Association of IL-12p70 and IL-6:IL-10 ratio with autism-related behaviors in 22q11.2 deletion syndrome: A preliminary report |
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| Institution: | 1. Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA;2. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA;3. Children’s Healthcare of Atlanta and Nell Hodgson Woodruff School of Nursing at Emory University, Atlanta, GA, USA;1. Institute of Biological Psychiatry, Copenhagen Mental Health Services, Roskilde, Denmark;2. Mental Health Center Copenhagen, Copenhagen Mental Health Services, Roskilde, Denmark;3. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark;4. Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark;5. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;6. Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA;7. National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark;8. Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark;9. Department of Biomedicine, Aarhus University, Aarhus, Denmark;10. Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark;11. Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark;12. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;13. Department of Human Genetics, Department of Psychiatry, Center for Neurobehavioral Genetics, and Neurogenetics Program, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;14. Department of Family Medicine and Public Health, University of California, San Diego, CA, USA;1. Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California;2. Department of Psychology, University of California, Los Angeles, Los Angeles, California;3. Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, California;4. Department of Neurobiology, University of California, Los Angeles, Los Angeles, California;5. Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania;6. Developmental Neurogenomics Unit, Human Genetics Branch, National Institute of Mental Health, Bethesda, Maryland;1. Division of Rheumatology, Allergy, and Clinical Immunology, Department of Internal Medicine, University of California, Davis, Davis, California;2. MIND Institute, University of California, Davis, Davis, California;3. Department of Pediatrics, University of California, Davis, Davis, California;4. Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California;5. Division of Research, Kaiser Permanente Northern California, Oakland, California;6. Environmental Health Investigations Branch, California Department of Public Health, Richmond, California;7. Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland;1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan;2. Consumer Healthcare Products Development, Zeria Pharmaceutical Co., Ltd., 10-11 Nihonbashi Kobuna-cho, Chuo-ku 103-8351, Tokyo, Japan;3. Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara 324-8501, Tochigi, Japan |
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| Abstract: | 22q11.2 deletion syndrome (22q11DS) is a genetic disorder that conveys a significant risk for the development of social behavior disorders, including autism and schizophrenia. Also known as DiGeorge syndrome, 22q11DS is the second most common genetic disorder and is characterized by an elevated risk for immune dysfunction, up to 77% of individuals have an identifiable immune deficiency. We hypothesize that this immune dysfunction could contribute to the elevated risk of impaired social behavior seen in 22q11DS. The current study begins to elucidate these immune deficits and link them with the behavioral alterations associated with the disorder. Serum concentrations of a series of cytokines were examined, using a multiplex immunoassay, in sixteen individuals with 22q11DS and screened for autism-related behavior using the Autism Diagnostic Interview-Revised (ADI-R). This preliminary study examined correlations between specific immune proteins and each of the ADI-R algorithm scores (social, communication, and repetitive behavior). The inflammatory cytokine IL-1β, as well as the ratio between the inflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10, were correlated with social scores (r = 0.851, p = 0.004; r = 0.580, p = 0.018). In addition, the inflammatory cytokines interferon gamma and IL-12p70 were correlated with repetitive behaviors (r = 0.795, p = 0.033; r = 0.774, p = 0.002). Interestingly, IL-12 has been reported to be increased in autistic children. These data show a positive association between severity of autism-related behaviors and level of serum concentrations of inflammatory cytokines in individuals with 22q11DS, providing a basis for further inquiry. |
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