Abstract

We analyzed the catalytic activity of myelin basic protein (MBP) autoantibodies of the IgG class and compared its activity and specificity with homologous autoantibodies of the IgA class also found in sera of children with autistic spectrum disorders (ASD). Total IgG or IgA were purified from ASD patient serum utilizing affinity chromatography techniques. Both specific anti-MBP IgG or IgA autoantibodies were purified by immunoaffinity chromatography on MBP. The IgG or IgA proteolytic activities were measured using the chromogenic protease substrate S-2288 in the absence and presence of several divalent cations alone or in combination. The antigenic specificity of both IgG and IgA was determined by binding to immobilized MBP in competence with MBP COOH-terminal region peptides. Both IgG and IgA autoantibodies exhibit proteolytic activity; however, the IgG activity is metal-dependent, being significantly activated by the divalent cations Zn2+ and Mn2+. They both react with the MBP COOH-terminal region Leu109-Gly126. MBP is degraded by the IgG in the presence of Zn2+ and Mn2+. As observed with the IgA autoantibody, the IgG proteolytic activity is inhibited by several serine-proteinase inhibitors. The presence of autoantibodies to MBP in the serum of ASD patients suggests a possible role in the pathogenesis of this disease.