Cerebrospinal fluid and serum markers of inflammation in autism.
Systemic immune abnormalities have no known relevance to brain dysfunction in autism. In order to find evidence for neuroinflammation, we compared levels of sensitive indicators of immune activation: quinolinic acid, neopterin, and biopterin, as well as multiple cytokines and cytokine receptors, in cerebrospinal fluid and serum from children with autism, to control subjects with other neurologic disorders. In cerebrospinal fluid from 12 children with autism, quinolinic acid (P = 0.037) and neopterin (P = 0.003) were decreased, and biopterin (P = 0.040) was elevated, compared with control subjects. In sera from 35 persons with autism, among cytokines, only tumor necrosis factor receptor II was elevated compared with controls (P < 0.02). Decreased quinolinic acid and neopterin in cerebrospinal fluid are paradoxical and suggest dysmaturation of metabolic pathways and absence of concurrent infection, respectively, in autism. Alternatively, they may be produced by microglia but remain localized and not expressed in cerebrospinal fluid.
Zimmerman
Andrew W
AW
Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore Maryland 21205, USA.
Jyonouchi
Harumi
H
Comi
Anne M
AM
Connors
Susan L
SL
Milstien
Sheldon
S
Varsou
Angeliki
A
Heyes
Melvyn P
MP
D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000209:etiology; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D019798:Neopterin / Q000134:cerebrospinal fluid*; D020078:Neurogenic Inflammation / Q000150:complications / Q000276:immunology; D017378:Quinolinic Acid / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D016207:Cytokines; D019798:Neopterin; D017378:Quinolinic Acid