I. Definition.
1. A class of antibodies produced in vivo that block the biological effect of T cell receptors on the antigen by binding to the corresponding antigen on the cell membrane surface or by binding to the corresponding soluble antigen (e.g. allergen).
2.Some antibodies against tumor antigens can prevent effector cells from recognizing and attacking tumor cells by binding to the corresponding antigens, which facilitates the continued growth of tumor cells.
3. Antibodies produced by maternal exposure to paternal antigens during pregnancy can bind to placental cell surface antigens, thus blocking maternal cytotoxic T cells from launching immune attacks on the embryo and playing a role in protecting the fetus and maintaining pregnancy.
4. In the serum of normal pregnant women, there exists a specific IgG antibody against the spouse’s lymphocytes, which inhibits the lymphocyte response (MLR), closes the cytotoxic effect of maternal lymphocytes on the cultured trophoblast, prevents the recognition of inhibitors of fetal antigens by helper T cells, and blocks the attack of the mother’s immune system on the embryo. Sequestration of homologous antigen-stimulated lymphocytes produces macrophage movement inhibitory factor (MIF), so it is called a confinement antibody.
Types of Containment Antibodies
The main types of confinement antibodies found so far are as follows.
1. Anti-warm B-cell antibodies: anti-fetal B-lymphocyte surface HLA-D/DR antibodies;
2. Anti-cold B-cell antibodies: These are non-HLA cold B antibodies;
3. Anti-specific antibodies: genetic antibodies to HLA-D/DR receptors on the surface of maternal helper T cells;
4.Anti-TLX antibody: an antibody against common antigen of villi and lymphocytes, which can close the mixed lymphocyte reaction;
5, anti-Fc receptor antibodies: non-cellular barrier antibodies that close the Fc receptor on the husband’s B lymphocytes;
6. complement-dependent antibodies against the parent (APCA);
III. Mechanism of action of the blocking antibodies
In vitro studies have shown that the mother can produce sensitized T cells during pregnancy, which can destroy embryonic cells. However, the killing function of sensitized T cells can be inhibited by sexual antibodies, but in about 80%-90% of women with habitual abortion, no such specific closed antibodies are measured and unsuppressed cytotoxic cells exist in the body. These cells can act directly on the embryo or indirectly damage the fetus or placenta by releasing inflammatory mediators, which can lead to miscarriage.
IV. Significance of the test
Modern reproductive immunology considers pregnancy as a successful semi-identical transfer process that protects the mother from foreign microorganisms and maintains the continuation of pregnancy without immune rejection of intrauterine embryo grafts when maternal immune function is normal. Recurrent spontaneous abortion (RSA) occurs for two or more consecutive times and accounts for 0.5% to 3% of the total number of pregnancies. Its pathogenesis is complex, involving genetics, reproductive endocrinology and other etiologies, and the causes are unknown in about 41.18% to 60.00% of cases, 80% of which are related to immune factors.
Blocking antibodies are IgG-type antibodies produced by human leukocyte antigens, trophoblast and lymphocyte cross-reacting antigens (TLX) that stimulate the maternal immune system. Studies have concluded that APLA in the blood of pregnant women can exhibit the following effects.
1, APLA neutralizes alloantigens without rejection of the fetus;
2. The antibody acts directly on immunocompetent cells such as CTL cells, NK cells, etc;
3. Binding directly to the antigens of the target cells, thus reducing their sensitivity to the immune response involving the receptor cells. Previous studies have suggested that the occurrence of recurrent spontaneous abortion is related to maternal APLA deficiency, and the greater the number of miscarriages, the greater the likelihood of APLA deficiency in the patient’s body; insufficient APLA production results in strong maternal rejection of the fetus, which can occur in early pregnancy with recurrent spontaneous abortion, and in late pregnancy with gestational hypertension, intrauterine growth restriction, or even intrauterine fetal death. Therefore, it is necessary to test for APLA in patients with recurrent spontaneous abortions.
HLA is a highly metastatic, tightly linked gene group located on the short arm of human chromosome 6, and is a class of antigens present on the surface of various tissues and nucleated cells that can cause strong rejection reactions. HLA-G is specifically expressed in the trophoblastic layer of the placenta.
Couples with recurrent spontaneous abortions contain the same HLA antigen more frequently than normal couples. The excess of shared antigens prevents maternal recognition of the gestational embryo as an alloantigen and does not stimulate maternal production of APLA sufficient to maintain the pregnancy, and the lack of antibody regulation results in an immune attack by the maternal immune system against the embryo leading to miscarriage. Due to the genetic polymorphism of the HLA gene, the probability of molecular compatibility of HLA antigens on the surface of cell membranes between individuals is low, constituting homozygous immunity.
In normal pregnancy, the HLA antigens of the couple are incompatible and the paternal HLA antigens (on the trophoblast surface) carried by the embryo stimulate the maternal immune system and produce APLA, the specific IgG antibody against the spouse’s lymphocytes (APLA), which inhibits the mixed lymphocyte response and binds to the HLA antigens on the trophoblast surface, overriding the HLA antigens from the parent, thus closing the maternal cytotoxic effect of lymphocytes on trophoblast cells and protects the embryo or fetus from rejection.
Domestic and foreign scholars agree that RSA is caused by the protective response of the mother due to her inability to recognize the paternal antigen. Clinical use of immunotherapy with maternal lymphocytes induces an alloimmune response in the mother, resulting in APLA and microlymphocytotoxic antibodies, making the maternal immune system less susceptible to immune attack on the fetus and allowing the pregnancy to continue.
Some authors believe that RSA is associated with the presence of a maternal-specific abortion susceptibility gene or monomer that may be present within or closely linked to the HLA complex. Maternal bodies containing susceptibility genes or monomers are hyporeactive to embryonic antigens and also fail to produce APLA, exposing the embryo to rejection by the maternal immune system and miscarriage occurs.
Clinical testing for APLA is essential in patients with recurrent spontaneous abortions. For patients who are negative for APLA, active immunotherapy with husband’s lymphocytes can be targeted, because the more miscarriages these patients have, the more serious the disorder of the immune system in their bodies, and without targeted and effective immune interventions, they will hardly have a chance to become mothers.
Since 1981, Taytor and Beer et al. established RSA lymphocyte active immunotherapy, and after more than 20 years of clinical studies, it has been shown that immunotherapy is effective in preventing APLA-deficient RSA. 72.73% to 86.2% of pregnancies have been successfully treated with lymphocyte immunotherapy in patients with recurrent spontaneous abortions of unknown cause by different scholars at home and abroad, and no side effects on mother and child have been found. The rate of positive APLA was significantly higher than that before treatment, and the success rate of re-pregnancy in APLA-positive patients was significantly higher than that in negative patients.