A new case of Homer-3 autoimmunity has been described, expanding the still limited body of knowledge about this rare autoimmune cerebellar disorder. The case was reported in the Journal of Neuroimmunology in a collaboration between Euroimmun and Mayo Clinic (USA).
What’s known so far
To date, only 15 cases of Homer-3 autoantibody-associated disease have been described in the literature. The clinical phenotype in these reports is predominantly subacute cerebellar ataxia, in some cases accompanied by cognitive impairment, REM sleep behaviour disorder, seizures, myeloradiculopathy, radiculoneuropathy or psychosis. Notably, only one patient had cancer, suggesting that Homer-3 autoimmunity has limited paraneoplastic association.
Homer-3 is a postsynaptic cytoplasmic protein expressed mainly in cerebellar Purkinje cells. Given its cytoplasmic target, Homer-3 IgG is not considered directly pathogenic. Instead, it likely serves as a biomarker of a T cell-mediated immune response. In indirect immunofluorescence assay (IFA), anti-Homer-3 autoantibodies produce a characteristic staining of the cerebellar molecular layer known as the “medusa head” pattern. Similar staining is observed with other autoantibodies, including ITPR1 IgG and GRAF1 IgG, underscoring the need for antigen-specific confirmatory testing.
Characteristics of new case
The patient described in the current report presented with insidious-onset cerebellar ataxia and mild cognitive impairment and was initially diagnosed with parkinsonism. As part of a further workup for ataxia, she was tested for neural autoantibodies.
Tissue-based IFA of both cerebrospinal fluid (CSF) and serum revealed the “medusa head” pattern in the cerebellum. Additional staining was observed in the hippocampus, with lower intensity reactivity in the cerebral cortex, thalamus and basal ganglia. Protein microarray analysis identified Homer-3 as the target antigen. The finding was confirmed by robust positivity in a Homer-3-specific line blot in both serum and CSF. The patient was treated with immunosuppressives but showed only minor improvement.
Additional insights into Homer-3 autoimmunity
To explore the broader frequency of Homer-3 autoimmunity, two cohorts were screened. Among 51 samples showing a “medusa head” pattern in IFA but negative for ITPR1/GRAF-1 IgG, one serum tested positive for Homer-3 IgG by line blot. In a second cohort of 258 samples with diverse unclassified synaptic staining pattens in IFA, one serum was positive for Homer-3 on protein microarray (line blot confirmation not available).
Overall, the new case reinforces the predominance of a cerebellar phenotype in Homer-3 autoimmunity. The limited therapeutic response is consistent with previous cases and is likely due to irreversible loss of Purkinje cells at an early stage of disease. This aspect highlights the need for early consideration of autoimmune aetiologies in cases of cerebellar ataxia. In future studies, Homer-3 autoimmunity could be detected by combining tissue-based IFA of serum and CSF with confirmatory antigen-specific assays such as Homer-3 immunoblot or cell-based assay.
Read the full paper here: Anissian D, et al. A case of Homer-3 IgG cerebellar ataxia & literature review of 15 reported cases. J Neuroimmunol. 412:578846 (2026).
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