Pilot study protocol for determining differences in quantitative and functional aspects of dendritic cell subsets in early onset pre-eclampsia patients- a feasibility study for identification of biomarker(s) and immunotherapeutic target(s)

Abstract

Background: Pre-eclampsia (PE) is a pregnancy associated pro-inflammatory disorder. The only known treatment is to deliver the placenta and fetus. PE is clinically identified by hypertension and proteinuria post-20th week of gestation. Early onset pre-eclampsia (EOPE), a severe form of PE is defined as when the clinical symptoms are observed before 34 weeks of gestation. There are no definite biomarkers available for early diagnosis of EOPE. Human dendritic cell (DC) subsets (CD1c+, CD141+ myeloid DCs and plasmacytoid DCs) are intricately involved with the process of inflammation and are significantly altered (quantitatively and functionally) in several proinflammatory disorders. These changes offer value for monitoring DC subsets as potential biomarker(s) and as targets for immunotherapeutic treatment. DC subsets play a critical role in normal pregnancy by mediating efficient migration and invasion of trophoblasts and maintaining anti-inflammatory environment of immunotolerance. In contrast, the status of DC subsets in the proinflammatory microenvironment of EOPE pregnancy requires thorough evaluation. In this direction, the designed study protocol aims to understand how DC subsets are altered (quantitatively and functionally) in EOPE patients, compared to normal pregnant women. Methods: Study protocol is designed to determine changes in the profile of DC subsets in the blood and decidua of EOPE patients by multiparametric flow cytometry approach. Normal pregnant women are included as controls.Discussion: Human DC subsets are altered both quantitatively and functionally in the pro-inflammatory microenvironment. EOPE is a pro-inflammatory disorder and changes in the composition and function of DC subsets in these patients, compared to normal pregnant women is unclear. In this study, the blood sample-based analysis will determine the feasibility for identification of DC subsets associated novel immune biomarkers for early diagnosis of EOPE. In addition, changes in the profile of DC subsets in the decidua of EOPE patients will determine the feasibility for developing novel immunotherapeutic strategies targeting distinct DC subsets or their products for the treatment of EOPE. Overall, the current study protocol and findings will help develop future large scale, prospective design clinical trials focussing on formulating strategies for early diagnosis and treatment of EOPE among pregnant women.