Short-term effect of low-dose rituximab on myasthenia gravis with muscle-specific tyrosine kinase antibody

Muscle Nerve. 2021 Jun;63(6):824-830. doi: 10.1002/mus.27233. Epub 2021 Apr 6.

Abstract

Introduction/aims: The study aims to investigate the short-term efficacy of low-dose rituximab and its effect on immunological biomarker levels in myasthenia gravis (MG) patients with antibodies against muscle-specific tyrosine kinase (MuSK-MG).

Methods: Twelve MuSK-MG patients were enrolled in this prospective, open-label, self-controlled pilot study. Clinical severity was evaluated at baseline and 6 mo after a single rituximab treatment (600 mg). B lymphocyte subtypes, MuSK antibody titers, together with levels of immunoglobulins, serum B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L, and four exosomal microRNAs were evaluated. A correlation matrix to reveal pairwise relationships among above variables was also generated.

Results: The single rituximab treatment significantly lowered the clinical severity scores and reduced daily dosage of prednisone (P = .032) at 6 mo. MuSK antibody titers decreased (P = .035) without significant changes in immunoglobulin levels. Serum BAFF level increased (P = .010), which negatively correlated with the percentages of B cells in lymphocytes as well as clinical severity. Additionally, serum exosomal miR-151a-3p showed a reduction of 28.1% (P = .031).

Discussion: We confirmed the clinical efficacy of low-dose rituximab in MuSK-MG, accompanied by a decrease in MuSK antibody titers and an increase in serum BAFF. Serum BAFF levels negatively correlated with B-cell counts as well as clinical severity.

Keywords: B-cell activating factor (BAFF); low dose; muscle specific tyrosine kinase (MuSK); myasthenia gravis; rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies
  • Female
  • Humans
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Myasthenia Gravis / drug therapy*
  • Myasthenia Gravis / immunology
  • Receptor Protein-Tyrosine Kinases / immunology*
  • Receptors, Cholinergic / immunology*
  • Rituximab / administration & dosage
  • Rituximab / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Autoantibodies
  • Immunologic Factors
  • Receptors, Cholinergic
  • Rituximab
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases