Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05294952 |
| Other study ID # |
zisdas |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2025 |
| Est. completion date |
November 4, 2025 |
Study information
| Verified date |
February 2024 |
| Source |
Assiut University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Preeclampsia is a form of hypertensive pregnancy disorder with multiorgan involvement. It is
characterized by new-onset hypertension and proteinuria after 20 weeks' gestation in a woman
whose blood pressure was normal before pregnancy. The condition may be serious and is a
leading cause of preterm birth (before 37 weeks of pregnancy). If it is severe enough it may
affect the brain function, causing seizures or coma, this is called eclampsia
Description:
T lymphocytes, as well as their regulatory subpopulations could possibly possess a part in PE
. The changes in T cell subsets that may be seen in preeclampsia include low Treg activity, a
shift toward Th1 responses, and the presence Th17 lymphocytes. B cells can participate in the
pathophysiology of preeclampsia by producing autoantibodies against adrenoreceptors and
autoantibodies that bind the AT1-R (angiotensin II type I receptor)
TH17 cells are a distinctive lineage of TCD4+ cells, which are distinguished by producing a
number of effective molecules such as IL-17, which is the most important cytokine produced by
these cells . IL-17 is capable of inducing the production of several cytokines, such as tumor
necrosis factor alpha (TNF-α) and IL-1β which possess significant parts in PE pathophysiology
.
Regulatory T lymphocytes CD4+ CD25bright are known to play an important role in the
development and maintenance of tolerance in peripheral tissues . They express high level of
CD25 (IL-2Ra) as well as cytotoxic T-lymphocyte antigen 4 (CTLA4) and the transcription
factor Foxp3 .
It was proposed that regulatory T cells (Tregs) are responsible for mediating maternal
tolerance for the fetus and their counts were found to be higher in normal pregnancies
However, the role of T reg cells in the development of preeclampsia remains controversial,
being decreased in some studies .) and of comparable frequencies to normal pregnancy in
others (Hu et, 2008). Tregs suppress maternal immune cells through the secretion of
inhibitory cytokines, such as interleukin (IL)-10 and transforming growth factor beta (TGF-β)
.
systemic endothelial dysfunction, such as disturbed coagulation function, could be
intensified through immune activation, resulting in inflammation and the disturbance of
regulatory T (Treg) and Th17 cell balance, and contributing to further activation of the
maternal immune responses .
Co-inhibitory-receptors such as CTLA-4 (cytotoxic T-lymphocyte-associated protein , LAG-3
(lymphocyte activation gene 3; or CD223), TIM-3 (T-cell immunoglobulin and mucin
domain-containing 3), PD-1 (PDCD1; programmed cell death 1), and TIGIT (T-cell immunoreceptor
with Ig and ITIM domains) are key factors in maintaining immune homeostasis and play a
central role in regulating autoimmune diseases .
These receptors regulate T-cell responses by inhibiting effector T-cell activation directly
by promoting the suppressive function of regulatory T-cells (Tregs) and affecting antigen
presentation. These cell surface molecules are expressed on activated immune cells (T-cells,
B cells, natural killer [NK] cells, some myeloid cells) that regulate the inflammatory and
autoimmune responses through a negative feedback mechanism. Malfunction of their crucial role
or decreased receptor levels can lead to excessive immune activation and autoimmunity .
While augmented effector T-cell activation plays a major role in preeclampsia pathogenesis,
insufficient co-inhibitory signals might promote preeclampsia development and progression.
Some studies have also shown that multiple co-inhibitory-molecules, e.g., TIM-3, LAG-3, and
TIGIT, predominantly regulate the effector T-cell responses within the tissue where their
responses are executed . Based on the previous findings on the important role of the
co-inhibitory molecules in regulating autoimmunity and cancer immunity, it might be assumed
that they also play a role in preeclampsia development and/or progression.
