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

Abstract

Background: Neurological disorders have been identified to be a common extraglandular manifestation of Sjogren's 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 degen-eration 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.

Differentiating central nervous system demyelinating disorders: The role of clinical, laboratory, imaging characteristics and peripheral blood type I interferon activity

“…Of note, lupus and primary SS were the prevailing SAD diagnoses detected in our cohort, compatible with previous observations (Delalande et al, 2004;Bertsias and Boumpas, 2010;Massara et al, 2010;Unterman et al, 2011;Borowoy et al, 2012;Schwartz et al, 2019) and anti-Ro/SSA were the predominant reactivity among patients with SAD. This is in accord with previous studies on lupus and primary SS also highlighting the role of anti-Ro/SSA as a marker of neuropsychiatric involvement (Alexander et al, 1994;Mikdashi and Handwerger, 2004;Morreale et al, 2014;Fan et al, 2021;Tetsuka et al, 2021) and disease activity in the setting of NMOSD (Lin et al, 2022).…”

A Case of Superficial Siderosis with Elevated Anti-Ro/SSA Antibody

“… 3 ) Both target three cellular proteins, namely, Ro52/TRIM21, Ro60, and La48, which are classified based on their molecular weight. 4 ) Tetsuka et al collectively reported on 14 patients previously diagnosed with SjS who also developed cerebellar degeneration. 4 ) In all patients, serum anti-Ro/SSA antibodies were positive.…”

Anti-Ro52 antibody is a risk factor for depression and anxiety in patients with connective tissue diseases: an observational, single-center, cross-sectional study

“…The role of anti-Ro52 antibody in the pathogenesis of depression and anxiety is still unclear. A recent study revealed the presence of anti-Ro52 antibodies in the CSF of an SS patient with cerebellar degeneration, and animal experiments showed that Ro52/TRIM21 expression was present throughout murine brains, including the hippocampus, cerebral cortex and cerebellum, indicating that anti-Ro/SSA antibodies were likely responsible for cerebellar degeneration in patients with SS [32]. Another study reported that intrathecal production of anti-52-kD SSA antibodies was observed in patients with SS with CNS involvement, suggesting that CSF anti-52-kD SSA might serve as a biomarker for SS-related CNS disease [33], including mental disorders such as depression and anxiety.…”