Ab0804 Anti-Ro52 Autoantibodies Predict Sjögren’s Syndrome in Primary Biliary Cholangitis

Background: Primary biliary cholangitis (PBC) is an autoimmune liver disease with cholestasis, a risk of progression to cirrhosis and end-stage liver disease.1 A common comorbidity is the autoimmune, systemic connective tissue disease Sjögren's syndrome, which affects the exocrine glands of the eyes and mouth and causes fatigue and arthralgia. Anti-Ro52/TRIM21 autoantibodies (from now called anti-Ro52) are common in Sjögren's syndrome (SS) but are also seen in PBC.2,3 They are targeted against the intracellular receptor TRIM21, which consists of 4 domains: PRY/SPRY, Coiled-Coil, B-box, and RING.4 Patients with SS exhibit antibodies against three of the individual domains.5 Objectives: We examined a cohort of Danish PBC patients for autoantibodies against TRIM21 and its individual domains. Secondly, we aimed to establish correlations between cohort demographics, comorbidities, and sicca symptoms and the presence of anti-Ro52. Methods: We investigated a cohort of 236 PBC patients. At inclusion, biochemical status and comorbidity data were registered alongside plasma samples. Patients completed the health-related quality of life questionnaire, PBC-40, in which they were asked about the severity of sicca symptoms. Antibodies against TRIM21 and its individual domains in plasma samples were analysed by ELISA. Binomial regression determined the risk rate between variables and antibody positivity. Results: Forty plasma samples (16.9%) were positive for anti-Ro52. Twenty-three samples (9.7%) were positive for antibodies against the RING domain, 12 against the PRY/SPRY domain and ten against the Coiled-Coil domain (4.2%). Unadjusted regression analysis showed that IgG > 15mg/ml and SS increased the risk of anti-TRIM21 autoantibodies and all domain antibodies. The symptom of dry mouth also increased the risk of being positive for anti-Ro52 (RR=2.46 95%CI 1.21-1.26, p=0.023). When stratifying for SS, the RR between increased IgG, anti-Ro52, and anti-Coiled-Coil autoantibodies remained. A similar trend for increased risk between dry mouth and anti-Ro52 also remained (RR=2.02 95%CI 0.96-4.09, p=0.084). Post-hoc analysis of the cohort showed that two of the 40 antibody-positive patients had additionally been diagnosed with SS, three and five years, respectively, after inclusion in the PBC cohort. Eighteen had yet to be referred for investigation by rheumatologists, and ten patients were lost to follow-up. Conclusion: We report a 16.9% positivity of anti-Ro52 in a Danish PBC cohort. Furthermore, we observed a correlation between increased IgG (>15mg/ml), SS and dry mouth and having anti-Ro52. Stratification of SS patients shows that they drive the correlation, but as the risk between dry mouth and anti-ro52 remains, we argue that some SS patients are undiagnosed in the PBC cohort. We recommend that all PBC patients are tested for anti-Ro52 and, if positive, referred for examination by a rheumatologist. This should be done to avoid diagnostic delays, facilitate optimal treatment, and educate patients suffering from SS. REFERENCES: 1 Lleo, A., Leung, P. S. C., Hirschfield, G. M. & Gershwin, E. M. The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review. Semin Liver Dis40, 34-48 (2020). https://doi.org:10.1055/s-0039-1697617 2 Granito, A. et al. Antibodies to SS-A/Ro-52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis. Aliment Pharmacol Ther26, 831-838 (2007). https://doi.org:10.1111/j.1365-2036.2007.03433.x 3 Fox, R. I. Sjögren's syndrome. Lancet366, 321-331 (2005). https://doi.org:10.1016/s0140-6736(05)66990-5 4 Jones, E. L., Laidlaw, S. M. & Dustin, L. B. TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease. Front Immunol12, 738473 (2021). https://doi.org:10.3389/fimmu.2021.738473 5 Dahl, M. L. N. et al. Validation of an indirect ELISA assay for assessment of autoantibodies against full-length TRIM21 and its individual domains. Scand J Clin Lab Invest83, 309-317 (2023). https://doi.org:10.1080/00365513.2023.2221862 Acknowledgements: NIL. Disclosure of Interests: Marie N Dahl: None declared, Lars L Bossen: None declared, Trine-Line Korsholm: None declared, Jakob H Mikkelsen: None declared, Malene Hvid: None declared, Ayad Babaee: None declared, Christian B F Andersen: None declared, Henning Grønbæk Data Monitoring Committee at CAMURUS., Research grants from Intercept, ARLA Food for Health., Bent Deleuran: None declared.