Cytokine profiles in myasthenia gravis subgroups and the lack of any effect of immunosuppression

Abstract

Introduction/Aims: Myasthenia gravis (MG) is a clinically and immunologically heterogeneous autoimmune disease and there is little known about the differential effects of cytokines in disease subgroups. This study aimed to compare serum cytokine profiles across distinct MG subgroups, including early-onset MG (EOMG), late-onset MG (LOMG), muscle-specific kinase antibody-positive MG (MuSK-MG), thymoma-associated MG (TAMG), and healthy controls (HC) in order to distinguish and determine relatively specific targets for the disease subgroups. Methods: Serum samples from 22 EOMG, 23 LOMG, 17 MuSK-MG, 25 TAMG patients, and 25 HC were analyzed for a panel of cytokines involved in T and B cell interactions using multiplex bead-based immunoassays and ELISA. Additionally, paired serum samples of the same patients before and after immunosuppressive therapy were evaluated in a subset of patients. Results: IL-17A, IL-4, IFN-gamma, IL-21, and IL-9 were significantly elevated in EOMG and MuSK-MG groups, whereas IL-17F, IL-37, IL-2, TNF-alpha, and IL-13 were higher in EOMG only compared with HC. Increased levels of IL-6 in MuSK-MG and IL-37 in EOMG were found in these subtypes. In contrast, LOMG and TAMG patients showed limited cytokine alterations, with significant increases only in IL-21 in LOMG and IL-17A in TAMG. Immunosuppressive therapy did not significantly alter serum cytokine concentrations. Discussion: The findings reveal heterogeneous cytokine signatures among diverse MG subgroups, separating EOMG and MuSK-MG from TAMG and LOMG with some similarities and highlighting the impact of age and thymoma presence on immune responses. This assessment of disease subgroups has provided a broader understanding of the cytokines in MG.