Rho GTPase Activating Protein 26 (ARHGAP26)-Igg Autoimmunity: Frequency and Clinical Associations (P3.346)

Objectives: To report the frequency, clinical characteristics, immunotherapy response and oncological associations of a newly recognized neuronal autoantibody, ARHGAP26-IgG.Background: To date, 4 patients with ARHGAP26-IgG have been reported: 3 had cerebellar ataxia (1 with ovarian cancer) and the fourth patient had limbic encephalitis with coexisting voltage-gated Kv1-potassium channel-complex antibodies. Design/Methods: In the course of service evaluation of patients’ sera for paraneoplastic autoantibodies, between 2007 and 2015, IgGs in 100 were classified (by mouse tissue-based indirect-immunofluorescence assay) as yielding a “Medusa head-type” pattern of cerebellar staining. These sera were evaluated for the presence of ARHGAP26-IgG using a transfected cell-based assay (Euroimmun, Germany).Results: ARHGAP26-IgG was detected in 13 patients’ sera: 62[percnt] were male; median age at neurological symptom onset was 61 years (range 19-76). Three clinical subgroups were observed among 12 patients with available clinical information: 1] isolated cerebellar ataxia (5), 2] isolated peripheral neuropathy (3) and 3] cerebellar ataxia “plus” other neurological manifestations (4); peripheral neuropathy in 2, pseudobulbar affect in 1 and cognitive decline in 1. MRI brain, available in 3 patients with cerebellar ataxia showed cerebellar atrophy in 3; 1 additionally had brainstem atrophy. Follow-up information concerning neoplastic associations was limited: one patient had squamous-cell carcinoma in a cervical lymph node (primary unknown); two had increased FDG uptake on PET-CT body imaging (mediastinal lymph nodes [1]; lingual tonsils/inguinal lymph nodes [1]). None of 8 patients who received immunotherapy reported improvement. The frequency of ARHGAP26-IgG detection in the 12-month-period 2014-2015 was 0.004[percnt] (2 among 52,000 sera evaluated), higher than the 0.002[percnt] detection frequency for PCA-Tr (Delta/notch-like epidermal growth factor-related receptor), but lower than the 0.015[percnt] frequency of another Medusa head-type autoantibody (ITPR1-IgG).Conclusion: Common manifestations of ARHGAP26 autoimmunity include subacute ataxia/ cerebellar degeneration and peripheral neuropathy. Cases in this series responded poorly to immunotherapy. Disclosure: Dr. Alfugham has nothing to disclose. Dr. Lennon has received research support from the National Institutes of Health. Dr. Komorowski has received personal compensation for activities with EuroImmun AG as an employee. Dr. Probst has nothing to disclose. Dr. Pittock has received (royalty or license fee or contractual rights) payments from Peripherin-Specific Autoantibodies as a Marker for Neurological and Endocrinological Disease.