The Three Sisters of Fate in Multiple Sclerosis: Klotho (Clotho), Fibroblast Growth Factor-23 (Lachesis), and Vitamin D (Atropos)

Abstract

Background: The klotho (Klt)-fibroblast growth factor-23 (FGF-23)-vitamin D axis is the main component of calcium (Ca) and phosphorus (P) metabolisms; on the contrary, it is also secreted from the choroid plexus (CP). Purpose: This study is aimed at evaluating serum soluble Klt (sKlt), FGF-23, and 25-(OH)-vitamin D levels in multiple sclerosis (MS) patients. Methods: Thirty-two relapsing-remitting MS patients (11 males and 21 females; mean age 38.3 years) and 31 age-sex matched healthy controls (12 males and 19 females; median age 38.5 years) were included in this study. All patients were diagnosed with MS according to the criteria of McDonald. Results: Serum sKlt, FGF-23, and P levels were significantly higher in MS patients compared to the control group (p < 0.01, p < 0.01, and p = 0.02, respectively). Serum 25-(OH)-vitamin D and Ca levels were significantly lower in MS patients (p < 0.01 and p = 0.04, respectively). Conclusion: Klt, which is secreted from CP, could be a response to the inflammatory condition in MS. Elevated FGF-23 levels suppress 1α-hydroxylase and upregulates 24α-hydroxylase, which results in a decrease in 1,25-(OH)₂D₃ levels. Thus, the neuroprotective and immunomodulatory effects of vitamin D might not be seen in MS patients.