Peripheral Immune Profile Alterations in Treatment-Naïve Immune-Mediated Necrotizing Myopathy.

INTRODUCTION/AIMS: Immune-mediated necrotizing myopathy (IMNM) is a severe autoimmune myopathy causing proximal muscle weakness. Its underlying immunopathogenesis remains incompletely understood, limiting the development of targeted therapies. To elucidate disease mechanisms and inform therapeutic strategies, this study characterized the peripheral immune profile of treatment-naïve IMNM patients.

METHODS

This retrospective study analyzed serum cytokine levels, complement proteins (C3, C4), immunoglobulins (IgA, IgG, and IgM), and peripheral blood lymphocyte subsets in 28 treatment-naïve IMNM patients during the active disease phase and 25 healthy controls at Tongji Hospital from August 2023 to March 2025.

RESULTS

Compared with healthy controls, IMNM patients showed significantly elevated serum concentrations of interleukin-6 and interferon-γ (both p < 0.001). IgG and IgM levels were also markedly higher in the IMNM group (p = 0.003; p = 0.002). The number and percentage of B cells were significantly increased in IMNM patients (both p = 0.004). The number and percentage of CD8+ T cells were similarly elevated (p = 0.009; p = 0.004). In contrast, the proportion of CD4+ T cells was significantly reduced (p = 0.002), and the absolute count of natural killer cells was also significantly reduced (p = 0.004).

DISCUSSION: IMNM exhibits a distinct peripheral immune landscape, characterized by enhanced humoral immunity potentially driven by CD8+ T cell-mediated mechanisms, accompanied by reduced circulating natural killer cells. These findings suggest potential biomarkers for disease activity and may inform targeted immunotherapies. Further studies are needed to validate these immune alterations and clarify their role in IMNM pathogenesis.