Decreased Serum Hepatocyte Growth Factor (HGF) in Autistic Children with severe Gastrointestinal Disease

Abstract

Aim: To assess serum Hepatocyte Growth Factor (HGF) levels in autistic children with severe gastrointestinal (GI) disease and to test the hypothesis that there is a relationship between GI pathology and HGF concentration. Subjects and Methods: Serum from 29 autistic children with chronic digestive disease (symptoms for a minimum of 6-12 months), most with ileo-colonic lymphoid nodular hyperplasia (LNH-markedly enlarged lymphoid nodules) and inflammation of the colorectum, small bowel and/or stomach), and 31 controls (11 age matched autistic children with no GI disease, 11 age matched non autistic children without GI disease and 9 age matched non autistic children with GI disease) were tested for HGF using ELISAs. HGF concentration of autistic children with GI disease was compared to GI disease severity. Results: Autistic children with GI disease had significantly lower serum levels of HGF compared to controls (autistic without GI disease; p = 0.0005, non autistic with no GI disease; p = 0.0001, and non autistic with GI disease; p = 0.001). Collectively, all autistic children had significantly lower HGF levels when compared to non autistic children (p  0.0001). We did not find any relationship between severity of GI disease and HGF concentration in autistic children with GI disease. Discussion: These results suggest an association between HGF serum levels and the presence of GI disease in autistic children and explain a potential functional connection between the Met gene and autism. The concentration of serum HGF may be a useful biomarker for autistic children, especially those with severe GI disease.

iTRAQ‐Based Proteomic Analysis Reveals Protein Profile in Plasma from Children with Autism

“…Two proteins, that is, C5 and FERMT3 are being reported for the first time to be associated with autism. Likewise, we performed the FDR (false discovery rate) correction for [20,21] Alpha-1-antitrypsin (+) c) P01009 SERPINA1 37 50 2.07 2.94 4.27 [42,43] Alpha-actinin-1 (−) P12814 ACTN1 28 31 −3.91 −4.89 −4.21 [56,57] Alpha-enolase (−) P06733 ENO1 6 19 −1.02 −1.87 −2.34 [58] Angiotensinogen (+) c) P01019 AGT 21 31 3.31 5.71 4.77 [59] Apolipoprotein E (+) c) P02649 APOE 136 68 1.99 1.42 3.61 [47] Beta [25,61,62] Fibulin-1 (+) P23142 FBLN1 20 15 1.18 1.40 2.41 [31] Insulin-like growth factor -binding protein complex acid labile subunit (+) P35858 IGFALS 9 17 0.82 3.32 1.97 [57] Integrin alpha-IIb (−) P08514 ITGA2B 6 5.6 −2.03 −2.34 −3.23 [26] Kallistatin (+) c) P29622 SERPINA4 7 19 1.67 2.72 1.00 [59] Microtubule-associated protein RP/EB family member 2 (−) [27] a) (+), protein increased in abundant; (−), protein decreased in abundant. b) Fold change (log 2 ratio), p < 0.05 versus the control.…”

Decreased Epidermal Growth Factor (EGF) Associated with HMGB1 and Increased Hyperactivity in Children with Autism

“…It is possible that inflammatory cells, resulting from increased inflammation, are involved in the increased synthesis of GABA. Since decreased EGF has been associated with inflammatory conditions such as colitis23,24 and has been shown to have antiinflammatory effects,25 it is reasonable to suggest that low EGF could be associated with high inflammation in children with autism. Therefore, we suggest that increased GABA may be the result of decreased EGF, which results, in turn, in increased inflammation in children with autism.…”

Intracellular Pathways Associated with the Etiology of Autism

“…Our lab found HGF decreased in the serum of older autistic children with co-occurring GI disease when compared to non-autistic children with GI disease, autistic children without GI disease and healthy controls (non-autistic children without GI disease) [96]. The c-Met promoter variant rs1858830 reflects a common single-nucleotide polymorphism that increases the risk of ASD and is distinctively associated with ASD in individuals with co-occurring GI dysfunction [97].…”