Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome.
Using a double-antibody immunoaffinity assay (Luminex) and ELISA technology, we measured concentrations of certain neurotrophins, neuropeptides, and cytokines in pooled samples (one to three subjects per sample) eluted from archived neonatal blood of children with later-diagnosed autism, Down syndrome, very preterm birth, or term control infants. We also measured analytes in blood from healthy adult controls. Case or control status for infant subjects was ascertained by retrospective review of service agency medical records. We observed inhibitory substances in eluates from archived bloodspots, especially marked for measurement of BDNF. Concentrations in control subjects differed by age: BDNF rose markedly with age, while NT-3 and NT-4/5 concentrations were lower in adults than in newborn infants. IL-8 concentrations were higher in newborn infants, preterm and term, than in adults. Considered by diagnostic group, total protein was higher in Down syndrome than in either autism or control subjects. In infants with Down syndrome, concentrations of IL-8 levels were higher than in controls, whether or not corrected for total protein; NT-3 and CGRP were lower and VIP higher. In samples from autistic subjects, NT-3 levels were significantly lower than controls and an increase in VIP approached statistical significance. Concentrations of NT-4/5 and CGRP were correlated in infants with autism but not in Down syndrome or controls. Some of these results differ from earlier findings using a single-antibody recycling immunoaffinity chromatography (RIC) system. We discuss interrelationships of VIP, NT-3 and IL-8 and their potential relevance to features of the neuropathology of autism or Down syndrome.
Nelson
Phillip G
PG
National Institute of Child Health and Development, Building 31, Room 2A25, Bethesda, MD 20892-2426, USA. nelsonp@mail.nih.gov
Kuddo
Thea
T
Song
Eun Young
EY
Dambrosia
James M
JM
Kohler
Shawn
S
Satyanarayana
Gowri
G
Vandunk
Cassandra
C
Grether
Judith K
JK
Nelson
Karin B
KB
D000328:Adult; D000367:Age Factors; D000818:Animals; D001321:Autistic Disorder / Q000097:blood*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D002648:Child; D004314:Down Syndrome / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000097:blood*; D009414:Nerve Growth Factors / Q000097:blood; D020933:Neurotrophin 3 / Q000097:blood*; D011247:Pregnancy; D012189:Retrospective Studies; D014660:Vasoactive Intestinal Peptide / Q000097:blood*
D019208:Brain-Derived Neurotrophic Factor; D016209:Interleukin-8; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D014660:Vasoactive Intestinal Peptide; D015740:Calcitonin Gene-Related Peptide; C073922:neurotrophin 4