Autoantibodies and autism again

Autoantibodies - that is, antibodies directed at the body itself - are no stranger to autism research. I've talked about various types of autoantibody being detected in elevated levels in certain groups and cases of autism (see here for example). The paper by Gehan Mostafa and colleagues [1] adds to the roll call with their findings: "The seropositivity of anti ds-DNA and/or ANA [antinuclear antibodies] in autistic children was 42%".

Charge ! @ Wikipedia 

Before progressing to some of the details of this study I should mention that this research team have some 'form' in this particular area of autism research [2] (open-access here). In fact, I've talked about their work several times on this blog; the entry perhaps most relevant to the latest paper was on some of their data on the presence of anti-MAG (anti-myelin associated glycoprotein) and anti-MAP (anti-myelin basic protein) antibodies in cases of autism (see here).

A few points to note from the latest paper:

• Blood samples were provided by 100 children diagnosed with an autism spectrum disorder (ASD) aged between 4-11 years old. Serum levels of anti-ds-DNA and antinuclear antibodies (ANA) were measured and levels compared with a control group of 100 asymptomatic children. As the names suggest, anti-ds-DNA antibodies and ANA(s) target the cell nucleus and in particular double-stranded DNA (as per the ds in the title). 
• "The seropositivity of anti ds-DNA antibodies and ANA in autistic children was 34% and 25%, respectively. In addition, 42% of autistic children were seropositive for anti ds-DNA antibodies and/or ANA".
• The relationship (if I can call it that) between seropositivity to anti ds-DNA antibodies and a familial history of autoimmune conditions was also interesting.

The authors call for further work in this area which I would very much second "to validate whether these antibodies are a mere association or have a pathogenic role in some autistic children". As far as I can ascertain ANA and anti ds-DNA antibodies are very much tied into the condition systemic lupus erythematosus (SLE) as per studies like this one [3] (open-access). The insinuation being that where present one might consider other screening to rule out a comorbid diagnosis of SLE alongside autism; even the possibility of clusters of SLE pathology [4]. I might also at this point bring in some interesting work on anti-phospholipid antibodies (APLAs) which was talked about on this blog a few months back (see here) in light of a proposed SLE-autism connection.

The suggestion of a widened link between anti ds-DNA antibodies "pathogenic to the brain as well as to the kidney" was also something which caught my eye. The very interesting paper by Diamond and colleagues [5] for example, hinted at cross-reactivity of anti ds-DNA antibodies and "N-methyl-d-aspartate receptor (NMDAR) on neurons". On reading this, I was immediately brought back to the case report by Scott and colleagues [6] concerning anti-N-methyl-D-Aspartate (NMDA) receptor encephalitis and autistic regression (see here). I'm not necessarily saying that the two issues are one and the same, merely that there might be a bigger picture here potentially connecting the various dots.

Finally, as per their previous paper reporting: "Serum levels of antinucleosome-specific antibodies were increased in some autistic children" [2] the family history of autoimmunity also crops up again in their current publication. There is no getting away from the fact that autoimmunity crops up time and time again when talking about autism and the extended family (see here). The fact that a family history of autoimmunity or autoimmune conditions seemed to play something of a modifying role for the presence of various autoantibodies is perhaps not surprising but could lead down some new research paths.

To close, a tribute to the lifetime of work from Lorna Wing and her invaluable contribution to autism (RIP).

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[1] Mostafa GA. et al. Systemic auto-antibodies in children with autism. J Neuroimmunology. 2014. April 26.

[2] Al-Ayadhi LY. & Mostafa GA. Serum antinucleosome-specific antibody as a marker of autoimmunity in children with autism. J Neuroinflammation. 2014 Apr 3;11(1):69.

[3] Al-Shamahy H. et al. Clinical and Laboratory Manifestations of Yemeni Patients with Systemic Lupus Erythematosus. Sultan Qaboos Univ Med J. Feb 2014; 14(1): e80–e87.

[4] Li PH. et al. Relationship between autoantibody clustering and clinical subsets in SLE: cluster and association analyses in Hong Kong Chinese. Rheumatology (Oxford). 2013 Feb;52(2):337-45.

[5] Diamond B. et al. Moving towards a cure: blocking pathogenic antibodies in systemic lupus erythematosus. J Intern Med. Jan 2011; 269(1): 36–44.

[6] Scott O. et al. Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis: An Unusual Cause of Autistic Regression in a Toddler. J Child Neurol. 2014 May;29(5):691-4.

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Mostafa, G., El-Sherif, D., & Al-Ayadhi, L. (2014). Systemic auto-antibodies in children with autism Journal of Neuroimmunology DOI: 10.1016/j.jneuroim.2014.04.011