Cerebrospinal Fluid and Serum Markers of Inflammation in Autism

Zimmerman AW (1,2), Jyonouchi H (3), Comi AM (2), Connors SL (1), Milstien S (4), Varsou A (5), Heyes MP (4,6)
(1) Dept. of Neurology & Developmental Med, Kennedy Krieger Institute, Baltimore, MD; (2) Johns Hopkins Univ. School of Medicine; (3) New Jersey Medical School; (4) National Institutes of Health; (5) Univ. of Athens School of Medicine; (6) PsychoGenics, Inc.

Abstract: Pediatric Neurology, 2005 Sep;33(3):195-201

Findings

Immune system abnormalities have been reported in autism but there is no known link between systemic immune findings measured by peripheral blood samples (i.e. outside the central nervous system) and immune findings within the central nervous system. If the immune findings in peripheral blood are relevant to the development of autism, there should be corresponding immune activation in the central nervous system, demonstrated by markers of inflammation in cerebrospinal fluid (CSF).  Zimmerman and colleagues examined CSF and peripheral blood samples from 12 children with autism and CSF from 27 children with neurologic diagnoses, but without histories of inflammatory disorders. The authors also obtained blood samples from an additional 35 children with autism, 11 children with other neurologic disorders, and 12 typically developing children (10 of whom were siblings of children with autism).

Two sensitive markers of inflammation, quinolinic acid and neopterin, were much lower in the CSF of the children with autism compared with the neurologic control subjects, a paradoxical finding. Another marker, biopterin, was elevated compared to controls, but biopterin does not increase with infection. Elevated biopterin does not indicate a typical inflammatory process but could indicate reduced or dysregulated immune activity. In blood samples, tumor necrosis factor receptor II was the only inflammatory marker elevated in children with autism compared with controls.

Conclusions

The authors did not find evidence of inflammation in the brains of the children with autism, as measured by markers of inflammation in CSF. The study results may suggest delayed maturation of immune activity and absence of infection in the brains of the children with autism. Another possibility is that the two reduced markers of inflammation, quinolinic acid and neopterin, might be produced by microglia (the major immune cells in the central nervous system) but remain localized with no diffusion into the cerebrospinal fluid.