Date of Award:

5-1-1988

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Biology

Department name when degree awarded

Biology (Human Immunology)

Committee Chair(s)

Reed P. Warren

Committee

Reed P. Warren

Committee

Frederick Post

Committee

James A. Gessaman

Committee

Ronald Canfield

Committee

Dennis O. Dell

Committee

LeGrande Ellis

Abstract

Autism is a severe behaviorally defined disorder with a cause (or causes) that is still unknown. The objective of this study was to explore the possibility that autoreactivity against nuclear antigens is associated with this severe developmental disorder. Sera of autistic patients were tested for the presence of antibodies which were reactive with one or more of eight nuclear antigens including double-stranded deoxyribonucleic acid (DS-DNA), single-stranded deoxyribonucleic acid (SS-DNA), histone, deoxyribonucleoprotein (DNP), ribonucleoproteins Ro/SS-A and La/SS-B, RNP, and Smith's antigen (SM). Sera of autistic patients were found to be reactive with four of the nuclear antigens. These antigens included RNP, Ro/SS-A, SM, and histones with frequencies of 28% (sera from 8 of 29 patients were positive), 21% (6 positive of 29), 14% (4 of 29), and 13% (4 of 32), respectively. In contrast, sera of normal healthy subjects had positive frequencies of 7% (1 positive of 14 studied), 8% (1 of 12), 7% (1 of 13), and 6% (2 of 31). Some reactivity was detected in autistic patients' sera against DSDNA and DNP antigens with frequencies of 6% (2 of 36) and 3% (1 of 29), respectively, as compared to 0% in normal subjects. There was no reactivity for anti-SS-DNA antibodies in the sera of autistic or normal subjects, and there was no reaction against La/SS-B in sera of autistic and normal subjects. A correlation between immune function and the antinuclear antibodies was revealed. Fifty-six percent (9 of 16) of the autistic patients with antinuclear antibodies had a depressed response to the T-cell mitogen concanavalin-A (Con-A) parameter and a low helper/supressor (0KT4/0KT8) ratio. Fifty percent (8 of 16) of these patients with antinuclear antibodies demonstrated low levels of T-lymphocytes in their peripheral blood as compared to 18% (2 of 11) of the autistic patients without antinuclear reactivity (P < 0.05). Also, 4 of 5 (80%) autistic patients produced reduced levels of interleukin-2, and 9 of 12 (67%) of the autistic patients had abnormally high levels of interleukin-2 receptors in their plasmas.

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