Predictors of Pregnancy Complications in Pregnant Women with Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disorder common in women in their reproductive years. SLE is associated with several serious pregnancy complications, such as fetal loss, preterm birth, intrauterine growth restriction, and most notably pre-eclampsia. Dysregulation of CD4+/CD25+/Foxp3+ regulatory T cell (T reg cells) and Transforming Growth Factor beta-1 (TGF-β1) are considered contributory factors. It is well established that T reg cells play an important role in immunologic self-tolerance, ensuring the suppression of pro-inflammatory T cells. They are also considered a fundamental prerequisite for successful placentation. TGF-β1 is an immunosuppressive cytokine involved in both T reg cell activation and maintenance of normal blood vessel structure. Work documented in this thesis sets out to test the hypothesis that women with SLE have dysregulated T reg cells and TGF-β1 resulting in an inability to increase T reg cells in pregnancy and increase susceptibility to premature arterial stiffness which may predispose to pregnancy complications. T reg cells were assessed by flow cytometry (CD4+/CD25+/Foxp3+), TGFβ1 by an activational immunoassay, and arterial stiffness, expressed as a stiffness index (SI), by pulse wave photoplethysmography. The results showed that the level of CD4+/CD25+/Foxp3+ T reg cells in non-pregnant women with SLE and pregnant women with SLE at 12 and 20 weeks gestation, was significant lower than healthy matched controls. Similarly, the level of TGF-β1 in non-pregnant women with SLE, and pregnant women with SLE in their first trimester of pregnancy, were reduced compared to equivalent healthy groups. A significant increase in SI in SLE pregnant women at 12 and 36 weeks gestation was also observed. These data propose an alteration in T reg cell numbers and TGF-β1 in patients with SLE, and an inability to expand these to normal levels in pregnancy. Additionally, raised arterial stiffness in SLE patients may mean these women are intrinsically prone to vascular complications in pregnancy; further contributing to the risk of pre-eclampsia and poor pregnancy outcome.

Date of Award	1 Jan 1824
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Ian Crocker (Supervisor)