Might "blood groups" be contributing to pathogenesis in some cases of
autism? At least one author (1a) has suggested why A+ may be a
susceptibility factor, and results of several informal polls among parents
of one or more children with autism are consisent with the idea that the
blood group A+ is over-represented in children with autism (eg, 1b).
Although derived from very preliminary anecdotal information, the
possibility of blood-groups as a possible etiological factor in autism
prompts a question:
By what mechanisms might blood-groups and/or
maternal/paternal/conceptus blood-group differences
participate in neurological damage later manifesting as traits
diagnosed as within the autistic spectrum?
This question's possible answers are diverse and complex. A preliminary
list includes but is not limited to:
1. Some blood-groups are associated with certain infectious agents
known to be capable of affecting the CNS and/or the gastrointestinal
system (gi problems are commonly reported by parents in autism;1c)
2. The most commonly known blood groups are like a tip of the iceberg, ie,
we have numerous cell-surface molecules capable of serving as antigens
that induce immunological responses. Most mothers, fathers, and children
are never tested for blood-group antigens other than the most primary --
eg, A,B,O, and Rh, and perhaps a few others on rare occasions.
3. Hemolytic processes are known to be capable of inducing CNS damage;
hemolytic disease of the newborn (HDN) is often derived from differences
between maternal and concepts blood-groups; and HDN is described by some
authors as occurring, in some infants, with a subclinical, not usually
noticed, presentation.
4. Whether a person is a Secretor or non-secretor may be important,
because of differing infection rates between the two groups.
5. Kell blood-group antigens (the Kell glycoprotein) has sequence
similarity to "mammalian endopeptidases, which process and inactivate
various peptide hormones, such as enkephalins, oxytocin, bradykinin,
angiotensins I and II, substance P, and neurotensin...". (2) This suggests
the potential for CNS-related autoimmune molecular-mimicry processes
to arise if something such as maternal/paternal Kell antigens are
sufficiently different and stimulated.
6. Complement 4 polymorphisms are part of the Chido/Rodgers blood group
system (3); and complement 4b null-alleles and/or reduced levels of 4b
are associated with autism and other CNS-related disorders (eg, 4).
We ought keep in mind that blood-group antigens or maternal/conceptus
differences in blood-group antigens probably are not primary causes in
most cases of autism. However, as better autism studies have shown (5-7),
there are strong associations between autism and the number of certain
adverse-events during the pre-, peri-, and neonatal periods; and many of
these "adverse-events" are highly associated with infectious processes,
which can stimulate immune processes in the mother and/or in the fetus
(8-9).
If an autism/blood-groups study is enacted, using only primary blood-group
categories ought at best lead to soft associations and the oft-repeated
pro-funding phrase, more studies are needed. Contrastingly, a thorough
study of autism/blood-group relationships might look at more than just the
primary blood groups; and perusing blood-groups of mother, father, and
child would provide the most information.
HDN autopsies show extensive brain damage. If an infant does not die from
HDN and therefore has only a "mild" variant, he or she is not likely to
have been autopsied, thus "mild" HDN damage is not likely to be noticed.
I have cross-posted this to several medical and/or neuro listserves
because there are a number of possible mechanisms by which blood-group
and/or maternal/conceptus blood-group differences might serve as
contributing causal-factors in the etiologies in a goodly portion of kids
with autism and autism-spectrum disorders.
Comments and suggestions will be appreciated, either sent me directly or
posted, as you feel appropriate. Thank you.
Teresa
Teresa.Binstock at uchsc.edu
Teresa Binstock <imi2dnvr at amnix.com>
(1a) Peter D'Adamo; see www.dadamo.com.
(1b) Todd Moody, via autism and autism-physio listservs of St. Johns U.
(1c) Numerous postings on bit.listserv.autism; DAN! protocol book via
www.autism.com/ari; Acta Paed 85.9.1076-89 1996.
(2) Frattali AL et al. Human blood group antigens and antibodies. Ch 8 in:
Principles of transfusion medicine. 2nd ed. Rossie EC et al editors.
Williams & Wilkins 1996.
(3) Avent ND. Human erythrocyte antigen expression: its molecular bases.
Br J Biomed Sci 54.16-37 1997. [an excellent review]
(4) eg, Mol Chem Neuropathology. 28.77-81 1996; Neuropsychobiology.
31.53-7 1995; Arch Ped Adol Med 148.180-3 1994; Clin Exp Immunol
83.438-40 1991.
(5) Gillberg C, Gillberg IC. J Autism Dev Disorders 13.2.153-66 1983.
(6) Bryson SE et al. J Am Acad Child Adolesc Psychi 27.418-22 1988.
(7) Piven et al. J Am Acad Child Adolesc Psychi 32.6.1256-63 1993.
(8) Berry SM et al. Am J Ob Gyn 167.895-900 1992.
(9) Sampson JE et al. Am J Ob Gyn 176.77-81 1997.
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