Anti-Ro/SSA Antibodies May Be Responsible for Cerebellar Degeneration in Sjogren’s Syndrome

Syuichi Tetsuka, Tomohiro Suzuki, Tomoko Ogawa, Ritsuo Hashimoto, Hiroyuki Kato


Background: Neurological disorders have been identified to be a common extraglandular manifestation of Sjogrens syndrome (SjS). Central nervous system (CNS) symptoms appear in about 5% of patients with SjS. However, so far, only a few incidences of cerebellar degeneration have been reported, and the clinical features and pathological mechanisms associated with SjS remain to be unclear. Intramedullary production of anti-Ro/anti-SjS-related antigen A (SSA) has been observed in some patients with SjS patients who have CNS involvement, suggesting the involvement of anti- Ro/SSA antibodies as antineuronal antibodies in previous studies.

Methods: We recently treated cerebellar degeneration in a patient with SjS. We analyzed the serum and cerebrospinal fluid (CSF) in order to detect anti-Ro/SSA and anti-La/anti-SjS-related antigen B (SSB) antibodies. We also searched the literature for previous case reports to evaluate the characteristics of cerebellar degeneration in patients with SjS. First, we have studied in mouse brain tissue and examined whether the Ro/SSA (Ro52/tripartite motif protein (TRIM)21) protein was expressed in the cerebellum of mice using immunohistochemistry.

Results: Although all patients that we found in the literature review and our patient 1 were positive for anti-Ro/SSA antibodies, some patients were also negative for anti-La/SSB antibodies. Anti-Ro/SSA antibodies were observed in both serum and CSF; however, anti-Ro/SSA antibodies were negative in the CSF of patients with SjS without CNS involvement. Cerebellar atrophy was observed, and sequelae remained in the majority of patients. Autopsy findings indicated a selective loss of Purkinje cells. Ro52/TRIM21 expression was also detected throughout murine brains, including the hippocampus, cerebral cortex and cerebellum. High Ro52/TRIM21 expression was observed in the Purkinje cells.

Conclusions: We described the characteristics of cerebellar degeneration in patients with SjS and Ro52/TRIM21 expression in the Purkinje cells of murine cerebellar tissue sections. These outcomes indicate that anti-Ro/SSA antibodies were likely responsible for cerebellar degeneration in patients suffering from SjS.

J Clin Med Res. 2021;13(2):113-120


Anti-Ro/SSA antibodies; Cerebellar degeneration; Purkinje cell; Ro52/TRIM21; Sjogren’s syndrome

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