Abstract: Objective: Alpha-Klotho protein (A-Klotho) is an essential component of endocrine fibroblast growth factor receptor complexes that governs multiple metabolic processes including aging-related disorders, diabetes, cancer, arteriosclerosis, and chronic kidney disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect almost any organ in the body and in which multiple pathophysiological abnormalities are observed. In the present work, our objective was to study whether the serum levels of ?-Klotho differ between patients with SLE and controls, and how this protein is related to the clinical and laboratory characteristics of the disease. Methods: Cross-sectional study that included 364 women, 195 of them diagnosed with SLE and 169 sex- and age-matched controls. Circulating A-Klotho was analysed in SLE patients and controls. A multivariable analysis was performed to assess whether A-Klotho differs between patients and controls, and to study its relationship with SLE features. Results: No differences were found in A-Klotho levels between SLE patients and controls, both in univariable and multivariable analyses. Disease-related data like SLE duration, acute phase reactants, activity, severity and damage indices, and autoantibodies profile were not significantly associated with serum levels of A-Klotho. However, the use of prednisone and the presence of musculoskeletal manifestations were significantly related to higher A-Klotho serum levels. Conclusion: A-Klotho protein serum levels do not differ between patients with SLE and controls. Nevertheless, SLE patients taking prednisone or those with musculoskeletal manifestations show significantly higher circulating levels of A-Klotho.

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