Neonatal Umbilical Cord IgE Tests: Rationale for Their
Use in Screening Infants for Impaired Immunity and
Increased Vulnerability to Childhood Vaccines

Serum IgE: Its Physiology and Biological Effects

There are four major categories of immunoglobulins in the human system: 1) the IgG fraction, or gamma globulins, which carry long-term immunity, 2) the IgM fraction, or macroglobulins, which provide immediate but nonspecific protection with acute infections, 3) the Secretory IgA of the mucous membranes, sometimes referred to as "antiseptic paint," and 4) the IgE system. All immunoglobulins are produced by lymphocytes located in the bone marrow, a class known as B-lymphocytes. Some texts speculate that the IgE antibody system originally evolved as a protection against intestinal parasites. Elevated levels of IgE antibodies are found in patients with parasitic infestation and atopic/hypersensitivity diseases such as asthma, eczema, and hay fever, but they do not seem to be related to autoimmune conditions. In some children with atopic diseases plasma IgE antibodies may be elevated 5 to 20 times normal. The IgE molecule has a high-affinity for the surface membranes of mast cells and basophils, and once exposed to or cross-linked with allergenic antigens, such as pollen or mold, pro-inflammatory lipid-derived mediators are released which may produce immediate hypersensitivity reactions with vascular leakage, tissue swelling, inflammation, and/or broncho-constriction.

During fetal life lymphocytes produce very little immunoglobulins under ordinary circumstances, presumably due to the protected environment in the uterus (although the fetus can produce IgM and IgA when there have been prenatal infections). For this reason the IgG levels in the term infant are similar to maternal levels as a result of transplacental transfer. However, no other class of immunoglobulin passes the placental barrier, including IgE, so that these are usually absent in the newborn infant.

It is important to add that with breast feeding there is some transfer of antibodies from the mother, especially IgA, lysozyme, and lactoferrin, along with large numbers of lymphocytes and monocytes during the first two months following birth to provide protection while the baby's own immune system is slowly maturing, a process requiring a number of years. (1)

Rationale for Use of Neonatal Umbilical Cord IgE as a Screening Test

Very few today would question that we are dealing with an increasing pattern of sickness in today's children as compared with earlier generations. Neurobehavioral problems are epidemic including autism, learning disabilities, and attention deficit hyperactivity disorder. If you doubt this, ask any experienced elementary school teacher who has been teaching for a number of years. In my experience, and I have talked with many of them, their answers have been unanimous and emphatic that they are now seeing a much greater incidence of these disorders with visible increases almost by the year. The same can be said for allergic disorders and general patterns of sickness.

Until recently some have contended that the increase in these disorders has been due to better diagnosis, but this is no longer the case as reflected by current CDC (Center for Disease Control) statistics. What then are the causes of this ominous health trend in our children? There are clues which relate in part to vaccines. Epidemiologic studies from England, (2) Sweden, (3) Africa, (4) and New Zealand (5) have consistently shown a much greater incidence of atopic disorders in fully vaccinated children as compared to those with limited or no vaccines.

F Imani and KE Kehoe, in following up on a study showing that the measles virus infections (synergizing with Interleukin-4) cause an IgE class switching of B-Lymphocytes, found the same switching from the MMR vaccine leading to an increase in the expression of IgE (and by inference away from the protective IgG and IgM antibodies. (6)

There is a relatively rare condition known as the "hyperimmunoglobulin E syndrome" (HIE) which could serve as a model. HIE syndrome is characterized by high IgE serum levels, chronic dermatitis, and recurrent bacterial infections with Staphylococcus aureus and other Polysaccharide encapsulated organisms. The proposed mechanism arises from insufficient suppressor T cells, which is manifested in part by reduced production of interferon (IFN)-alpha and tumor necrosis factor. (7) For our purpose here it is important to point out that the same abnormal antibody responses have been documented in some patients in response to vaccines. (8) In addition, studies of children with HIE by Leung et al at the Children's Hospital of Boston found significantly impaired antibody response to recurrent Staphylococcal infections and to Haemophilus influenzae vaccine.(9) (As an explanation for this impaired antibody response demonstrated in the Leung study, it is reasonable to assume that a shunting of the genetic antibody production towards increased pro-inflammatory IgE would be accompanied by a shunting away from the protective IgG and IgM antibodies, although this has yet to be demonstrated in the laboratory).

In brief summary of the above, we have the model of the Hyperimmunoglobulin E Syndrome in which impaired immune response to both bacterial infections and vaccines have been documented. We know that maternal IgG is the only class of antibodies that passes to the fetus through the placental membranes, but that fetuses have been known to generate their own IgM and IgA with prenatal infections. Although apparently IgE has not been found in newborns to date, according to references that I have seen, are there situations arising today in which a fetus may be stimulated to produce its own IgE? I believe that there are.

Most children today are third generation vaccine recipients. Mention has been made above of marked increases in allergic disorders in fully vaccinated children as compared to those with limited or no vaccines, a process that may well be compounded from one generation to the next. At some point this increased proneness to IgE-related hypersensitivity may be communicated to the fetus. Should we not be finding out?

Gross Deficiencies in Safety Testing of Childhood Vaccines and Their Consequences

There are at present growing public and professional concerns about the safety of currently mandated childhood vaccines, as reflected by a series of annual Congressional hearings in Washington DC that have taken place since 1999 dealing with issues of vaccine safety. Sponsored by U.S. House Government Reform Committee under the chairmanship of Congressman Dan Burton, from these hearings there has emerged a consistent pattern of deficiencies in basic science of safety testing of vaccines. As a result of these deficiencies large numbers of adverse reactions may be taking place unrecognized as to their nature, especially delayed-type reactions.

Based on these hearings, scientific evidence does not support the safety of immunizations in that pre-licensing safety surveillance periods on vaccines have been limited to short periods only: days to several weeks. There have been no long-term (months or years) safety studies on any childhood vaccine in use today. In addition, there have been no systematic before-and-after studies on the effects of vaccines on the neurologic, immunologic, or other systems of the body, studies which ordinarily are considered indispensable in forming a foundation of basic science of medical interventions.

Although numerous examples could be provided, perhaps the most flagrant example is that of thimerosal, the mercurial additive, which has been used in vaccines since the 1930s. As we now know, prior to June, 1999 when pharmaceuticals began removing thimerosal from vaccines, some babies received as much as 50 or 75 times the allowed safe dose of mercury in a given day, depending on the combinations of vaccines, according to current US Environmental Protection Agency (EPA) standards. It was only after this issue was raised in the Congressional hearings, with subsequent outrages expressed by some, that the pharmaceuticals began in earnest to remove thimerosal from the vaccines.

In addressing this issue on June 20, 2002, Congressman Burton made the following comment:

"(Do) you mean to tell me that since 1929 we have been using thimerosal, and the only test that you know of was done in 1929, and every one of those people had meningitis, and they all died?"

Congressman Burton went on to state that there could be criminal penalties for any government agency that knew about the dangers of thimerosal and did nothing to protect the children.

Conclusions

To the best of my knowledge, most meaningful safety research for childhood vaccines to date has been privately funded, government agencies having largely failed to provide for this need. The same is true for the present proposed study of neonatal cord blood IgE tests, also privately funded. Aside from its inherent scientific attraction of exploring a relatively new and unknown area, as far as I am aware it will have the distinction of being the first test specifically designed to screen for infants with increased vulnerability to adverse vaccine reactions. It is a precedent that is long overdue.

Harold E Buttram, MD

January 5, 2003

References

(1) Information on physiology of IgE antibodies was found in Williams Text of Hematology, Sixth Edition, Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U (Editors), McGraw-Hill Publ., New York, 2001; Nelson Textbook of Pediatrics, Sixteenth Edition, Behrman RE, Kliegman, RM, Jenson HB (Editors), WB Saunders Co, Philadelphia, 2000; Immuno-Biology; the Immune System in Health and Disease, Fourth Edition, Janeway CA, Travers P, Walport M, Capra JD (Editors), Garland Publ, New York, 1999.
 

(2) Odent MR, Pertussis vaccine and asthma; is there a link? JAMA, 1994; 271:229-231.
 

(3) Alm JS et al, Atopy in children of families with anthroposophic lifestyle, Lancet,
May 1, 1999; 353:1485-1488.
 

(4) Shaneen SO et al, Measles and atopy in Guinea-Bissau, Lancet, June 19, 1996; 347:1792-1796.
 

(5) Kemp T et al, Is infant immunization a risk factor for childhood asthma or allergy?, Epidemiology, November, 1997; 8(6):678-680.
 

(6) Imani F, Kehoe KE, Infection of human B lymphocytes with MMR vaccine induces IgE class switching, Clinical Immunology, Sept., 2001; 100(3):355-361.
 

(7) See reference (1), pages 842-843.
 

(8) Sheerin KA, Buckley RH, Antibody responses to protein, polysaccharide, and pili X174 antigens in the hyperimmunoglobulin E (hyper IgE) syndrome, J Allergy Clin Immunol, 1991; 87:803.
 

(9) Leung DY, Ambrosino DM, Arbeit RD et al, Impaired antibody responses in the hyperimmunoglobulin E syndrome, J Allergy Clin Immunol, June, 1988; 81(6): 1082-7.

RESEARCH
 

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