Low serum Alpha-1 Antitrypsin Associated with Anti-PR-3 AncA in Autistic Children with GI Disease

Abstract

Aim: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. Subjects and Methods: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. Results: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. Discussion: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.

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

“…Thus, the complement system in the periphery of subjects with ASD may be activated . Low levels of SERPINA1 have been observed in some children with autism, which is inconsistent with our finding and need further confirmation. Activation of complement pathway can ultimately lead to the release of inflammatory mediators.…”

“…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 serum Ou/Zn sOD in children with Autism

“…Evidence suggests that increased oxidative stress is associated with autism, with likely contributions from environmental, 46,47 genetic 48–51 and immunological 52–58 factors. This may be due to (a) increased production of endogenous pro-oxidants (such as NO, xanthine oxidase, homocysteine) 59–64 or environmental pro-oxidants, 65,66 or deficiencies of antioxidants (ceruloplasmin, transferrin, superoxide dismutase, glutathione peroxidase, catalase, reduced glutathione), or both.…”

Generalized Autoimmunity of ANCA and ASCA Related to Severity of Disease in Autistic Children with GI Disease

“…30 We have also reported that a significant number of autistic children with chronic digestive disease have anti-PR3 ANCA, low serum AAT, and high serum PR3, which correlate with high severity of GI disease, suggesting that high PR3 levels may be causing ANCA in autistic children with severe GI problems. 31 Because of this, we hypothesized that the autoimmune response in this sub group of autistic children might be general, so we tested the same population for ASCA.…”