Reduction of Total Brain and Cerebellum Volumes Associated With Neuronal Autoantibodies in Patients With APECED

Context: In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), autoantibodies (AutoAbs) labeling brain neurons were reported; conversely, brain MRI alterations associated with these AutoAbs were never reported.Objectives: To describe brain alterations in APECED and to correlate them with AutoAbs against glutamic acid decarboxylase (GAD)-, tyrosine hydroxylase (TH)-, and 5-tryptophan hydroxylase (5-HT)- neurons. Design and participants: Fourteen Sardinian APECED patients and age-matched control subjects were recruited for MRI analysis and blood sampling to detect AutoAbs to GAD-, TH-, and 5-HT- neurons using rat brain sections. The majority of patients (n=12) were investigated for AutoAbs a decade ago and 7/12 were positive for AutoAbs to GAD and TH neurons. Main outcomes: APECED patients had smaller cerebellum and gray matter volumes, with a ventricular enlargement and a total liquor increase, compared to controls (p<0.01). In 11/14 patients, brain abnormalities were associated with AutoAbs to GAD and/or TH neurons (titer 1:100–15000), that had persisted for 10 years in 7/11 patients. AutoAbs to 5-HT neurons were revealed in all patients with AutoAbs to TH neurons. A decrease in whole brain and cerebellum volumes (p=0.028) was associated with AutoAbs to GAD neurons while a liquor increase with AutoAbs to GAD- and TH/5-HT neurons (p<0.05). HLA alleles did not appear to be involved in neuronal autoimmunity. Conclusions: For the first time, brain alterations together with neuronal AutoAbs were observed in 78.6% Sardinian APECED patients, suggesting a brain autoimmune reaction. Prolonged clinical follow-up must be conducted for the possible appearance of clinical neurological consequences. We revealed that APECED patients had smaller cerebellum and gray matter volumes, with a ventricular enlargement and a total liquor increase, all associated (in 11/14) with brain neuron AutoAbs.