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.

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

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.