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.

Keywords: GI disease; autism; hepatocyte growth factor; met gene.

Figure 1.

The mean +/− SD HG F concentration (pg/ml) of 29 autistic children with chronic digestive disease (most with ileo-colonic lymphoid nodular hyperplasia (LNH) and inflammation of the colorectum, small bowel and/or stomach) (A GI), and 30 controls (11 age matched autistic children with no GI disease (A No GI), 11 age matched non autistic children without GI disease (NA no GI) and 9 age matched non autistic children with GI disease (NA GI)).

Figure 2.

HGF serum concentration was established for each individual by testing and correlating to known standards of various concentrations of MPO (8000 pg/ml–125 pg/ml), as well as negative control (serum diluent alone).

Figure 3.

Serum HGF concentration was measured in a typical ELISA. Two autistic children with GI disease (A GI), 2 non autistic children with GI disease controls (NA GI), 2 autistic children with no GI disease (A No GI) and 2 non autistic children with no GI disease controls (NA no GI) were tested. Four replicate samples were tested for each individual.

Figure 4.

A Box Plot representation of HGF levels showing variability in autistic and non autistic groups (with and without GI disease).