What Testing Can be Done for RPL? #3

The immune system is a very complex system. When an illness occurs and the body's tissues are attacked by its own immune system, this is known as an autoimmune disorder or disease. Some autoimmune issues include systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile diabetes (type 1), etc. All of these issues can contribute to infertility or RPL.

The immune system is another complex system. I will do my best to explain how it works but please check this site out "How Your Immune System Works".

"The immune system is balanced between a Th1 (autoimmune) and Th2 (pregnancy or suppressive) response. Most people have a balanced system. Women with implantation failure or RPL are unbalance. They are too Th1 activated with the autoimmune 'bad guys'."

-Dr. Alan E. Beer

What are Th1 & Th2? Well these are T-helper cells (CD4) or a type or white blood cells (leukocytes) that are produced in the Thymus (hence the T), the gland next to the heart. Th1 cells are responsible for sending a chemical message called lymphokines. This chemical message is sent to B cells (produced in the bone marrow) telling them to make antibodies. Th2 cells are a second type of T-helper cells that act to restrain antibodies. Th2 cells help the body to accept foreign material or cells. In sense, Th1 cells are the "aggressors" cells and the Th2 cells are the "pacifiers" cells. If the Th1 cells become overly aggressive they can attack the wrong targets causing an autoimmune disorder. However, sometimes Th2 is overly suppressing of the Th1 cells and this can leave the body very vulnerable, susceptible not only to infection but tumors as well.

All this talk about antibodies; so what are they? Antibodies are proteins that destroy antigens aka virus, bacteria, fungi or any harmful substance that enters the body. Every antibody belongs to a group of proteins called immunoglobulins (Ig). Attached to the surface of a B cell is an Ig molecule.

Hopefully this is making some sense and you can now see why the Th1:Th2 ratio is so important now. Moving on to what may also accompany an antibody onslaught. An overproduction of proinflammatory cytokines also known as the cells messenger. Cytokines "interact with cells of the immune system in order to regulate the body's response to disease and infection". They also "mediate normal cellular processes in the body".

These messages in between cells then prompts the NK cells, macrophanges, neutophilis and T cells to go in for the kill. Most commonly they will attack connective tissue (tendons, skin, muscles, etc), joints, nerves, thyroid and pancreas. These particular targets cause some commonly known autoimmune diseases including Arthritis, Lupus, Graves' Disease, Crohns Disease, Rheumatoid Arthritis, Guillain-Barre Disease and psorasis.

There is a test called Th1:Th2 Cytokine Assay that simply counts the number of each Th1 & Th2. While searching for normal lab values I came across this journal article Systemic Th1/Th2 cytokine responses to paternal and vaccination antigens in preeclampsia". Interestingly enough it was thought that a "Th1 shift has been suggested to be involved in the pathogenesis of preeclampsia". Hmm...however, apparently this article proved Th1 to be no different. Anyway, I have had poor results in finding a "normal" lab value for Th1:Th2 Cytokine Assay. If anyone has any insight please do not hesitate to comment below.

One other thing I want to review are ANA's or antinuclear antibodies. These are antibodies designed to go attack a cells nucleus. ANA is another test that can be performed with those who have infertility or RPL issues. Just because one ANA is positive does not indicate a cause of infertility or RPL. The presence of one antibody mayindicate other autoimmune issues. ANA's commonly go hand in hand with hyperactive NK cells.

"ANAs are found in 20-30% of women with RPL."

"7% of women who are unable to conceive naturally produce antibodies to sperm."

Two types of antithyroid antibodies (ATA's) exist: antithyroid peroxidase and antithyroglobulin antibodies. ATA's are also linked to a predisposition to other autoimmune disease. One important factor I want to mention is it is important when testing for ATA's that the lab use the test ELISA. If a less sensitive one is used 1 in 5 women who carry ATA's will go undetected. Women with ATA's should also be tested for elevated levels of CD56+ NK cells, CD19+/5+ cells and activated T cells, according to Dr. Beer.

- 30% of women with RPL will test positive for one or both ATA's and are twice as likely to have a m/c then women without ATA'S.

LAC or Lupus Anticoagulant are antibodies against phospholipids that prevent blood clotting in a test tube. The presence of LAC my be responsible for causing tiny blood clots. Lupus antibodies may be present in those with systemic lupus erythematosus (SLE) or without SLE. Due to temporary side effects of an infection, this test should be repeated in 6-8 weeks.

All this talk about Natural Killer Cells (NK Cells). What are they? They are type of white blood cells or lymphocytes responsible for attacking viruses and/or cancer. According to MILab website a NK cell assay, "tests the killing function of circulating NK cells as well as the ability of interleukin-2 (IL2) to stimulate and intravenous immunoglobulin (IVIg) to suppress that activity. NK activity can be measured as a bioassay that determines the ability of activated NK cells to kill their target (K562 cell line)."

- Approximately 40% of patients undergoing IVF who have been diagnosed with endometriosis display increased NK activity.

The following tests are from Dr. Beer's book, with little side comments about each. You can also find some of this information on his website.

CD3 (Pan T cells) - Normal Range: 63-86% - If CD3 is low this is when the immune system is weak. Typically infertile patients or RPL patients often have high normal range values.

CD4 (T-helper cells) - Normal: 31-53% - Again women with fertility problems are typically in the high normal range value. Those who are low could have a serious health problem.

CD8 (T-Cytotoxic Suppressors) - Normal: 17-35% - These cells moderate the activity of Th-1 lymphocytes. In women with RPL/infertility, CD8 is often low.

CD19 (B-Cells) - Normal: 3-8% - Once again usually women with high normal OR elevated percentages are in women with immune-mediated infertility or RPL.

CD56+/CD16+ (Natural Killer Cells) - Normal: 3-12% - Levels are often elevated in women with infertility or RPL, leading to IVF failure, BO, or CP.

CD56+ (Natural Killer Cells) - Normal: 3-12% - These particular NK cells can be turned on by pregnancy & deteriorates the embryo.

CD3/IL-2R+ Cells - Normal: 0-5% - Women who have an autoimmune disease may also have above-average levels.

CD19+/5+ (B-1 Cells) - Normal: 2-10% - These particular cells can produce antibodies to hormones and neurotransmitters.

Are you confused yet? Yes, this is all very overwhelming and can be very confusing! I hope I've simplified some of this information that you aren't confused right now. I remember the first time I read "Is Your Body Baby-Friendly?" I skipped a lot of it because even coming from a medical background the medical jargon intimidated me. Its ok. This is nothing that you need to understand over night.