Background and Aims

Autoimmune cerebellar ataxias (ACA) comprise a rare group of disorders frequently associated with neuronal antibodies, which are considered excellent biomarkers of autoimmunity, and in some cases, of cancer. Herein, we aim to define the clinical features of ACA associated with antibodies targeting the regulator of G-protein signaling 8 (RGS8-Abs) and antibody characteristics of 4 patients. Histopathological features of the tumours were available for two patients.

Methods

Indirect immunofluorescence assays on rat brain-tissue, in-house cell-based assay and a customised line blot were used to screen patients with ACA. Antibody characterisation (titers, IgG subclass) were performed with cell-based assays. To assess RGS8-Abs specificity, we tested the serum and CSF of a control cohort including 128 autoimmune encephalitis, 83 ACA, and 165 patients with neurodegenerative disorders.

Results

Four patients with subacute ACA and an underlying lymphoma presented high titers of IgG1 RGS8-Abs in serum and CSF, while none in the control cohort (Figure 1). Three patients had a Hodgkin’s lymphoma, although two were a rare type termed nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL), and another had a B-cell lymphoma of the stomach. All patients were treated with chemotherapy and immunotherapy leading to a mild clinical improvement but all remained moderately disabled.

Figure 1A: Rat brain-tissue indirect immunofluorescence with patient 1’ CSF. Figure 1B: Cell-based assays with RGS8-transfected HEK293 with patient 1’CSF.

Conclusions

Our findings suggest RGS8-Abs to be a specific biomarker of paraneoplastic ACA and Hodgkin’s lymphomas. Despite being a rare variant of lymphomas, NLPHL may represent a hallmark of RGS-8 related ACA.