Heat shock protein and gliadin peptide promote development of peptidase antibodies in children with autism and patients with autoimmune disease.
Clin Diagn Lab Immunol. 2004 May;11(3):515-24. PMID: 15138176
Section of Neuroimmunology, Immunosciences Lab., Inc., 8693 Wilshire Blvd., Suite 200, Beverly Hills, CA 90211, USA. firstname.lastname@example.org
Searching for a mechanism underlying autoimmunity in autism, we postulated that gliadin peptides, heat shock protein 60 (HSP-60), and streptokinase (SK) bind to different peptidases resulting in autoantibody production against these components. We assessed this hypothesis in patients with autism and in those with mixed connective tissue diseases. Associated with antigliadin and anti-HSP antibodies, children with autism and patients with autoimmune disease developed anti-dipeptidylpeptidase I (DPP I), anti-dipeptidylpeptidase IV (DPP IV [or CD26]) and anti-aminopeptidase N (CD13) autoantibodies. A significant percentage of autoimmune and autistic sera were associated with elevated immunoglobulin G (IgG), IgM, or IgA antibodies against three peptidases, gliadin, and HSP-60. These antibodies are specific, since immune absorption demonstrated that only specific antigens (e.g., DPP IV absorption of anti-DPP IV), significantly reduced IgG, IgM, and IgA antibody levels. For direct demonstration of SK, HSP-60, and gliadin peptide binding to DPP IV, microtiter wells coated with DPP IV were reacted with SK, HSP-60, and gliadin. They were then reacted with anti-DPP IV or anti-SK, anti-HSP, and antigliadin antibodies. Adding SK, HSP-60, and gliadin peptides to DPP IV resulted in 27 to 43% inhibition of the DPP IV-anti-DPP IV reaction, but DPP IV-positive peptides caused 18 to 20% enhancement of antigen-antibody reactions. We propose that (i) superantigens (e.g., SK and HSP-60) and dietary proteins (e.g., gliadin peptides) in individuals with predisposing HLA molecules bind to aminopeptidases and (ii) they induce autoantibodies to peptides and tissue antigens. Dysfunctional membrane peptidases and autoantibody production may result in neuroimmune dysregulation and autoimmunity.