Implantation Dysfunction

Rather it is the activity (toxicity) of NK cells that matters as mentioned. This activity can best be measured using the blood, K-562 target cell test (the gold standard) and/or endometrial biopsy for cytokine activity.

With the K-562 test, the most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In addition to reporting the result of the K-562 test, in the “native state” (without adding, Immunoglobulin-G (IVIG) or Intralipid (IL) which many laboratories erroneously do to try and determine whether either or both of these immune therapies would have a therapeutic benefit or is/are unlikely to be of clinical value. The entire premise upon which this assertion is based, is in my opinion flawed. Clinically such NK cell deactivation can only be significantly affected in vivo as it takes more than a week following infusion to occur. Thus, what happens to the percentage of target cells killed with the K-562 test, by adding IVIG or IL is in my opinion irrelevant. Another way to assess endometrial NKa is by measuring TH-1 and TH-2 cytokines in endometrial tissue derived through biopsy. TH-1 cytokines kill the trophoblast (the root system of the embryo). Thus if is an excess of TH-1 cytokine activity is found with/without a disruption in the TH-1: TH-2 ratio, this points to NK cell activation.

There are basically two causes of immunologic implantation dysfunction (IID), a) Autoimmune (85%), b) Alloimmune (15%). The former occurs when the body reacts to its own tissue and the latter (far less common) when the male and female partners share certain genotypic similarities involving DQ alpha and HLA genes. In both cases IID results in rejection of the pregnancy due to uterine Natural Killer (NK) Cell and T-cell activation leading to the release of an excessive amount of TH-1 cytokines. These, “toxins” attack the embryo’s root system (trophoblast), killing the cells and causing implantation to fail.

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