Investigating the role of tripartite motif containing-21 and interleukin-6 in pro-Inflammatory symptom-associated heterogeneity within primary Sjögren's syndrome.

Background and objectives: In Primary Sjögren's Syndrome (pSS) clinical heterogeneity is a challenge to both treatment and disease understanding. Variations in symptoms may be driven by different underlying biological pathways. Tripartite motif containing-21 (TRIM21) and interleukin-6 (IL-6) have been implicated in autoimmunity and inflammation, with links to chronic interferon activity. We assess the levels of TRIM21 and IL-6 in the context of anti-Ro autoantibody status, and in different symptom-based pSS subgroups we have previously described, to explore whether they may contribute to the clinical heterogeneity in pSS.

Methods: We measured serum IL-6 concentrations for 193 pSS patients and 18 healthy controls, and analysed available microarray data for TRIM21 transcript expression in 184 pSS patients and 33 healthy controls. Levels of IL-6 and TRIM21 were analysed in the context of symptom-based subgroups, anti-Ro autoantibody status and symptom scores.

Results: TRIM21 and IL-6 levels were significantly raised in pSS patients compared to healthy controls. TRIM21 expression was similar between symptom-based subgroups, whilst IL-6 concentrations were significantly increased in the high symptom burden group compared to the low symptom burden group. TRIM21 levels were significantly increased in Ro+ autoantibody groups compared to Ro-, whilst IL-6 levels were similar between groups.

Conclusions: Our results suggest a potential role for IL-6 in the pathogenesis of the high symptom burden group. Increased TRIM21 transcript levels in the Ro+ group supports the hypothesis of suggests autoantibody targeting of the TRIM21 protein leading to aberrant type I interferon (IFN) production which in turn may drive further TRIM21 transcript production.