From "Folate Receptor Alpha Autoantibodies in Autism Spectrum Disorders: Diagnosis, Treatment and Prevention" (2021):

Comparison of the Childhood Autism Rating Scale (CARS) after 2 years of treatment (folinic acid supplementation and correction of abnormal nutrient values) with the CARS at baseline showed better outcomes for children having negative or low FRα antibody titers of the blocking type, up to 0.44 pmol FRα blocked/mL serum, versus the group whose FRα antibody titers were above 0.44. The baseline CARS score increased as a function of the age at which treatment was initiated. The outcome became poorer for the older subgroup of treated autistic children (Figure 3B). This outcome may be further compounded by the presence of maternal and paternal autoantibodies and embryonic exposure to these. Preliminary data suggested that in the event of maternal or parental FRα autoantibodies, the child´s outcome after treatment was also less favorable (Figure 3C).

This stumped me. How can paternal autoantibodies affect the embryo? Isn't this a typo? Maybe there is some indirect way of paternal antibodies affecting the unborn child? I googled but found nothing.

  • 3
    Frankly the whole FRAA-autism research is a bit shaky; I mean lots of low-quality studies. It's also unfortunately also often used by anti-vaxxers to claim a link between vaccines and autism (by passing a broad brush on [rare] auto-immunity side effects that are caused by some vaccines.) So, I'm pretty skeptical of such papers financed from relatively obscure sources... which the one you're citing from seems to be, alas.
    – Fizz
    Sep 12 at 9:07
  • @Fizz - thank you! Interesting review, and Open-Access to boot. Sep 12 at 10:25

I think you're right to be stumped.

The text you're referring to discusses Fig. 3C in the review; they note it's preliminary data but also seem to use strange/wrong descriptions, e.g. in the Fig 3 caption: "The presence of maternal FRα antibodies or presence of antibodies in both parents will negatively affect the treatment outcome."

I think someone just looked at Fig 3C (which lists patient, mother, father FRAb levels as +/-) and tried to come up with a result description without considering the underlying implications.

Just quickly looking at that section of the review, the Fig 3 graphs don't seem very convincing to me, as the error bars indicate a lot of overlap between the groups and it's unclear how much blind equivalent treatment there was (at least some of these are 2 year long interventions!). Fig 3C in particular seems to subdivide 82 patients into 6 FRAb categories, leaving very few per category and thus unclear statistical power.

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