Immunology
The presence of a group of viruses was found to be the main cause of growth of specific toxic cells in the blood known as NK cells (Νatural Κiller cells).
Reproductive Immunology
More specifically, the presence of a group of viruses (namely herpes viruses, including herpes simplex virus) was found to be the main cause of growth of specific toxic cells in the blood known as NK cells or Natural Killer cells or Natural Killers. These are known cells whose concentration is increased in the blood of women with a history of infertility of unknown etiology; their quantitative assessment is the first priority in the investigation of the infertile couple by examination of the Peripheral Blood Lymphocyte Immunophenotype. A very large percentage (~35%) of women with fertility problems show an increase in NK cells in the blood (see a study by our Locus Medicus Center published in the scientific journal Fertility and Sterility, Michou et al., September 2003). It seems that in most cases the increase is due to a subclinical response to herpes viruses in these women. When our research team noticed the involvement of viruses in infertility, a great number of couples with this type of problem achieved their goal after a very simple antiviral treatment. The success mainly concerned cases where the NKs in the peripheral blood were at abnormal levels, but in a relatively small deviation from the upper normal limits. In contrast, when the deviation from normal was greater, then the Lymphocyte Vaccine, which Locus Medicus implements since 1998, is undoubtedly the most reliable treatment according to our experience.
To date, the methods used to detect the presence of viruses do not appear to be at all sensitive. However, with the use of molecular (DNA) techniques, it is revealed that viruses exist in us at a much higher frequency than the one estimated by scientists.
In cases of first trimester miscarriages, the histological picture of the scraping material (carrietage) is characterized by the presence of cytotoxic NK lymphocytes (CD16+) in a diffuse manner and with tropism to the points of contact with the embryonic cells. More specifically, these cells surround necrotic areas of the perishable (pregnant endometrium), which normally include abundant, dispersed embryonic cells. We see no other reason than that the necrosis occurred exactly where the NK lymphocytes met and exerted toxicity on the fetal cells, which – according to the rules of immunology – are ideal targets for the action of NK.
Interestingly, such images, i.e. with the coexistence of NK cells, embryonic cells and necrosis, can also be observed in cases where the concentration of NKs in the peripheral blood is normal. This was our main motive to consider that the fetus could carry viral antigens in it.
Over time, our research team is concerned with the possible presence of similar viruses in sperm as well. The predicted result of such a presence after a vertical transmission of viruses to the fetus, would be:
a) the inability of the fetus to properly multiply
b) the rejection of the infected fetus by the female defense mechanisms.
c) the creation of functional problems of the fetus that can be seen in the late stages of pregnancy.
The content of sperm in microorganisms has not been of concern to the medical sector worldwide. In our view, the purity of the genetic material of the first cell of the fetus is of paramount importance.
The presence of intracellular pathogens and viruses such as HSV 1/2 and CMV in sperm cells can lead to their vertical transmission from the sperm to the first cell of the embryo during fertilization. The presence of viral DNA among the embryonic genome can lead to the expression of viral antigens by the embryonic cells. This causes the NK lymphocytes to manifest tropism against them, resulting in the immunological rejection of the fetus. Remember that the target cells are those whose function is to develop mechanisms of stealing oxygen from the vessels of the endometrium. These cells, called intermediate trophoblast cells, are the ones that produce chorionic gonadotropin (β–hCG). This can result in premature miscarriages, which are misinterpreted as inability to conceive when they occur before the confirmation of pregnancy by hormonal chorionic gonadotropin; or it can even manifest with recurrent miscarriages of immunological etiology.
Even in cases that the fetus survives a vertical transmission of viruses, there is a possibility that the viruses will be considered as “self” by the new organism and will not be treated for the rest of its life. As a result, the fetus will be tolerant towards these pathogens and will therefore coexist with them in the future with unpredictable consequences.
To prevent and avoid the above situation, we recommend the SPI™ TEST (sperm pathogen immunophenotyping test), a new, patented, award–winning diagnostic test that allows for the first time the detection of intracellular pathogens, such as viruses (eg CMV, HSV 1/2) and Chlamydia, inside the sperm, using flow cytometry.
The SPI™ test helps scientists to investigate the etiological causes of male infertility, as the latter may be involved in the immunological causes of premature miscarriage and recurrent miscarriages due to sperm–derived pathogens, even in cases of chronic, subclinical infections, where conventional methods like cultures, immunofluorescence and PCR fail to detect them. It is the most sensitive, commercially available test (more sensitive than standard PCR–based detection methods), while providing excellent specificity, allowing the correlation between infection and infected cell type.
In conclusion, we consider that the immunological etiology consists of two parts: the first part concerns the aggression of the woman against fetal antigens (most likely viral) and is investigated by the immunophenotype, whereas the other one concerns the content of sperm (and therefore the content of the fetus) in antigens, that are mainly identified by the SPI immunological examination.