Predicting Autoimmunity Development in 22q11.2DS

Autoimmunity is a known complication of the 22q11.2 deletion syndrome (22q11.2DS) but predictive biomarkers for risk have not been identified. In most cases, autoimmunity develops 8 years after 22q11.2DS diagnosis. We sought to determine if immune biomarkers during early childhood could predict autoimmunity later in life. Retrospective chart investigation of patients with 22q11.2 from Duke University from 2008 to 2019. Only participants who had 22q11.2 deletion by FISH or microarray were evaluated. Fisher & Mann Whitney U tests were used for statistical analysis comparing 22q11.2DS patients with and without autoimmune disease. Study was IRB approved. Seventy-one patients with 22q11.2DS were identified, and 19 of 71 (26.8%) had a physician diagnosis of autoimmune disease. The most common autoimmune diagnoses were cytopenias followed by psoriasis and juvenile arthritis. Prevalence of an autoimmune diagnosis was not significantly different for those with complete versus partial DiGeorge Syndrome. The presence of hypoparathyroidism (OR 3.5, p=0.03) and allergic rhinitis (OR 0.3, p=0.03) significantly correlated with autoimmunity. T cell lymphopenia at 22q11.2 diagnosis (median age 4 years) was correlated with autoimmunity (p=0.01). Multiple T cell subsets were independently associated with autoimmunity including CD4 (p=0.01), CD8 (p=0.01), and naïve CD4 T cells (p=0.01). NK cell numbers, B cell numbers, PHA response, vaccine responses, and size of 22q11.2 deletion were not correlative with autoimmunity. 22q11.2DS patients with hypoparathyroidism and T cell lymphopenia were associated with a higher risk of autoimmune disease. This study indicates that immune biomarkers present in early childhood may predict risk for autoimmunity later in life.