Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a common congenital primary immune deficiency that typically presents with conotruncal cardiac defects, hypocalcemia, palatal abnormalities, dysmorphic facial features, and diminished T cell numbers. In addition to increased risk of infection, increased rates of autoimmune disease have been associated with this condition. Disease progression can include neuropsychiatric symptoms. Autoimmunity has been linked to psychiatric disease in the general population and in the systemic lupus erythematosus (SLE) population. There is little known about patterns of autoantibodies in 22q11.2DS patients and whether they vary with age and neuropsychiatric symptoms.
The study population included children and adults with 22q11.2DS and healthy controls without 22q11.2DS or autoimmune disease. Plasma samples were sent to the University of Texas Southwestern Medical Center for panel IV and superpanel immunoglobulin G (IgG) and immunoglobulin M (IgM) autoantigen microarray. Normalized signal intensity was calculated for each antigen. Two-tailed Student’s t test was used for statistical analysis with Bonferroni correction for multiple hypothesis tests. R and ggplot2 were used for data analysis and heatmap creation.
Data are available for 50 autoantigens and 80 subjects: 57 patients (29 adults and 28 children) and 23 controls (15 adults and 8 children). 10 adult patients had a diagnosis of schizophrenia. Adults with 22q11.2DS and schizophrenia had significantly elevated IgM and IgG titers to 18 autoantigens compared with all adults (controls and 22q11.2DS patients without schizophrenia), including histone H3, Smith and ribonucleoprotein, centromere proteins A and B, single-stranded deoxyribonucleic acid, and myeloperoxidase. Anti-histone H1 and H2A IgG and IgM titers were significantly higher in child patients; anti-histone H2B and myosin IgM titers were also significantly higher in child patients. About half of autoantigens tested had significantly lower titers in child patients compared with child controls (26 for IgG and 23 for IgM). IgG and IgM titers to IL-6 were lower in patients than controls across all comparisons, though not all reached a level of statistical significance once adjusted.
Differences in autoantibody production in patients with 22q11.2DS may contribute to the increased rate of autoimmune disease, loss of tolerance, and neuropsychiatric symptoms seen in this population.
(a) Immunoglobulin M (IgM) autoantibodies normalized signal intensity for patients with 22q11.2 deletion syndrome and controls. (b) Immunoglobulin G (IgG) autoantibodies normalized signal intensity for patients with 22q11.2 deletion syndrome and controls.
(a) Immunoglobulin M (IgM) autoantibodies normalized signal intensity for patients with 22q11.2 deletion syndrome and controls. (b) Immunoglobulin G (IgG) autoantibodies normalized signal intensity for patients with 22q11.2 deletion syndrome and controls.
