Proteomic Biomarker Tests in Blood Samples from Children with Autism Spectrum Disorder (ASD)

There is accumulating evidence that at least a subset of children diagnosed with ASD also have aberrant immune functions. This study will attempt to identify more specifically the nature of the potential immune abnormalities in children.

The study will follow a case-control design, involving the following cohorts:

• young children (2-12 years) diagnosed with ASD
• children (12-18 years) diagnosed with ASD
• age- and sex-matched typically developing children
• high-risk infants (10-19 months) with at least one sibling with diagnosed ASD
• mothers of these high-risk infants
• young children (2-12 years) diagnosed with ASD and scheduled to undergo stem cell transplantation therapy (SCT)

Parents will be asked to complete several questionnaires relating to demographic and anamnestic details and to the child's development.

• A single blood draw from all participants will be performed in the clinic.
• A stool sample will be collected from high-risk infants.
• A stool and urine sample will be collected at home from children due to undergo SCT. For children scheduled to undergo SCT, the blood, stool and urine samples must be collected before therapy.

• Parents of high-risk infants will be contacted by phone or email when the child reaches diagnosable age (3.5 years) and again at the age of 6 years, to obtain an update on the child's ASD status. If the child has been diagnosed with ASD, an additional blood and stool sample may be collected.
• Children who underwent SCT will be contacted 2±1 months and 6±1 months after the first treatment session, for collection of additional blood samples. Stool and urine samples will be collected at the 6±1 month post-treatment visit as well. Should the child undergo additional SCT within two years of the first treatment, additional blood, stool and urine samples may be collected. At each subsequent visit, a parent/legal guardian will be asked to complete several short questionnaires.

Adverse events to blood drawing will be reported to the Data Coordinating Center using the appropriate Case Report Form (CRF).

In cases of adverse effects (AE) related to the drawing of blood or performance of examination of patients in the course of standard examination procedures, the investigating team will proceed in accordance with local guidelines (to be inserted by the PI), reporting the incidents which occurred during the course of a clinical trial.

Clinical data will be collected by the investigator, or a person appointed and appropriately trained by the investigator, and shall be entered into standardized CRFs and shared online with the sponsor. Source data will be retained for all data entered in the CRFs. Progress reports and the Final Report at the conclusion of the trial will be submitted to the regulatory authority and the Ethics Committee, as required.

Inclusion criteria

• Male and female children
• Child aged 2-12 years with diagnosed ASD according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (299.00) or DSM-V (299.00) OR Child aged 2-18 years diagnosed ASD according to DSM-IV (299.00) or DSM-V (299.00) AND scheduled to undergo stem cell transplantation OR Child aged 10-19 months not diagnosed with ASD but with a sibling diagnosed with ASD according to (DSM)-IV (299.00) or DSM-V (299.00) (herein termed "high-risk infants") OR Mothers of recruited high-risk infants OR A typically developing child aged 2-12 years with no signs of ASD or history of ASD in the immediate family
• Informed consent signed by the parent/legal guardian

Exclusion criteria

• Child and/or mother completed treatment with systemic steroids or immune suppressants less than 4 weeks before the screening visit
• Child and/or mother diagnosed with severe infectious diseases or sepsis over the last 6 months
• Child with ASD treated for a severe convulsive disorder (intractable seizures)
• Child and/or mother with hematological or malignant disorder
• For children in the SCT cohort: No new planned immune-modulating treatment (other than SCT) for at least 6 months before or after planned stem cell transplantation date
• If the PI suspects that the participant will not comply with study requirements, the participant may be excluded.