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Autoantibody signatures in children with celiac disease, juvenile idiopathic arthritis, and polyautoimmunity
Nan Du1, Denis Chang1, Madison Wong1
1Division of Gastroenterology and Nutrition Boston Children's Hospital, Harvard Medical School Boston Massachusetts USA.
Insights
Multiplex autoantibody arrays identified higher autoantibody levels in children with polyautoimmunity. Specific autoantibodies like H/K ATPase were elevated in children with celiac disease and polyautoimmunity.
Area of Science:
- Immunology
- Pediatrics
- Biomarker Discovery
Background:
- Autoimmune diseases are common in children.
- Identifying novel biomarkers for polyautoimmunity is crucial for early diagnosis and management.
- Multiplex autoantibody arrays offer a high-throughput approach to screen for multiple autoantibodies simultaneously.
Purpose of the Study:
- To investigate the utility of multiplex autoantibody arrays in identifying novel biomarker signatures in children with autoimmune diseases, particularly polyautoimmunity.
- To compare autoantibody profiles between children with single autoimmune diseases and those with polyautoimmunity.
Main Methods:
- Plasma samples from 114 children (≤18 years) were analyzed using a microarray detecting 120 autoantigens.
- Immunoglobulin G (IgG) and Immunoglobulin A (IgA) autoantibodies were assessed.
- Patients were classified into groups: celiac disease (CeD), juvenile idiopathic arthritis, polyautoimmunity, and controls.
Main Results:
- Children with polyautoimmunity exhibited higher levels of specific autoantibodies compared to other groups.
- Elevated H/K ATPase IgA and IgG, and MDA5 IgG were observed in children with both CeD and polyautoimmunity compared to CeD alone.
- The study identified distinct autoantibody profiles associated with polyautoimmunity.
Conclusions:
- Multiplex autoantibody arrays are valuable tools for identifying known and potentially novel disease-antigens in pediatric autoimmune diseases.
- Further research is needed to explore the role of H/K ATPase autoantibodies in monitoring celiac disease patients.
- This approach can aid in understanding the complex immunopathology of polyautoimmunity in children.
Objective:
To determine if multiplex autoantibody arrays can identify novel biomarker signatures in children with one or multiple autoimmune diseases (polyautoimmunity).
Methods:
Plasma collected from children (18 years or younger) in the Boston Children's Hospital Precision Link Biobank for Health Discovery between January 2007 and June 2021 was analyzed using a microarray with 120 autoantigens associated with various autoimmune diseases to assess for both immunoglobulin G (IgG) and A (IgA) autoantibodies. To determine if disease-specific, we binary classified those with polyautoimmunity and the most common autoimmune diseases in our cohort (autoimmune thyroid disease, type 1 diabetes, or celiac disease [CeD]). For each comparison within and between groups, the autoantibody intensity was releveled to the control and a linear model was fit.
Results:
Plasma was analyzed from 114 children with either CeD (n = 31), juvenile idiopathic arthritis (n = 20), polyautoimmunity (n = 31), or no autoimmune disease (n = 32). Overall, children with polyautoimmunity had higher levels of specific autoantibodies relative to the other groups. Children with CeD and polyautoimmunity expressed higher levels of H/K ATPase IgA and IgG and MDA5 IgG compared to those with CeD alone.
Conclusions:
Use of multiplex antigen arrays in patients with and without polyautoimmunity is a valuable tool to identify known and potentially novel disease-antigens. Further study is needed to determine the role of H/K ATPase autoantibodies in monitoring of CeD patients.
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