Abstract
Myasthenia gravis (MG) is an autoimmune disease. A proportion of MG patients did not get satisfactory results after treatment with pyridostigmine and prednisone. Jia Wei Bu Zhong Yi Qi (Jia Wei BZYQ) decoction, a water extract from multiple herbs, has been demonstrated to be effective in the treatment of multiple “Qi deficiency type” diseases including MG in China. In this text, we investigated protein alterations in the plasma from healthy volunteers (C), MG patients without any treatment (T1), MG patients with routine western medical treatment (T2), and MG patients with combined treatments of Jia Wei BZYQ decoction and routine western medicines (T3) and identified some potential proteins involved in the pathogenesis and treatment of MG. iTRAQ (isobaric tags for relative and absolute quantitation) and 2D-LC-MS/MS (two-dimensional liquid chromatography-tandem mass spectrometry technologies) were employed to screen differentially expressed proteins. The identification, quantification, functional annotation, and interaction of proteins were analyzed by matching software and databases. In our project, 618 proteins were identified, among which 447 proteins had quantitative data. The number of differentially expressed proteins was 110, 117, 143, 115, 86, and 158 in T1 vs. C, T2 vs. C, T2 vs. T1, T3 vs. C, T3 vs. T1, and T3 vs. T2 groups, respectively. Functional annotation results showed that many differentially expressed proteins were closely associated with immune responses. For instance, some key proteins such as C-reactive protein, apolipoprotein C-III, apolipoprotein A-II, alpha-actinin-1, and thrombospondin-1 have been found to be abnormally expressed in T3 group compared to T1 group or T2 group. Interaction network analyses also provided some potential biomarkers or targets for MG management.
Highlights
Myasthenia gravis (MG) is a disorder of neuromuscular transmission with an incidence of 0.3 to 2.8 cases per 100,000 people and an annual mortality of 0.06 to 0.89 per million people worldwide [1,2,3]
musclespecific tyrosine kinase (MuSK) antibodies are found in 1–10% of MG patients, and lipoprotein receptorrelated protein-4 (LRP4) antibodies can be detected in approximately 7% of MG patients without antibodies against acetylcholine receptor (AChR) and MuSK [8]
It is presumed that thymus is not related to the pathogenesis of MG in MG patients with MuSK antibodies, and extremely rare MuSK antibodies are found in MG patients with thymoma [4]
Summary
Myasthenia gravis (MG) is a disorder of neuromuscular transmission with an incidence of 0.3 to 2.8 cases per 100,000 people and an annual mortality of 0.06 to 0.89 per million people worldwide [1,2,3]. MG patients can generate autoantibodies against postsynaptic neuromuscular proteins and epitopes such as acetylcholine receptor (AChR), musclespecific tyrosine kinase (MuSK), and lipoprotein receptorrelated protein-4 (LRP4) to attack the body’s tissues [4,5,6]. MG patients with AChR or MuSK antibodies usually develop more severe symptoms (51-52% MGFA I-II at onset) compared with LRP4 antibody-positive subgroup [7,8,9]. MG patients with double-positive autoantibodies of AChR/LRP4 or MuSK/LRP4 have more severe symptoms relative to any single-positive MG subgroup [9]. MG patients with positive LRP4 antibodies usually have ocular or mild generalized symptoms (85% with MGFA grade I or II at disease onset), and some have thymic changes (31% hyperplasia, 29% involuted thymus, 7% atrophy, 33% normal thymus, and none with thymoma) [9]. MG patients with positive LRP4 antibodies usually have ocular or mild generalized symptoms (85% with MGFA grade I or II at disease onset), and some have thymic changes (31% hyperplasia, 29% involuted thymus, 7% atrophy, 33% normal thymus, and none with thymoma) [9]. e average age for MG patients is 33.4 years for females and 41.9 years for males at disease onset [9]
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