Future directions of clinical laboratory evaluation of pregnancy

Abstract

In recent years, our understanding of how the immune system interacts with the developing fetus and placenta has greatly expanded. There are many laboratories that provide tests for diagnosis of pregnancy outcome in women who have recurrent pregnancy loss (RPL) or pre-eclampsia. These tests are based on the premise that immune response to the fetus is equivalent to the adaptive immune response to a transplant. New understanding leads to the concept that the activated innate response is vital for pregnancy and this can result in more effective testing and treatment to prevent an abnormal pregnancy in the future. We describe here only three such areas for future testing: one area involves sperm and semen and factors necessary for successful fertilization; another area would determine conditions for production of growth factors necessary for implantation in the uterus; finally, the last area would be to determine conditions necessary for the vascularization of the placenta and growing fetus by activated natural killer (NK) cells (combinations of killer cell immunoglobulin-like receptor (KIR) family genes with HLA-C haplotypes) that lead to capability of secreting angiogenic growth factors. These areas are novel but understanding their role in pregnancy can lead to insight into how to maintain and treat pregnancies with complicating factors. Keywords: male factor; preterm labor; recurrent pregnancy loss; seminal plasma; sperm INTRODUCTIONWhen utilizing clinical immunological testing in recurrent pregnancy loss (RPL) or preterm delivery, it should be considered that the primary function of the immune system in pregnancy is angiogenesis and its secondary function is to function as a system to kill and remove foreign pathogens. Alterations in the immune system can affect angiogenesis or the blood flow, which is necessary to maintain placental growth and thereby may divert the immune system from its non-pregnant primary function. At present, the most commonly performed tests to monitor and treat women with RPL are tests for autoantibodies such as antiphospholipid antibodies, antinuclear antibodies and anti-thyroid antibodies.1-3 In addition, assays for lymphocyte subsets and their functions, determination of HLA histocompatibility genes and genes related to thrombophilic conditions are used by some physicians to aid in treatment. Some physicians test women to determine if their RPL are due to an inappropriate inflammatory immune response, which may be treated by anti-inflammatory drug regimens. Some of the tests that are performed have been a matter of controversy but one might consider that women with histories of RPL should be tested to determine if a reason for the repeated miscarriages can be identified. Finally, women with preterm delivery usually are tested for infections or fetal fibronectin which can be helpful in the treatment. 4 The immune system is an endocrine-like system capable of producing numerous peptide hormones (cytokines and chemokines). These hormones are key in the vascularization necessary for pla...

Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface

“…It is still unknown how dNK cells disorder naturally, but it is essential for maintaining the appropriate activation state of NK cells in each normal pregnancy. Therefore, inhibition of NK cells in clinical treatment function may lead to greater risk (Beaman et al, 2014). Some clinical testing found that the number and activity of peripheral blood NK cells have "relevance" to adverse pregnancy; therefore, patients have been given glucocorticoid, intravenous immunoglobulin and anti-TNF-α antibody for treatment (Moffett and Shreeve, 2015).…”

The Role of HLAC and NK Cells in Fetal Growth Restriction

“…A suitable combination will cause activations of NK cells and angiogenesis during placental growth and cause a good pregnancy, if the combination does not proper, it brings difficulty during pregnancy period. 19 Vol 5, No 3 July 2017 HLA-C and NK cells in fetal growth restriction 147…”

Clinical molecular genetics evaluation in women with reproductive failures

“…In contrast to HLA class II antigens, more well‐defined studies have demonstrated the effects of MHC class I interactions with killer cell immunoglobulin‐like receptors (KIR) molecules during pregnancy 11,42,43 . Patients' KIR genetics can be divided into two haplotypes (A and B) whereby each diploid genome will consist of either AA, AB, or BB groups.…”

“…Patients' KIR genetics can be divided into two haplotypes (A and B) whereby each diploid genome will consist of either AA, AB, or BB groups. AB or BB groups are referred to as the Bx genotypes 42,43 . Individuals with the Bx genotypes have more than one gene encoding activating KIRs, such as 2DS1, 2DS2, 2DS3, 2DS5, or 3DS1 43 .…”