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Tripartite motif-containing protein 21 (TRIM21)/Ro52 is an immunoglobulin receptor that together with Ro60 makes up Sjögren’s syndrome-antigen A (SSA). A 60%–80% of patients with primary Sjögren’s syndrome (pSS) have anti-SSA autoantibodies and they form part of the pSS diagnosis. TRIM21 is a cytosolic Fc-receptor that mediates neutralisation of opsonised viruses and other particles, acting as a last line of defence against viruses that are recognised by antibodies but still manage to penetrate the cell membrane.1 In addition, TRIM21 regulates type I interferon (IFN) responses by mediating either stabilisation or degradation of IFN regulatory factors.1 2 Uniquely, it has a very broad antibody specificity and recognises IgA, IgG and IgM antibodies with high affinity, allowing TRIM21 to be effective against a large range of viruses.3 Alternatively, TRIM21 can be triggered by immune complexes containing non-viral particles such as cellular debris or nucleic acids,4 leading to rapid production of pro-inflammatory mediators including type I IFNs.2 Interestingly, mice immunised with TRIM21 develop anti-TRIM21 autoantibodies and salivary gland inflammation, while transfer of serum from anti-TRIM21-positive mice to naïve mice induces salivary gland dysfunction,5 suggesting a direct link between anti-TRIM21 autoantibodies and induction of Sjögren’s-like symptoms.
Considering the relevance of TRIM21 as autoantigen in pSS and its role in regulating IFN signalling, we here investigated its expression in the major type I IFN-producing immune cells, plasmacytoid dendritic cells (pDCs) and monocytes, from patients with pSS. In addition, we investigated TRIM21 expression in salivary gland tissue. For pDCs and salivary gland tissues, RNA sequencing and analysis were performed separately as previously described.6 7 For monocytes, TRIM21 expression was assessed using quantitative PCR (online supplementary methods) We observed increased mRNA expression of TRIM21 in purified pDCs from patients with pSS compared to both healthy controls and patients with non-Sjögren’s sicca …
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