The immunoreactive theory of selective male affliction.

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The idea the general male preponderance of affliction could be caused by maternal antibodies to male fetuses was first fully articulated by Thomas Gualtieri and Robert Hicks in 1985.   Stated in simpler language,  the immunoreactive model proposes that some male fetuses come to be considered by the mother’s body to be undesireable parasites and get attacked and damaged by the mother’s immune system.  There are three major empirical arguments (sets of facts) in support of this general model.   1) X-linked disorders are insufficiently frequent to fully explain the greater male risk for developmental disorders:  many male-prevalent disorders are known not to be X-linked.  2) Whereas developmental disorders seem to be more often purely genetic in females,  they seem to depend more on gene-environment interactions in males:  complications of pregnancy affect males more than they do females and expression of the various disorders is more heterogenous (variable) in males.   3)  Disorders which affect males more frequently clearly tend to be congenital,  their onset is earlier:  a uterine influence can justifiably be suspected.   

The immunoreactive model proposes that maleness is a complication of the basic (female) prototype,   making maleness a riskier trajectory:  more things can go wrong.   And as I articulate in chapter 6,   this is clearly reflected even in mortality rates.   What then is the main immunological argument in support of the model ?   Gualtieri and Hicks proposed that because maternal parity (number of previous offspring) increases risk for congenital disorders,  this suggests a sort of «memory»,  or sensitization, which the immune system is known to be capable of.  In other words,  the mother could develop a sort of «allergy» to her own male fetuses.  This is a nearly gratuitous argument.  After all,  parity, correlated with aging,  are each known to cause a reduction of endocrinological « competence » of the mother,   and both could affect her reproductive competence in many other non-immunological ways as well.   But there are other indirect arguments in favor of immune mother-son toxicity:   1) male-to-male and female-to-female tissue grafts are less rejected than male-to-female or female-to-male; 2) the mother seems to develop an auto immune disorder (toxemia) more often when the fetus is male;  3) women with repeated miscarriages reject tissue grafts from their husbands more than from third parties.      Maternal immune rejection of the male fetus should probably not be evoked as a major source of sex segregation of pathology,  and probably has nothing to do with most pathologies.   However,  it may well have something to do with a few specific pathologies.   The likeliest candidate,  as far as I can tell, would be autism.    Indeed,  the risk for autism seems seems to depend,  more than the other sex-segregated disorders,  upon sex ratios of the mothers previous offspring.