Innate Immunity in Autism Spectrum Disorders with Digestive Difficulties

Friday, May 12, 2017: 5:00 PM-6:30 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
M. Parellada1, M. J. Penzol2, A. Alcon3, K. McDowell4, L. Monteagudo3, J. C. Leza4 and B. García-Bueno5, (1)Hospital Gregorio Marañón, IiSGM, CIBERSAM, Madrid, Spain, (2)Child and Adolescent Psychiatry, Hospital Gregorio Marañon, CIBERSAM, IISGM, Madrid, Spain, (3)Hospital Gregorio Marañon, CIBERSAM, IISGM, Madrid, Spain, (4)Pharmacology, Universidad Complutense, Madrid, Spain, (5)Pharmacology, Universidad Complutense, CIBERSAM, Madrid, Spain

Among patients with Autism Spectrum Disorders (ASD), there is a high percentage suffering from functional Gastrointestinal Disorders (fGID). Some fGID have been thought of reflecting a systemic proinflammatory status. Evidence from different sources points towards the possibility that systemic innate immune/inflammatory mechanisms play an important role in some cases of ASD. The link between these potentially linked physiopathological markers has been hardly studied.


To explore whether a subset of children with ASD and fGID shows abnormalities in the Toll-like receptors (TLR4) proinflammatory signalling pathway.


This study included 53 subjects: 35 children with ASD (15 without- and 15 with fGID) and 20 controls (13 with and 5 without fGID). Mean age was 6.33 (range 3-10). 90 % were male. ASD was diagnosed following the AACAP recommendations (Volkmar, 2014) and fGID were assessed with the ROMA-III. Innate immune system: we assessed i and ii) Toll-like receptors 2 and 4, ii) Myeloid differentiation primary response gene 88 (MyD88), inicial element of this pathway and iv)TIR-domain containing protein TRIF (the sole adaptor of TLR3). Bivariate analyses were conducted in order to compare the levels of the different markers between subjects with ASD and without ASD and patients with and without fGID. ANCOVA analyses were conducted, with each marker as independent variable, and fGID status as covariate, to check for differences between ASD and no-ASD groups (fixed factor).


Kruskal-Wallis statistic showed that patients with ASD had higher PBMC levels of MyD88 than controls (31.77 and 17.72 respectively, chi-square 9.837, p=0.002). TLR-2 and TLR-4 were non-significantly higher in ASD than in controls (TLR2: 28.91 vs 23.28 p=0.071; TR4: 29.74 vs 21.67, p=0.071) and significantly higher in patients with fGID than in patients without fGID: TLR-4 (21.15 vs 36.65, p=0.000); TLR2 (30.76 vs 20.80 p=0.023). ANCOVA analysis confirmed that there was a diagnostic group effect on My88D and a fGID effect on TLR4 and TLR2 (See Table).


There seems to be a systemic proinflammatory status in patients with fGID irrespective of the presence of a diagnosis of ASD. ASD patients, irrespective of the presence of fGiD, show makers of activation in very early steps of the innate immune system. It seems worth studying the immunological pathophysiology of ASD for the ultimate goal of finding distinct subgroups of patients that can benefit for specific interventions.

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Lucas and Maes Mol Neurobiol 2013: 48:190–204