Amniotic fluid inflammatory cytokines: Potential markers of immunologic dysfunction in autism spectrum disorders

Abstract

Objectives. The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy. Methods. AF samples of 331 ASD cases and 698 controls were analyzed for inflammatory cytokines using Luminex xMAP technology utilizing a historic birth cohort. Clinical data were retrieved from nationwide registers, and case-control differences in AF cytokine levels were assessed using chi-square tests, logistic and tobit regression models. Results. Overall, individuals with ASD had significantly elevated AF levels of TNF-α and TNF-β compared to controls. Analyzing individuals diagnosed only with ICD-10 codes yielded significantly elevated levels of IL-4, IL-10, TNF-α and TNF-β in ASD patients. Restricting analysis to infantile autism cases showed significantly elevated levels of IL-4, TNF-α and TNF-β compared to controls with no psychiatric comorbidities. Elevated levels of IL-6 and IL-5 were found in individuals with other childhood psychiatric disorders (OCPD) when compared to controls with no psychiatric comorbidities. Conclusions. AF samples of individuals with ASD or OCPD showed differential cytokine profiles compared to frequency-matched controls. Further studies to examine the specificity of the reported cytokine profiles in ASD and OCPD are required.

Key words::

• Autistic disorder
• amniotic fluid
• cytokines
• birth cohort
• maternal immune activation

Acknowledgements

The authors thank Lasse S. Jønsson from Statens Serum Institute (SSI) and Maria Pryds for their assistance in data retrieval and Vibeke Munk from University of Copenhagen for her administrative assistance. We also thank SSI Luminex Lab technical staff for their time and efforts. The Danish Historic Birth Cohort was established at Statens Serum Institute, Copenhagen with a grant from The Danish Medical Research Foundation and The Danish Ministry of the Interior and Health (Project no. 271–05-0523/09-060179).This study is funded by Aarhus University Faculty of Health Sciences, Aarhus, Denmark and Statens Serum Institute, Department of Clinical Biochemistry and Immunology, Copenhagen, Denmark (Project Title: Intrauterine Exposures and Childhood Psychiatric Disorders, Project ID: 494028).

Statement of Interest

None to declare.