Anti-phospholipid antibodies and autism

Regular readers are probably quite tired of hearing me go on about autoimmunity and autism. It's a research topic which seems to come up pretty regularly these days for all manner of reasons and in all manner of places (see here). Indeed, now even being linked to the new kid on the block that is MAR autism (see here).

As I've mentioned before, I don't think we can quite say that all autism (all of the autisms sorry) 'are autoimmunity' because immune function is a pretty varied thing when it comes to autism. But there is a growing evidence base to suggest that we should be looking into this issue with much greater assiduity for at least some on the autism spectrum and whether markers of autoimmunity might be related to presented symptoms or at the very least, affecting aspects of quality of life.

A further addition to the area of autoimmunity and autism is that of the paper by Careaga and colleagues* who quite recently reported on the presence of increased anti-phospholipid antibodies** in a cohort of children diagnosed with an autism spectrum condition as part of the CHARGE study.

As per the very informative description by Misita and Moll**, anti-phospholipid antibodies (APLAs) reflect activity by the immune system against a class of substances called phospholipids which are a vitally important part of cell membranes. Some of the main issues associated with the presence of APLAs relates to blood clots and pregnancy loss as per the description of anti-phospholipid syndrome (APS) or Hughes syndrome.

Careaga et al (carrying quite an impressive authorship list it has to be said) looked at the presentation of various APLAs across three groups: children diagnosed with an autism spectrum disorder (ASD) (n=54), children diagnosed with a developmental delay (but not autism) (n=22) and typically developing controls (n=33). They looked at antibodies to anticardiolipin, antiphosphoserine, and anti-β2-glycoprotein 1 across each of the groups and further whether levels of these APLAs correlated with specific behaviours or impairments in behaviours.

The results: well, comparing the autism group vs. the typically developing group, levels of each of the APLAs were higher in autism (and significantly so). Aside from the cardiolipin antibodies, the other APLAs were also significantly higher in the autism group compared with the developmental delay group too. Ergo, another study finding "increased presence of autoantibodies in children with ASD". When examined alongside various behavioural functions derived from schedules such as the VABS, there were also some significant correlations noted (see here) but "no significant differences found when analyzing within the individual groups based on diagnosis".

It is worth pointing out that although these APLAs were detected in higher concentrations in the autism group (a) not every child with autism had significant elevations in these antibodies and (b) "the levels are below what is considered clinically significant levels for APS". Importantly too that even if levels of APLAs were getting into the APS diagnostic range, the study results in themselves probably wouldn't be able to diagnose APS given the need for two separate testing occasions (see here) and other criteria.

Looking at some of the published research literature around APLAs, I stumbled across a few potentially important connections. Abisror and colleagues*** reported on some preliminary observations of offspring autism in children born to mums with APS. This following similar preliminary reporting (see here) bearing in mind that a chance association cannot at this point, be ruled out. That being said, all that recent chatter about MAR autism (see here) and maternal immune activation and behavioural issues (see here) must also be thrown into the research mix too. When looking also at a condition like attention-deficit hyperactivity disorder (ADHD) however, which has more than once been linked to cases of autism (see here), other investigations have not found any relationship between APLAs and behavioural presentation****. So one needs to remain a little guarded about how the Careaga results will eventually pan out.

I do think there is more to do in the area of APLAs and autism. The link between APLAs during pregnancy and adverse birth outcomes such as preterm birth (see here) and low birth weight (see here) must be seen as important confounding variables given the complicated links made in these areas with offspring autism risk (see here). The findings that at least some people with APLAs will eventually go on to be diagnosed with autoimmune conditions such as systemic lupus erythematosus (SLE) or related mixed connective tissue disorder is also worthy of greater investigation; indeed whether conditions like SLE are likely to be more prevalent among mums and dads of children with autism (as per the recent suggestion) particularly those with elevated APLAs (oh, we're back to MAR autism again).

I'm gonna stop there for now. On purpose I've not headed too far into the mechanism of how elevated levels of APLAs detected in cases of autism might work, simply because I'd rather see some independent replication of these results first before heading down the path of speculation. But still I remain very interested in the Careaga findings....

Some music to close, and in memory of Lou Reed, a Velvet Underground special: I'm Waiting for the Man.

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* Careaga M. et al. Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders. Mediators of Inflammation. 2013: 935608.

** Misita CP. & Moll S. Antiphospholipid Antibodies. Circulation. 2005; 112: e39-e44.

*** Abisror N. et al. Autism spectrum disorders in babies born to mothers with antiphospholipid syndrome. Semin Arthritis Rheum. 2013 Jul 30. pii: S0049-0172(13)00149-2. doi: 10.1016/j.semarthrit.2013.07.001.

**** Bujanover S. et al. Lack of association between anti-phospholipid antibodies (APLA) and Attention Deficit/Hyperactivity Disorder (ADHD) in children. Clin Dev Immunol. 2003 Jun-Dec;10(2-4):105-9.

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Milo Careaga,Robin L. Hansen,Irva Hertz-Piccotto,Judy Van de Water,Paul Ashwood (2013). Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders Mediators of Inflammation DOI: 10.1155/2013/935608