From genes to environment: A life-course approach to prevent pediatric autoimmune diseases

Table 3 Periodic antibody screening for early detection of autoimmune diseases in high-risk children

Autoimmune disease	High-risk population	Key antibodies for screening	Interpretation	Potential early intervention
Established standard
T1DM	Children with a first-degree relative with T1DM or high-risk HLA genotypes	GAD65, IA-2, insulin autoantibodies, ZnT8	High evidence quality: ≥ 2 positive antibodies = high risk of progression to diabetes	Close monitoring, enrollment in prevention trials (e.g., teplizumab for stage 2), lifestyle/dietary counseling
Celiac disease	Children with a first-degree relative with celiac disease, or high-risk HLA (DQ2/DQ8)	Anti-tTG (IgA), EMA, deamidated gliadin peptide antibodies	High evidence quality: Positive serology suggests a high likelihood of disease and villous atrophy even in asymptomatic children	Early dietary intervention (gluten-free diet) to prevent growth failure and nutritional deficiencies
Autoimmune thyroid disease	Children with a family history of thyroid disease, or other autoimmune disorders (e.g., T1DM, down syndrome, turner syndrome)	Anti-thyroid peroxidase, anti-thyroglobulin	Moderate-high evidence quality: Antibody positivity often precedes clinical hypothyroidism/thyroiditis	Monitoring thyroid function, early initiation of hormone therapy if indicated
Emerging/research
SLE (research/experimental use)	Offspring of mothers with SLE or anti-Ro/SSA positivity	ANA, anti-dsDNA, anti-Ro/SSA. Antibodies may appear before clinical disease	Lower specificity: ANA is highly sensitive but lacks specificity for prediction in asymptomatic children	Serial monitoring; counseling on sun protection and infection triggers; hydroxychloroquine in specific research cohorts
JIA	Children with a strong family history of JIA or early-onset uveitis	ANA, RF, anti-CCP, HLA-B27	Lower evidence quality: ANA is primarily a marker for uveitis risk; RF/anti-CCP are predictive of severe polyarticular course but not disease onset	Baseline ophthalmologic exam for uveitis; prompt referral upon subtle musculoskeletal symptoms

The table summarizes recommended periodic antibody screening for the early detection of autoimmune diseases in children with elevated genetic, familial, or clinical risk. Early serologic positivity - often emerging months to years before overt disease - provides a window for close monitoring, anticipatory guidance, and, in selected cases, preventive intervention. The table outlines high-risk populations, key disease-specific autoantibodies used for screening, typical interpretation thresholds, and corresponding early actions. Note the disparity in evidence quality: Strategies for type 1 diabetes mellitus and celiac disease are supported by standardized international guidelines and highly specific biomarkers. In contrast, screening for systemic lupus erythematosus and juvenile idiopathic arthritis remains less standardized and primarily exploratory, as markers like antinuclear antibodies lack the specificity to predict disease onset in asymptomatic pediatric cohorts without high-risk familial contexts. These recommendations support proactive surveillance while acknowledging that clinical implementation for emerging protocols should be personalized and cautious. T1DM: Type 1 diabetes mellitus; HLA: Human leukocyte antigen; GAD: Glutamic acid decarboxylase 65; IA-2: Insulinoma-associated antigen 2; ZnT8: Zinc transporter 8; tTG: Tissue transglutaminase; Ig: Immunoglobulin; EMA: Endomysial antibodies; SLE: Systemic lupus erythematosus; Ro/SSA: Ro/Sjögren syndrome-related antigen A; ANA: Antinuclear antibodies; dsDNA: Double-stranded DNA; RF: Rheumatoid factor; CCP: Anti-cyclic citrullinated peptide.