Neurological Autoimmunity Associated With Homer-3 Antibody: A Case Series From China

Abstract

Background and objective: To present 6 new cases with Homer-3 antibodies that expand their clinical spectra and to evaluate the effect of immunotherapy.

Methods: Patients with suspected autoimmune cerebellar disorder were tested for rare autoimmune cerebellar ataxia (ACA) antibodies (anti-Tr(DNER)/Zic4/ITPR1/Homer-3/NCDN/PKCγ/PCA-2/AP3B2/mGluR1/ATP1A3 antibodies) using both cell-based and tissue-based assays. Patients with positive serum or CSF results who were diagnosed with ACA were registered and followed up. This study reports and analyzes cases with Homer-3 antibodies.

Results: Of the serum and CSF samples of 750 patients tested, 6 were positive for Homer-3 antibodies. All manifested subacute or insidious-onset cerebellar ataxia. Furthermore, 2 patients each exhibited encephalopathy, myeloradiculopathy, REM sleep behavior disorder, and autonomic dysfunction. Brain magnetic resonance images were normal (n = 1) or revealed cerebellar atrophy (n = 1), cerebellum and pons atrophy with the hot cross bun sign (n = 2), and bilateral cerebral abnormalities (n = 2). Definite leukocytosis was identified in the CSF of 2 patients, protein concentration elevation was observed in the CSF of 1 patient, and oligoclonal bands were present in 2 patients. All patients received immunotherapy, including corticosteroid, IV immunoglobulin, plasma exchange, and mycophenolate mofetil, after which the residual disability was still severe (modified Rankin Scale score ≥3 at the last follow-up in 4 patients and final Scale for the Assessment and Rating of Ataxia scores of 12-29), although 4 patients partially improved and 1 patient stabilized. The remaining 1 patient continued to deteriorate after repeated immunotherapy. Two patients relapsed.

Discussion: Disorders associated with Homer-3 antibody can mimic multiple system atrophy with cerebellar features in both clinical and radiologic aspects. Accurate identification of autoimmune-mediated cases is critical. Timely, comprehensive immunotherapy is warranted, given the possibility of long-term clinical benefit.

Figure 1. Brain MRI Findings in Patients 1, 2, and 6

(A) Cerebellum atrophy (patient 1) (B) fluid-attenuated inversion recovery and diffusion weighted imaging hyperintensity in bilateral frontal and parietal cortex (patient 6), and (C) cerebellum and pons atrophy with hot cross bun sign (patient 2).

Figure 2. Reactivity of Patients' Serum With Monkey Cerebellum and HEK293 Cells Transfected With Homer-3

(A) Tissue-based assay of patient serum using monkey cerebellum tissue sections showing immunofluorescence of Purkinje cell cytoplasm and dendrites (×200) and (B) serum Homer-3 antibody detected by cell-based assay (fixed HEK293 cells, ×200).