Overview of habitual abortion due to blocking antibody deficiency

As we all know, habitual abortion has a great harm to women's physical and mental health. Although there are many reasons for habitual abortion, clinically about 40% to 80% of patients with habitual abortion have unknown causes. For habitual abortion of unknown causes, scholars have conducted research on blocking antibody deficiency habitual abortion, and have made certain progress in the research. The following is an introduction to the overview of blocking antibody deficiency habitual abortion.

Unexplained habitual abortion (UHA) is related to immune factors, which can be divided into two types: autoimmune and alloimmune. The lack of blocking antibodies (BA) belongs to the alloimmune type and is one of the important causes of UHA. Clinical practice has confirmed that active immunotherapy for UHA is a safe and effective treatment method with a high success rate.

1. Mechanism of active immunotherapy

In normal pregnancy, paternal antigens carried by trophoblasts can stimulate the maternal immune system to produce a class of IgG antibodies, also known as BA, which can combine with maternal lymphocytes and embryonic trophoblasts, thereby blocking antigen recognition between mother and child and the secondary rejection reaction caused by it. Therefore, lymphocytes extracted from the husband's peripheral blood are currently used clinically to stimulate patients with recurrent miscarriage to increase BA levels in the body, induce CD8 cell proliferation, and produce immune tolerance, thereby improving the chances of successful pregnancy in patients with recurrent miscarriage. The exact mechanism of immunotherapy has not yet been fully clarified. Most researchers believe that BA can prevent the paternal antigens of the embryo from being recognized and killed by the maternal immune system by binding to fetal placental trophoblast antigens or binding to maternal lymphocytes. During pregnancy, the embryonic trophoblast is the part that the fetus is in direct contact with the mother. The trophoblast expresses a large number of trophoblast membrane antigens (TA), which are divided into TA1 and TA2. TA1 induces CD8 to produce cytotoxic lymphocyte responses, inhibiting embryo implantation and trophoblast growth. TA2 is the trophoblast cell (T) paternal lymphocyte (L) cross (X) antigen (TLX antigen), which stimulates the mother to produce BA, mainly mediating the production of anti-TLX antibodies, and combines with the TLX antigen on the surface of the trophoblast cells to form a protective effect, protecting the fetus and placenta from the attack of maternal immune cells, and has an immunotrophic effect that is beneficial to pregnancy. When the mother cannot produce blocking antibodies, lymphocytes inconsistent with the mother's TLX (such as the husband's lymphocytes) can be injected to produce BA, which has the effect of promoting the release of PGFs and inhibiting the toxicity of NK cells, showing an anti-abortion effect.

2 Active immunotherapy

2.1 Scope of application: 3 or more consecutive spontaneous abortions, excluding other pathogenic factors (including chromosomal abnormalities of the couple, reproductive tract malformations, endocrine abnormalities and male factors, etc.), and negative blocking antibodies.

2.2 Treatment methods: ① intradermal injection of lymphocytes for immunization, ② intravenous injection of concentrated white blood cells, ③ small-volume whole blood transfusion. The above methods are relatively easy to collect blood from the husband, with a low incidence of cross-infection, and the wife feels mentally safe after injecting the husband's blood. Therefore, most research institutes focus on immunization with the husband's lymphocytes. If unrelated healthy individuals' blood is used for immunotherapy, ABO blood type matching is required, and attention should be paid to transfusion reactions during treatment. Immunization can be done before or after pregnancy. Most research institutes often conduct immunotherapy before pregnancy, with an interval of 3 to 4 weeks each time, and 3 times as a course of treatment, and then guide conception. If conception is not achieved, continue to immunize once every 3 to 4 weeks, and continue immunization within 3 months after pregnancy.

2.3 Injection method: Draw blood from the husband's cubital vein, separate lymphocytes under sterile conditions, adjust the concentration to an appropriate amount, with a cell count of 20×105/ml to 40×105/mL[1], and inject subcutaneously into the inner forearm of the patient at multiple points, once every 3 to 4 weeks, 0.3 to 0.5 ml/time.

2.4 Clinical manifestations: After active immunization, patients experience symptoms such as redness and itching on local skin, most of which disappear within 3 to 5 days. As the number of treatments increases, the symptoms gradually ease.

3. Efficacy evaluation

Clinical studies have shown that the pregnancy success rate of lymphocyte immunotherapy is 70.00% to 94.12%. However, different centers and scholars have different views on whether blocking antibodies are produced after immunotherapy and whether there is a correlation between pregnancy outcomes. Pandey et al. believe that whether blocking antibodies are produced after immunotherapy can be used as an important factor in judging pregnancy outcomes. However, Hao Guiqin et al. believe that whether blocking antibodies turn positive after active immunotherapy has no correlation with pregnancy outcomes. Agrawal and Tamura's study showed that the mixed lymphocyte reaction blocking factor (MLRBF) of patients after active immunotherapy increased significantly, which can be used as an indicator of the efficacy of UHA patients. Check[6] studied the changes in progesterone-induced blocking factor (PIBF) in UHA patients before and after active immunotherapy and believed that PIBF increased significantly after immunotherapy.

4 Adverse reactions

Adverse effects of active immunotherapy: Malinowski et al. found that the intrauterine development of the fetus during pregnancy, growth after birth, and mental activity status of the lymphocyte immunotherapy group and the control group were basically the same as the average level of normal children, with no significant difference. Therefore, it is believed that lymphocyte immunotherapy is relatively safe for fetal development and growth. Transfusion reactions, allergic reactions, and the risk of infection with viruses and infectious diseases may occur during immunotherapy. Severe complications may worsen the risk of the mother's potential autoimmune system. Tanaka et al. reported a fetus with thrombocytopenia born by a lymphocyte immunotherapy patient. The cause may be that active immunization induced enhanced anti-HLAIgG levels in the mother's blood, and HLAIgG antibodies entered the fetus through the placenta. No other malformed or low-weight babies have been found to be born after immunotherapy, and no case of treatment affecting the mother has occurred.

5 Treatment status

Pregnancy is a successful semi-homologous transplantation process. When the mother's immune function is normal, it not only protects the mother from invasion by foreign microorganisms, but also prevents immune rejection of the intrauterine embryo transplant and maintains the continuation of pregnancy. The embryo will only be accepted and the pregnancy can be maintained if it is recognized by the mother's immune mechanism.