Assessment of Natural Killer Cells in Unexplained Recurrent Pregnancy Loss

Assessment of Natural Killer Cells Activating and Inhibitors

To assess natural killer cells frequency and activation in cases of unexplained recurrent abortion in comparison to fertile cases

• 2. . To study the expression of stimulatory receptors of natural killer cell.
• 3-To study the expression of inhibitory receptors of natural killer cell.

Study Overview

• Status: Unknown
• Conditions: Female; Recurrent Miscarriage; Unexplained Pregnancy Loss

Detailed Description

NK-cell functioning is controlled by a wide range of receptors that are expressed on the cell surface. These receptors are either inhibitory or activating in nature. The family of inhibitory receptors consists of the killer immunoglobulin-like receptors (KIR) or Ig-like receptors (CD158), the C type lectin receptors (CD94-NKG2A) and leukocyte inhibitory receptors (LIR1, LAIR-1). Activating receptors are the natural cytotoxic receptors (NKp46, NKp44), C type lectin receptors (NKG2D, CD94-NKG2C), and Ig-like receptors (2B4). A particular NK cell typically expresses two to four inhibitory receptors in addition to an array of activation receptors. The killing by NK cells is mediated through several activating NK receptors. Among these are NKG2D and the three natural cytotoxicity receptors (NCRs), NKp30, NKp44, and NKp46 (Yang et al., 2000) Osne of the natural cytotoxicity receptors (NCRs) NKp46, , is a unique marker that functions in NK cell cytotoxicity and cytokine production. Expression of NKp46 on NK cells is lower in women with recurrent pregnancy loss, so evaluation of NKp46 on peripheral blood NK cells may provide a means of screening for reproductive abnormalities (Fukui et al., 2015).

During pregnancy, decidual NK cells comprise ∼70-80% of the decidual lymphocytes and are considered a special NK subset that does not exert cytolytic functions against trophoblast cells and has generally reduced cytotoxicity (Hanna and Mandelboim, 2007).

These cells express activating NK receptors, including all the NCRs and NKG2D. However, instead of triggering cytotoxicity, these receptors act to stimulate secretion of cytokines and angiogenic factors, which are essential for trophoblast invasion and vascular modifications (Hanna et al., 2006).

One study reported that pNK cell levels show changes in decidual NK cell levels (Park et al., 2010). Whereas some other reports have shown that the assessment of peripheral blood NK cells would not

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 088
    • Yossra Mahmoud Mohammed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

We will recruit patients from outpatient clinics from Assuit University Hospital,Women fulfilling eligibility criteria will be included after careful gynecologycal examination,Those who consent to participate will be referred to the lab for investigation.

Description

Inclusion Criteria:

• 1.Age less than 40 years. 2.History of two or more spontaneous miscarriages .

Exclusion Criteria:

• 1. Age more than 35 years. 2. Women with elevated level of TSH above (2.5 mIU/ml) or prolactin above( 19.5 ng/mL)and uncontrolled DM.

  3. Women with autoimmune disorder (antiphospholipid antibody syndrome)with LA1/LA2 ratio more than( 1.2).

  4.Women receiving oral contraceptive pills.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
unexplained recurrent pregnancy loss; peripheral blood sample examined by flowcytometry
control fertile multipara; peripheral blood sample examined by flowcytometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
asses the number of Natural killer cells	flowcytometry	15 month

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Assiut University, Assiut University

Publications and helpful links

General Publications

• Fukui A, Kamoi M, Funamizu A, Fuchinoue K, Chiba H, Yokota M, Fukuhara R, Mizunuma H. NK cell abnormality and its treatment in women with reproductive failures such as recurrent pregnancy loss, implantation failures, preeclampsia, and pelvic endometriosis. Reprod Med Biol. 2015 Apr 11;14(4):151-157. doi: 10.1007/s12522-015-0207-7. eCollection 2015 Oct.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2019
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): July 20, 2020

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): May 8, 2019
• Last Update Submitted That Met QC Criteria: May 6, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: NK ;natural killer cells
• Additional Relevant MeSH Terms: Pregnancy Complications; Abortion, Spontaneous; Abortion, Habitual
• Other Study ID Numbers: 17200339

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Study Protocol
   Information identifier: IRB17200056

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No