Abstract Details

Varied neurological phenotypes have been associated with ANNA1 autoimmunity. Most ANNA1 IgG seropositive patients are older adults (>50 years of age) often associated with small cell lung carcinoma. However, data on clinical and oncologic profiles of young adults and pediatric patients with this antibody are limited.

To describe the phenotypic, oncological associations and outcomes across different age groups in patients with ANNA1 (anti-Hu) autoimmunity.

A retrospective review of patients with ANNA1-IgG in serum/CSF (positive by tissue-immunofluorescence and western blot/immunodot) between 1/1/2001 and 12/31/2019 was performed. Patients were classified into three different groups based on age of symptom onset: >45(older adults), 18-45(young adults) and <18 years(pediatric), respectively.

Of 122 patients, 81 (66%), 20 (16%) and 21(17%) patients belonged to older adults, young adults, and pediatric groups, respectively. Smoking, lung cancer and neuromuscular manifestations were more common in older adults (P<.001), while limbic encephalitis and neuroblastoma was more common in pediatric patients (P<.005). In contrast to children and older adults, 75% of young adults did not have cancer identified although they phenotypically resembled the older adults. Co-existent high and intermediate risk neural antibodies were seen in 10 (8%) older adults, predominantly with underlying lung cancer (80%). Proportion of patients with favorable response to immunotherapy was 20%, 30% and 52% among older adults, young adults, and pediatric groups, respectively. At final follow up, mortality was seen in 33% patients predominantly in older adults (45%) and none in pediatric group.

Despite bearing resemblance to older adults in neurologic phenotype and clinical outcome, young adults with ANNA1 autoimmunity rarely had an underlying cancer. On the contrary, pediatric patients frequently presented with limbic encephalitis with/without neuroblastoma, and often responded favorably to immunotherapy. Recognizing the spectrum of ANNA1 autoimmunity amongst the different age groups will enable appropriate oncological screening and administration of immunotherapies.