Abstract
To assess the possible relationship between serum alpha-1 antitrypsin (AAT) levels and anti-neutrophil cytoplasmic antibodies (ANCA) in autistic children with severe GI disease and to test the hypothesis that there is an association between low serum AAT levels, the presence of ANCA and inflammatory GI disease seen in some autistic children. Serum from 40 autistic children with chronic digestive disease (many with ileo-colonic lymphoid nodular hyperplasia (LNH) and inflammation of the colorectum, small bowel and/or stomach), and 41 controls (21 age matched autistic children with no GI disease and 20 age matched children without autism or GI disease) were tested using ELISAs designed to quantitate ANCA (anti-PR3), AAT and PR3 levels. We found that a significant number of autistic children with chronic digestive disease had anti-PR3 ANCA, high serum PR3 and high severity of disease when compared to controls. This same group of autistic children had low serum levels of AAT compared to controls, which also correlated with the presence of anti-PR3 ANCA, high serum PR3, as well as the severity of intestinal disease, particularly LNH and severe erythema. These results suggest a relationship between low AAT levels, ANCA and severity of GI disease seen in a subpopulation of ASD individuals. We suggest that low AAT levels may result in high levels of PR3, which may, in turn be associated with the presence of ANCA.
Highlights
Alpha-1-antitrypsin (AAT), a 394 amino acid, 52 kDa glycoprotein synthesized by the liver, is the most abundant circulating serine protease inhibitor with normal serum concentration of 85–250 mg/dL.[1,2,3] AAT deficiency, caused by mutations in the AAT gene coding[4,5,6] on the long arm of human chromosome 14,[7] is a genetic condition that increases the risk of developing a variety of diseases including pulmonary emphysema, cirrhosis of the liver and gut disease
These results suggest a relationship between low AAT levels, anti-neutrophil cytoplasmic antibodies (ANCA) and severity of GI disease seen in a subpopulation of Autistic Spectrum Disorder (ASD) individuals
We suggest that low AAT levels may result in high levels of proteinase 3 (PR3), which may, in turn be associated with the presence of ANCA
Summary
Alpha-1-antitrypsin (AAT), a 394 amino acid, 52 kDa glycoprotein synthesized by the liver, is the most abundant circulating serine protease inhibitor with normal serum concentration of 85–250 mg/dL.[1,2,3] AAT deficiency, caused by mutations in the AAT gene coding[4,5,6] on the long arm of human chromosome 14 (locus 14q32.1),[7] is a genetic condition that increases the risk of developing a variety of diseases including pulmonary emphysema, cirrhosis of the liver and gut disease It is a naturally occurring inhibitor of proteinase 3 (PR3), one of the target antigens of anti-neutrophil cytoplasmic antibodies (cANCA).[8,9] An increased incidence of alpha 1-AT phenotypes associated with dysfunctional alpha 1-AT or low serum levels has been reported in patients with anti-PR3 antibodies.[10,11]. Autism may be apparent soon after birth, many autistic children experience at least several months, up to a year or more in some cases, of normal development—followed by regression, defined as loss of function or failure to progress.[24,25,26] Children with autistic spectrum disorders (ASD) frequently have accompanying gastrointestinal (GI) symptoms.[27,28,29]
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