Increased serum albumin, gamma globulin, immunoglobulin IgG, and IgG2 and IgG4 in autism.

BACKGROUND: Research on the biological pathophysiology of autism has found some evidence that immune alterations may play a role in the pathophysiology of that illness. As a consequence we expected to find that autism is accompanied by abnormalities in the pattern obtained in serum protein electrophoresis and in the serum immunoglobulin (Ig) and IgG subclass profile. METHOD: We examined whether subjects with autism showed changes in total serum protein (TSP) and the serum concentrations of albumin, alpha1 globulin, alpha2 globulin, beta globulin and gamma globulins, IgA, IgM and IgG and the IgG subclasses IgG 1, IgG2, IgG3 and IgG4, compared with normal controls. RESULTS: We found significantly increased concentrations of TSP in autistic subjects, which were attributable to increased serum concentrations of albumin and gamma globulin. Serum IgG, IgG2 and IgG4 were also significantly raised. In autism there were significant and positive correlations between social problems and TSP and serum gamma globulin and between withdrawal symptoms and TSP and serum albumin and IgG. CONCLUSIONS: The results suggest that autism is characterized by increased TSP, a unique pattern obtained in serum protein electrophoresis, i.e. increased serum albumin and IgG, and by a specific IgG subclass profile, i.e. increased serum IgG2 and IgG4. The increased serum concentrations of IgGs in autism may point towards an underlying autoimmune disorder and/or an enhanced susceptibility to infections resulting in chronic viral infections, whereas the IgG subclass skewing may reflect different cytokine-dependent influences on autoimmune B cells and their products.

Pathophysiology of autism: current opinions.

Research on the neurochemical aspects of the pathophysiology of autism is still increasing and publications are abundant. In this paper we reviewed significant data from the last decade and recent research results from our center. We focused on molecules influencing the central nervous system (CNS) and consecutively responsible for typical autistic behavior. We highlighted the mutual relationship between the serotonergic, immunological and endocrinological system and the interaction of these three pivotal systems with predisposing (genetic)and external (pre-, peri- and postnatal) conditions and xenobiotics. We stressed the influence of age, pubertal stage, sex, race and IQ on biological data. There is growing evidence that the complexity and variability of those interactions might be responsible for the heterogeneity of behavioral phenotypes and biological findings in Autism. Genetic, neuroanatomical and neurophysiological data were mentioned according their relevance to neurochemical opinions.

Risperidone in the treatment of childhood autistic disorder: an open pilot study.

OBJECTIVE: To evaluate the tolerability and efficacy of risperidone in childhood autistic disorder. METHODS: A multicenter, open-label, dose-titration study involving seven autistic children (mean age 7.6 years) receiving risperidone for 4 weeks. RESULTS: Mean dose was 0.01 mg/kg/day on day 1, 0.019 mg/kg/day on day 7 (range 0.01-0.041 mg/kg/day) and 0.035 mg/kg/day on day 28 (range 0.014-0.064 mg/kg/day). Over the 4-week period, the Ritvo-Freeman Real Life Rating Scale total score measuring autistic behavior was significantly decreased (P = 0.019), as was the affectual reactions subscale (P = 0.029). Aberrant Behavior Checklist total score was significantly improved (P < 0.001), as were all subscales except inappropriate speech. Visual Analog Scale for individual target symptoms was significantly decreased (P = 0.001), and Clinical Global Impression severity of illness score was significantly improved (P = 0.006). The incidence of adverse effects was low, and no extrapyramidal symptoms were observed. No significant changes or clinically relevant abnormalities occurred in laboratory tests, vital signs or electrocardiograms. Plasma concentrations of the drug were similar to those in adult patients. CONCLUSIONS: These favorable results suggest that larger controlled trials of risperidone should be performed in autistic or mentally retarded patients with behavioral disturbances.

Peripheral markers of serotonergic and noradrenergic function in post-pubertal, caucasian males with autistic disorder.

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study group of 13 male, post-pubertal, caucasian autistic patients (age 12-18 y; I.Q. > 55) and 13 matched volunteers. [3H]-paroxetine binding Kd values were significantly higher in patients with autism than in healthy volunteers. Plasma concentrations of tryptophan, the precursor of 5-HT, were significantly lower in autistic patients than in healthy volunteers. There were no significant differences between autistic and normal children in the serum concentrations of 5-HT, or the 24-hr urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA), adrenaline, noradrenaline, and dopamine. There were no significant differences in [3H]-rauwolscine binding Bmax or Kd values, or in the serum concentrations of tyrosine, the precursor of noradrenaline, between both study groups. There were highly significant positive correlations between age and 24-hr urinary excretion of 5-HIAA and serum tryptophan. The results suggest that: 1) serotonergic disturbances, such as defects in the 5-HT transporter system and lowered plasma tryptophan, may play a role in the pathophysiology of autism; 2) autism is not associated with alterations in the noradrenergic system; and 3) the metabolism of serotonin in humans undergoes significant changes between the ages of 12 and 18 years.

Properties and engineering of a mutant STA promoter of Saccharomyces diastaticus.

A new allelic variant of the STA2 gene of S. diastaticus, designated as STA2K, was cloned and characterized (1; accompanying paper). An application-oriented analysis of the promoter region of STA2K is described, with an emphasis on its peculiar structural feature: A 1.1-kb natural deletion located 189 nucleotides upstream of the translation start codon. The strength of the STA2K promoter was found comparable to that of known strong constitutive yeast promoters (ADH1, GAPDH). Regulated glucoamylase expression was demonstrated by chimeric promoters, which were constructed by placing the STA2K promoter under the control of either the PHO5 or CYC1 upstream regulatory sequences. On high-copy-number vectors, induction of the UASPHO5-STA2K chimeric promoter by phosphate depletion resulted in a destructive overexpression of the secreted glucoamylase, which completely halted cell growth, and promoted cell decay. In contrast, UASCYC1 was shown to mediate a fine-tuned regulation both by glucose concentration and, indirectly, by starch, the substrate for the glucoamylase to produce glucose.