Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders

Abstract

Background: An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls.Methods: We obtained maternal mid-gestational serum specimens and newborn screening blood spots from the California Genetics Disease Screening Program (GDSP) for linked mother-baby pairs for 84 children with ASD and 49 children with developmental delay but not ASD (DD) identified from California Department of Developmental Services records and for 159 population controls sampled from birth certificates.Immunoglobulin levels in maternal and newborn specimens were measured by solid phase immunoassays and analyzed in logistic regression models for total IgG, total IgM, and Toxo IgG, and, for maternal specimens only, Toxo IgM. Correlations between maternal and newborn ranked values were evaluated.Results: In both maternal and newborn specimens, we found significantly lower risk of ASD associated with higher levels of Toxo IgG. In addition, point estimates for all comparisons were < 1.0 suggesting an overall pattern of lower immunoglobulin levels associated with higher ASD risk but most did not reach statistical significance. We did not find differences in maternal or newborn specimens comparing children with DD to controls.Discussion: These results are consistent with evidence from our prior study and other published reports indicating that immune factors during early neurodevelopment may be etiologically relevant to ASD. Lowered immunoglobulin levels may represent suboptimal function of the maternal immune system or reduced maternal exposure to common infectious agents.Conclusion: Patterns seen in these selected immunoglobulins may provide clues to mechanisms of early abnormalities in neurodevelopment contributing to ASD. We recommend further study of immunoglobulin profiles in larger samples of linked mother-baby pairs to evaluate possible etiologic relevance.

Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden

“…On the other hand, our results are consistent with results from a few studies investigating the relationship between maternal IgG antibodies directed against other specific antigens, such as those derived from Toxoplasma gondii (T. gondii), and ASD in offspring (24)(25)(26) in which high levels of maternal IgG were associated with decreased offspring risk of ASD.…”

“…It has also been hypothesized that risk associated with lower levels of maternal IgG represent an overall dysfunctional maternal immunity resulting in reduced levels of circulating IgG among mothers to children with ASD (24,25). This possibility is an unlikely explanation for our findings, since adjustment for maternal total IgG levels, measured in maternal sera, did not attenuate the associations between AGA and ASD observed maternal sera.…”

Autism spectrum disorder: advances in diagnosis and evaluation

“…Cross sectional studies of blood based biomarkers in newborn and infant samples may be more informative—for example, in one case-control study mRNA expression profiles in community identified toddlers with ASD differed from those of typically developing controls, with optimal sensitivity and specificity of 73% and 68%, respectively, in a cross validated sample 66. Maternal and newborn immunoglobulin levels have also been examined in relation to the risk of ASD,67 although no data on individual level prediction have been reported.…”

Common Genetic Variants Found in HLA and KIR Immune Genes in Autism Spectrum Disorder

“…Because HLA class II molecules are important in antibody production it would be interesting to know if there is an association between mothers who make these antibodies and certain DRB1 alleles. The entire area of maternal antibodies against fetal proteins, the production of autoantibodies, as well as antibodies to microbial pathogens should be studied more in ASD (Grether et al, 2016 ).…”