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

Abstract

ObjectiveIndividuals diagnosed with autism spectrum disorders (ASD) are reported to have higher levels of antibodies directed towards gliadin, a component of wheat gluten. However, no study has examined such antibodies in etiologically-relevant periods before diagnosis. The objective of this study is to investigate if maternal levels of immunoglobulin G antibodies directed at gliadin, during pregnancy and at the time of birth, are associated with ASD in offspring. MethodsIn this population-based study set in Sweden with 921 ASD cases and 1090 controls, we analyzed levels of anti-gliadin antibodies (AGA) in archived neonatal dried blood spots (NDBS, as maternal IgG is transferred to the fetus) and in paired maternal sera collected earlier in pregnancy for a subset of 547 cases and 428 controls. We examined associations to any ASD diagnosis and considering common comorbidities (i.e. intellectual disability [ID] and attentiondeficit/hyperactivity disorder [ADHD]). We compared 206 ASD cases to their unaffected siblings to examine the potential for confounding by shared familial factors. ResultsHigh levels (³90 th percentile) of maternal AGA were associated with decreased odds of ASD, particularly ASD with comorbid ID, when measured in NDBS (OR 0.51, 95% CI 0.30-0.87) with a similar trend in maternal sera (0.55, 0.24-1.29). High levels of maternal AGA were similarly associated with lower odds of ASD with ID in the sibling comparison. ConclusionsThis first study of exposure to AGA in the pre-and perinatal periods suggests that high levels of maternal AGA are associated with lower odds of ASD with ID. SF2. Maternal IgG AGA levels during pregnancy and offspring odds of ASDThe figure displays crude and adjusted OR's and 95 % CI for high levels of maternal AGA (i.e. levels in the 80-90 and > 90 th percentile categories, based on the distribution among controls) when measured in NDBS and in MS, for ASD in offspring as well as for ASD subtyped by comorbidities. The adjusted models for AGA in NDBS were adjusted for sex, maternal age, maternal BMI, maternal psychiatric history, maternal immigrant status, income, birth order, gestational age at birth and mode of delivery. The adjusted models for AGA in MS were adjusted for sex, maternal age, maternal BMI, maternal psychiatric history, maternal immigrant status, income, maternal total IgG and birth order.Abbreviations; ADHD = Attention-deficit hyperactive disorder, AGA = Antigliadin antibodies, ASD = Autism spectrum disorders, CI = Confidence interval, ID =Intellectual disability, MS = Maternal, NDBS = Neonatal dried blood spots, OR = Odds ratio

Celiac Disease and Its Association with Organ-Specific Auto-Immune Diseases

“…This provides the child with the passive immunity against the antigens (Slifka & Amanna, 2018). A recent study conducted by Gardner et al, showed that the high level of maternal anti-gliadin antibodies protects the child against ASD (Gardner et al, 2020).…”