohort of pregnant women with RA (n = 28) alongside non-pregnant RA and healthy controls. Patients underwent disease activity assessment with DAS28 and MSK-US and blood was taken for detailed Treg immunophenotyping, functional analysis and metabolomic profiling. Contrary to my hypothesis, DAS28 was a reliable measure of disease activity in pregnancy in comparison to MSK-US and Treg function was reduced in amelioration of RA (and increased in postpartum flare). Lipid metabolites (monounsaturated fatty acids, high- and very-low-density lipoproteins) but not sex hormones were associated with alteration of RA disease activity in pregnancy. My findings will contribute to the development of predictors of RA disease response in pregnancy and postpartum and thus improve future patient care.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating the roles of regulatory T cells and lipid metabolism in ultrasound-defined disease activity of rheumatoid arthritis in pregnancy |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10182137 |
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