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Published on: September 15, 2016
Determination of pediatric reference limits for 10 commonly measured autoantibodies
Lusia Sepiashvili1,2,3, Mary Kathryn Bohn1,2, Alexandra Hall1
1Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Insights
This study established pediatric reference limits for 10 autoimmune disease markers in healthy children and adolescents. These new reference intervals aid in accurate diagnosis and clinical decisions for pediatric autoimmune conditions.
Area of Science:
- Pediatric Autoimmunity
- Clinical Laboratory Medicine
- Immunoserology
Background:
- Accurate interpretation of autoimmune disease markers in children requires specific pediatric reference intervals.
- The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) aims to fill this gap by establishing robust pediatric reference data.
- Existing reference ranges are often extrapolated from adult data, potentially leading to misinterpretation in pediatric populations.
Purpose of the Study:
- To establish pediatric reference limits for 10 common autoimmune disease markers.
- To support accurate interpretation and clinical decision-making for pediatric autoimmune conditions.
- To provide a foundation for improved laboratory assessment in pediatric patients.
Main Methods:
- Recruited 123 healthy children and adolescents (aged 1-19) for the CALIPER study.
- Performed serum autoantibody testing using the BIO-FLASH analyzer for 10 specific markers (e.g., anti-dsDNA IgG, anti-MPO IgG, anti-tTG IgA).
- Calculated pediatric reference limits (95th, 97.5th, 99th percentiles) using non-parametric methods per CLSI guidelines.
Main Results:
- Established pediatric reference limits and 90% confidence intervals for all 10 autoantibodies.
- Identified age ranges for autoantibody interpretation, with exceptions for anti-cardiolipin IgG and anti-MPO.
- Observed a sex-specific difference in anti-tissue transglutaminase IgA (anti-tTG IgA) levels.
Conclusions:
- The established pediatric reference limits provide crucial data for the interpretation of autoimmune markers in children.
- These findings will enhance laboratory assessment and clinical decision-making for pediatric autoimmune diseases globally.
- Utilizing these specific pediatric reference intervals on platforms like BIO-FLASH improves diagnostic accuracy.
Objectives:
The objective of this study was to establish pediatric reference limits for autoimmune disease markers in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents to support their interpretation and clinical decision making. The CALIPER is a national study of healthy children aiming to close gaps in pediatric laboratory medicine by establishing a robust database of pediatric reference intervals for pediatric disease biomarkers (caliperdatabase.org).
Methods:
Healthy children and adolescents (n=123, aged 1-19) were recruited to CALIPER with informed consent. Serum autoantibody testing conducted on the BIO-FLASH analyzer (Werfen, Barcelona, Spain) included anti-dsDNA IgG, anti-Sm IgG, anti-RNP IgG, anti-SSB/La IgG, anti-Ro60 IgG, anti-Ro52 IgG, anti-cardiolipin IgG, anti-MPO IgG, anti-PR3 IgG, and anti-tTG IgA. Pediatric reference limits representing 95th, 97.5th, and 99th percentiles were calculated using the non-parametric rank method according to Clinical Laboratory Standards Institute C28-A3 guidelines.
Results:
The proportion of samples with results above the lower limit of the analytical measuring range were: anti-cardiolipin IgG 90%, anti-dsDNA 22%, anti-Sm 13%, anti-RNP 0.8%, anti-SSB/La 0%, anti-Ro60 0%, anti-Ro52 0%, anti-MPO 25%, anti-PR3 9%, and anti-tTG IgA 28%. Pediatric reference limits and associated 90% confidence intervals were established for all 10 markers. All autoantibodies could be described by one age range except for anti-cardiolipin IgG and anti-MPO. A sex-specific difference was identified for anti-tTG IgA.
Conclusions:
Robust pediatric reference limits for 10 commonly clinically utilized autoimmune markers established herein will allow for improved laboratory assessment and clinical decision making in pediatric patients using the BIO-FLASH assay platform worldwide.
