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AbstractBackground: Anti-IL-6 autoantibodies are anti-cytokine autoantibodies that bind IL-6 and potentially modulate IL-6 signalling by neutralising its function or prolonging its circulation time. Anti-IL-6 autoantibodies have been detected in healthy individuals and patients with certain diseases, e.g. systemic sclerosis. Individuals with high levels of anti-IL-6 autoantibodies were reported to have an insufficient immune response to specific pathogens. On the other hand, elevated levels of anti-IL-6 autoantibodies were also suggested to have protective and immunomodulatory roles. Objectives: Overall, the prevalence, function, and biological significance of anti-IL-6 autoantibodies are still unclear. As IL-6 signalling is important in the pathology and treatment of idiopathic inflammatory myopathies (IIM), we explored the quantity and quality of anti-IL6 autoantibodies in IIM. Methods: After obtaining informed consent, serum samples were collected from 41 consecutive IIM patients (21 dermatomyositis, 4 polymyositis, 4 immune-mediated necrotising myopathy, 10 antisynthetase syndrome and 2 overlap syndrome patients) diagnosed at the Department of Rheumatology, University Medical Centre Ljubljana, and from 39 healthy age- and sex-matched controls. Twelve IIM patients were newly diagnosed and treatment-naive, and 29 had been previously already treated with immunomodulatory therapeutics. In all samples, serum levels of IL-6 and anti-IL-6 autoantibodies were measured using ELISA. A reporter gene cell line responsive to IL-6 was used to determine the ability of the sera to neutralise IL-6 signalling. Results: Serum levels of IL-6 were significantly higher in IIM patients, reaching a median of 19.5 pg/mL in IIM patients compared with 4 pg/mL in healthy controls (pConclusion: This study demonstrated the presence of anti-IL-6 autoantibodies in healthy individuals and their slightly decreased levels in patients with IIM, with the most significant decrease observed in patients with dermatomyositis. The capacity of IIM sera to neutralise IL-6 signalling was significantly reduced compared to HC, which is consistent with previous reports of pathologically overactive IL-6 signalling in IIM patients. The detected anti-IL-6 autoantibodies were functionally heterogeneous, as the measured concentrations did not correlate with the IL-6 neutralising level. In addition, patients with higher IL-6 neutralisation levels tended to have lower serum levels of inflammatory and muscle damage markers. These results indicate that anti-IL-6 autoantibodies may have an immunomodulatory effect by limiting IL-6 signalling and that their reduced levels in IIM may be involved in disease development or progression. REFERENCES: 1 Bloomfield, M., Parackova, Z., Cabelova, T., Pospisilova, I., Kabicek, P., Houstkova, H., & Sediva, A. (2019). Anti-IL6 Autoantibodies in an Infant With CRP-Less Septic Shock. Front Immunol, 10, 2629. https://doi.org/10.3389/fimmu.2019.02629. 2 Hansen, M. B., Svenson, M., Diamant, M., & Bendtzen, K. (1991). Anti-interleukin-6 antibodies in normal human serum. Scand J Immunol, 33(6), 777-781. https://doi.org/10.1111/j.1365-3083.1991.tb02552.x. 3 Takemura, H., Suzuki, H., Yoshizaki, K., Ogata, A., Yuhara, T., Akama, T., Yamane, K., & Kashiwagi, H. (1992). Anti-interleukin-6 autoantibodies in rheumatic diseases. Increased frequency in the sera of patients with systemic sclerosis. Arthritis Rheum, 35(8), 940-943. https://doi.org/10.1002/art.1780350814. Acknowledgements: This work was supported by the Slovenian Research Agency (grants P3-0314 and P3-0043). Disclosure of Interests: None declared. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.
Srpčič et al. (Sun,) studied this question.