Reproductive Immunophenotype

Immune cells circulate in our blood system and defend our bodies from attack by invading pathogens, but also from cells within our bodies that have become infected or cancerous.
Sometimes an immune system can be too vigilant and attack it’s own healthy cells, leading to autoimmune diseases. It can also recognise a growing embryo and placenta as being genetically different and target these for elimination. An overactive immune system with elevated levels of immune cells can cause infertility, IVF failure and Recurrent Pregnancy Loss (RPL).

Reproductive Immunophenotype testing looks at the balance of immune cells in the blood. It checks to see if certain types of immune cells associated with infertility/RPL are elevated.
Immune cells look very similar but have different protein markers on their surface called CD molecules (Cluster of Differentiation). To distinguish between different CD molecules/immune cells, an instrument called a flow cytometer (cell sorter) is used. By testing the levels and ratios of different immune cells, it’s possible to check if there is an immunological imbalance and decide the most effective course of treatment for these patients. Some of the more relevant immune cells included in Reproductive Immunophenotype testing are described below.

CD3 (Pan T-Cells)
The CD3 molecule is found on the surface of all mature T-cells. These cells play a central role in immunity. When the CD3 marker is low it indicates a weakened immune system. Normal levels indicate a normal functioning immune system, while higher levels can indicate an overactive immune system associated with infertility/RPL.

CD4 (T-helper Cells)
T-helper cells (Th cells) are a type of T cell that do not directly destroy tumours or pathogenic cells, but instead help the immune system by activating and directing other immune cells. They can direct different immune responses depending on the cytokine messenger they produce. Cytokine messengers are regulatory proteins that will either initiate a pro-inflammatory response (Th1) or anti-inflammatory response (Th2). Read more.. →
Elevated CD4 levels are associated with infertility/RPL.

CD8 (Cytotoxic/Suppressor T-Cells)
CD8 T-cells are the effectors of the immune response. They respond to CD4 and CD3 cells to eliminate infected and abnormal cells. Lower levels of these cells are associated with infertility/RPL as they can become depleted by an overactive immune system.

CD4+/CD25+ (Regulatory T-Cells)
Regulatory T-cells, previously called Suppressor T-cells, can suppress the immune response of other cells. They can stop the immune response once a pathogen or abnormal cell has been eliminated and also play a role in preventing autoimmunity by discriminating between ‘self’ and ‘non-self’. When Regulatory T-cells levels are affected this can result in infertility/RPL.

CD16+/CD56+ (Natural Killer (NK) Cells)
NK cells are a type of immune cell involved in the early detection and elimination of virus infected cells, cells of foreign origin and cancer cells. They are called 'Natural Killer' cells because they can identify and eliminate abnormal cells directly, making them an important first line of immune defence. Read more.. →
NK cell levels elevated above 12% are associated with infertility/RPL.

CD3+/CD56+ (Natural Killer T (NKT) Cells)
NKT cells share properties of both NK cells and T-cells. They can produce large quantities of cytokines rapidly.
Elevated NKT cell levels associated with infertility/RPL.

CD19 (B Cells)
B cells are a type of immune cell that produce antibodies. These antibodies recognise foreign or toxic material and target them for elimination.
B cell levels elevated above 12% are associated with infertility/RPL.

CD19+/5+ (B-1 Cells)
B-1 cells can produce autoantibodies to hormones such as estradiol, progesterone, hCG etc. This can interfere with hormone levels leading to luteal phase deficiencies and poor ovarian response to fertility drugs.
B-1 cell levels elevated above 10% are associated with infertility/RPL.

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