New Developments in the Evaluation of Immune Abnormalities in Couples with Recurrent Pregnancy Losses: Infertility and Miscarriages Following one Live-born Child
The information contained in this article is not intended to be a medical diagnosis, treatment or medical advice in any way, as it is general information and cannot be relied on without consultation with your physician. It is not intended nor is it implied to be a substitute for profession medical advice. As medical information can change rapidly, we strongly encourage you to discuss all health matters and concerns with your physician before embarking on new diagnostic or treatment strategies.
Couples with one live born child who subsequently experience loss of all
pregnancies through secondary abortions are an enigma to their physicians
and often receive advice that prevents them from receiving a complete evaluation.For couples in this category it is easy for the physician to minimize the problem by saying, "Just keep on trying, it worked once for you, it will probably work again." If physicians applied this same advice for couples with the Rh problem, where a first Rh incompatible pregnancy initiates an immune problem in the mother and subsequent pregnancies makes the problem worse, they would be accused of poor counseling tactics. Present studies of couples with secondary miscarriages suggest that this problem is not dissimilar to the Rh problem. It appears to involve an immune response in the mother that is initiated by a fetus with a specific white blood cell type.
Every person's white blood cell type (Tissue Type, HLA Type) consists
of 10 numbers, half of which come from each parent. These white blood cell
numbers are molecules (antennae) that are present on the surface of the
person's white blood cells. and they serve important functions in recognizing foreign interlopers (germs and viruses) that enter our body. This recognition event results in an immunity response that eventually leads to the death of the germ or virus and the formation of an antibody against the germ or virus that prevents recurrence of the disease. Red blood cells also have molecules (antennae) that allow the testing lab to know if the person is a blood group A, B, or O and whether the blood cell is Rh positive or negative.
A representative white blood cell type is as follows: A1, A12; B7, B12;
C4, C2; DR3, DR8; and DQ4, DQ1. One number at each locus (A, B, C, DR and DQ) comes from the mother, the other from the father. Research in our laboratory since the last newsletter has used molecular genetics technology (DNA testing) of mothers, fathers, live born babies and babies that miscarry again despite the best therapy we know how to offer has led to a breakthrough in our understanding of this problem. Mothers and fathers who share the DQ white blood cell numbers and produce a baby with numbers the same as the mother, miscarry this compatible baby far more frequently than when these numbers differ between mother and father. These pregnancies fail even too early for tissue to pass, even before chromosomal analysis of the baby is possible. Unlike the Rh problem where incompatibility (differences in Rh type) between mother and father cause the problem, white blood cell compatibility with the DQ numbers is an unlucky combination.
Couples with secondary abortions (one living child and then spontaneous
miscarriages) are a distinct group. Sixty percent of the first born children of secondary aborting couples are DQ 0501, DQ 0501 (formally called DQ 4.1 homozygous). This means that they are purebred with regard to this part of their white blood cell type. Both mother and dad contributed the same 4.1 gene. An analysis of several hundred live born children who were born following immunologic treatment of their mothers revealed no live born DQ 0501/0501 babies. The following figure graphs the data.
Women whose first baby is DQ 0501, DQ 0501 are at high risk to make an autoimmunity
response that involves the production of an antibody (immunity) in their
body that attacks the glue (Phospholipids) that are important in building
the placenta of the baby. They are also prone to increase the numbers of
Natural Killer Cells in their blood from 4% to over 20-30%. Natural Killer
Cells are a special kind of lymphocyte (white blood cell) that function
in our body to rid us of cancer cells. Each specific lymphocyte population, including the Natural Killer Cells, can be accurately measured in the blood of any person by means of a special technology called flow cytometry, and the changes in the percentages of cells following treatment can be measured with repeated testing.
We know much about the functions of Natural Killer Cells in other situations such as children who need a bone marrow graft from a related family member. In this situation the bone marrow is compatible (a very good match) in that all the DR and DQ numbers of the donor and the recipient match. The child receiving the bone marrow often begins to reject this compatible graft and the white blood cells that do the rejecting are the Natural Killer Cells.
Studies in the laboratory show that this type of Natural Killer Cells
in women with recurrent miscarriage can also damage the early cells of
the baby that will make the placenta. When this situation exists the mother needs special treatment called intravenous gamma globulin, a purified gamma globulin antibody that decreases the toxic activities of these Natural Killer Cells. Prednisone which is a steroid used commonly during pregnancy in women with immune abnormalities does not effectively treat this problem.
Intravenous immunoglobulin (lVIg) is a powerful and safe tool to modulate abnormal responses of the immune system. The availability of an effective and safe preparation of gamma globulin (IVIg) for intravenous use was only possible by the end of the 1970's. At the beginning its therapeutic application in patients with immune deficiencies was not clear. Soon it became evident that it could be an effective treatment for many autoimmune conditions. A growing body of data in this regard exists and intravenous immunoglobulin is now widely used as a means to safely modulate the immune system in patients with autoimmune disorders.
Couples with recurrent pregnancy losses and particularly couples with
one living child who subsequently miscarry all fetuses are recommended
to receive testing to determine their DQ white blood cell numbers by molecular genetic techniques. The woman should also have her Natural Killer cell numbers and function tested.
Dr. Alan E. Beer has presented this new information at National Medical
Conferences and at International Conferences in Australia, Greece, Europe and South America.
Alan E. Beer Center for Reproductive Immunology & Genetics
15151 National Ave. #2; Los Gatos, CA 95032; Phone: (408) 356-9500; Fax: (408) 356-9509; E-mail: info@repro-med.net.
Date: 8-28-08, Time: 3:48 pm.
General Question? E-mail: info@repro-med.net.
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