A Rapid and Simple Blood Test to Identify Gastrointestinal Inflammation in Children with ASD
Abstract
Chronic gastrointestinal (GI) symptoms are a frequent comorbid finding in children with autism spectrum disorder (ASD), occurring in up to 70% of children in prospective, systematic studies. GI symptoms consist of diarrhea, constipation, abdominal distension, failure to thrive, weight loss, gastroesophageal reflux (GERD), rumination, food refusal, and abdominal pain. There is increasing recognition that untreated underlying GI pathology contributes significantly to symptoms previously considered solely “behavioral” in nature (e.g., aggression, self-injury, hyperactivity) and that children with ASD develop novel ways of expressing their discomfort due to their global deficits in both verbal and nonverbal communication. The overall impact of these chronic GI symptoms intensifies core ASD deficits and their attendant effect on familial quality of life. Common etiologies (i.e., diagnoses) of GI symptoms in ASD include GERD, acid-peptic disease, eosinophilic esophagitis, and an ASD-associated enterocolitis (ASDEC). The latter diagnosis is exceedingly frequent, occurring in up to 73% of ASD children undergoing diagnostic endoscopy for their chronic GI symptoms. ASD-associated enterocolitis has been the focus of much of our prior research and publications. Currently, there are no molecular-based diagnostic markers (biomarkers) for ASDs or comorbid medical pathologies. Lack of such markers often delays accurate diagnosis of both the ASD and GI comorbidities until symptom progression is advanced, resulting in missed opportunities for early diagnosis and intervention. The importance of early intervention (behavioral and medical) in developmental disorders such as ASD has been well established. Additional benefits of molecular characterization of an ASDEC phenotype include a foundational mechanistic framework from which targeted therapeutic strategies can be developed. Our work currently focuses on the specific diagnosis of autism-associated inflammatory bowel disease (ASDEC) and has resulted in the only published reports of the molecular characterization of this condition. Since 2003, we have been collecting and archiving clinical information and biomaterials (biopsy tissue and peripheral blood taken during clinically indicated ileocolonoscopy procedures) from children with ASD and chronic GI symptoms refractory to empiric GI therapy. This tissue bank, amassed over 15 years under Institutional Review Board (IRB) approval and oversight, funded exclusively through private funding, now contains clinical data and archived tissues (mucosal biopsies, whole blood, serum and plasma) from >1500 individual children with ASD and comorbid GI symptoms. We continue to add 3-5 new cases each month. We have also archived GI tissue, whole blood, and serum (obtained during endoscopy) from >400 typically developing (TD) children under a separate IRB. Specimen collection from all patient groups is ongoing. In Aim 1 of this proposed work, we will compare blood gene expression from four groups of children: (1) ASD with GI inflammation, (2) ASD without GI symptoms, (3) TD with GI symptoms, and (4) TD without GI symptoms. These profiles will be used to identify (Aim 1) and validate (Aim 2) gene expression that is unique to Group 1. Through statistical modeling, we will derive a blood-based biomarker for ASD-associated intestinal inflammation. Next, we will test the biomarker in a set of patient samples collected before (pre-) and after (post-) successful treatment for GI inflammation. By correlating the pre- and post-treatment levels of this biomarker with clinical outcome (i.e., resolution of GI symptoms), the clinical usefulness of the biomarker can be assessed (Aim 3). This application is highly responsive to two of the key areas of research stated to be of particular interest to this Idea Development Award Research Program: (1) mechanisms underlying conditions co-occurring with ASD and (2) mechanisms of heterogeneous clinica
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110294
Entities
People
- Stephen Walker
Organizations
- United States Army
- Wake Forest University