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. 2025 Nov;12(6):e200468.
doi: 10.1212/NXI.0000000000200468. Epub 2025 Sep 18.

Correlation of C-Reactive Protein With Severe Fatigue in Patients With Myasthenia Gravis

Annabel M Ruiter  1 , Krista E van Meijgaarden  2 , Simone A Joosten  2 , Pietro Spitali  3 , Maartje G Huijbers  1   3 , Erik W van Zwet  4 , Umesh A Badrising  1 , Martijn Tannemaat  1 , Jan J Verschuuren  1
Affiliations

Correlation of C-Reactive Protein With Severe Fatigue in Patients With Myasthenia Gravis

Annabel M Ruiter et al. Neurol Neuroimmunol Neuroinflamm. 2025 Nov.

Abstract

Background and objectives: Most patients with myasthenia gravis (MG) suffer from fatigue, which can be defined as a subjective lack of energy and difficulty in initiating or sustaining voluntary activities. This is conceptually different from muscle weakness or muscle fatigability. Fatigue is one of the most reported symptoms in MG and has been hypothesized to be an innate mechanism to minimize muscle activity in order to protect muscles from (further) damage. The exact pathophysiology of fatigue remains unclear, and it is very likely a multifactorial phenomenon. The aim of this study was to provide a better understanding on the pathophysiology of fatigue in MG.

Methods: We analyzed 38 serum biomarkers including various cytokines and myokines in a cohort of 116 anti-acetylcholine receptor-positive patients with MG. A multivariate linear regression analysis for each biomarker was performed in search for a correlation with fatigue. The following preselected covariates were included in the primary analysis: sex, age, disease severity, depression and anxiety scores, nonsteroid immune suppressive medication, and cumulative prednisone dosage in the past 6 months.

Results: Severe fatigue was present in 64% of patients. Results show a robust correlation between fatigue and C-reactive protein (CRP) in the primary analysis. This correlation persisted when additionally adjusting for BMI, strenuous physical activities, and hemoglobulin levels.

Discussion: Our findings suggest that chronic low-grade inflammation, mediated by CRP, contributes to the pathogenesis of fatigue in MG. This aligns with the hypothesis that local peripheral inflammatory processes induce systemic inflammatory cascades responsible for fatigue.

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Conflict of interest statement

A.M. Ruiter, K.E. van Meijgaarden, S.A. Joosten, and P. Spitali report no disclosures. M.G. Huijbers is a consultant for Argenx and receives financial support from the LUMC Gisela Thier fellowship 2021. E.W. van Zwet reports no disclosures. U.A. Badrising reports that the LUMC receives funding and compensation for clinical trial activities on behalf of U.A. Badrising from the Prinses Beatrix Fund, Association Française contre les Myopathies and Fulcrum Therapeutics. M.R. Tannemaat reports consultancies for Argenx, UCB Pharma, Johnson and Johnson, Peervoice, and Medtalks, and research funding from ZonMW, NWO, ArgenX, and NMD Pharma. All reimbursements were received by the LUMC. M.R. Tannemaat had no personal financial benefit from these activities. J.J.G.M. Verschuuren is a consultant for Argenx, receives financial support from Target2B! consortium and Prinses Beatrix Spierfonds, and has been involved in trials or consultancies for Argenx, Alexion, and Rapharma. The LUMC received royalties from IBL and Argenx for MG research. All reimbursements were received by the LUMC. Go to Neurology.org/NN for full disclosures.

Figures

Figure 1
Figure 1. Study Flowchart
Figure 2
Figure 2. Median Fatigue Scores (CIS-f) per MGFA Class
Horizontal line indicates cutoff for clinically relevant fatigue (≥35), boxes at bottom of figure shows percentage clinically relevant fatigue per MGFA class. CIS-f = Checklist Individual Strength–Fatigue; MGFA = Myasthenia Gravis Foundation of America; *p < 0.01; **p < 0.001.
Figure 3
Figure 3. Switch From No Severe or Severe Fatigue From Baseline to the Second Visit
Figure 4
Figure 4. Change Over Time (Delta) of Disease Severity (MG-ADL), Fatigue (CIS-f), and C-Reactive Protein (CRP)
See this image and copyright information in PMC

References

    1. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren J. Myasthenia gravis. Nat Rev Dis Primers. 2019;5(1):30. doi: 10.1038/s41572-019-0079-y - DOI - PubMed
    1. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14(10):1023-1036. doi: 10.1016/S1474-4422(15)00145-3 - DOI - PubMed
    1. Ruiter AM, Verschuuren J, Tannemaat MR. Prevalence and associated factors of fatigue in autoimmune myasthenia gravis. Neuromuscul Disord. 2021;31(7):612-621. doi: 10.1016/j.nmd.2021.04.002 - DOI - PubMed
    1. Ruiter AM, Verschuuren J, Tannemaat MR. Fatigue in patients with myasthenia gravis. A systematic review of the literature. Neuromuscul Disord. 2020;30(8):631-639. doi: 10.1016/j.nmd.2020.06.010 - DOI - PubMed
    1. Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet. 2004;363(9413):978-988. doi: 10.1016/S0140-6736(04)15794-2 - DOI - PubMed