Influence of oxidant stress on clinical manifestations and quality of life in patients with generalized myasthenia gravis

January 22, 2020
643
Specialities :
Resume

The aim was to study the effect of oxidative stress indicators on the clinical manifestations of myasthenia gravis, as well as on the qua­lity of life of patients. Materials and methods. The study included 147 patients with generalized myasthenia gravis (mean age 53.0 (37.0–65.0) years, 98 (66.7%) women and 49 (33.3%) men). 10 almost healthy individuals formed a control group to compare oxidative stress indicators. To quantify the clinical manifestations of myasthenia gravis, patients were assessed using the Qualitative Myasthenia Gravis Scale, and fatigue was assessed using the Fatigue Severity Scale. Quality of life was assessed using the Myasthenia Gravis Quality of Life-15 scale. The level of total protein, sulfhydryl groups, glutathione-­dependent enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase), reduced and oxidized glutathione, heat shock protein with a mass of 70 kDa (HSP70) and nitrotyrosine as the main indicator of nitrosine stress were determined. For mathematical data processing, methods of parametric and nonparametric statistics were used. Results. The severe course of myasthenia gravis (according to the Qualitative Myasthenia Gravis Scale) had direct connections with nitrotyrosine and oxidized glutathione, while with other enzymes of the antioxidant system, mostly direct and strong correlations were determined (the higher the protein content, the higher the level of oxidative stress, the worse the condition of the patient with myasthenia). For the Qualitative Myasthenia Gravis Scale, the strongest association was determined with glutathione peroxidase (ρ=–0.78; p<0.001), for the Myasthenia Gravis — Activity of Daily Living Scale and the Fatigue Severity Scale — with glutathione reductase (ρ=–0.69 and ρ=–0.54 respectively; p<0.001), for the Myasthenia Gravis Quality of Life-15 scale — with sulfhydryl groups and glutathione reductase (both ρ=–0.62; p<0.001). Sulfhydryl groups had a strong direct correlation with reduced glutathione (r=0.83; p<0.001), and the reverse one with oxidized glutathione (r=–0.80; p<0.001). Strong feedback was determined between nitrotyrosine and reduced glutathione (r=–0.71; p<0.001), reduced and oxidized glutadione (r=–0.82; p<0.001). HSP70 correlates with both glutathione-dependent enzymes — glutathione peroxidase (r=0.63; p<0.001), glutathione reductase (r=0.68; p<0.001), glutathione-S-transferase (r=0.50; p<0.001), and with an indicator of nitrosine stress — nitrotyrosine (r=–0.64; p<0.001). In general, the coefficient of canonical correlation between the indicators of the clinical and neurological state of patients with myasthenia gravis and the complex of biochemical parameters associated with oxidative stress is R=0.85 (χ2=81.60; p<0.001). Conclusions. Indicators of oxidative stress affect the development of generalized myasthenia gravis and its severity, and also have an impact on the daily activity of patients, their level of fatigue, and quality of life indicators.

Published: 22.01.2020

 

References:

  • Kalbus O.I. (2019a) Immunological markers of myasthenia development. UMJ, 2(2): 24–26 (https://doi.org/10.32471/umj.1680-3051.130.140164).
  • Kalbus O.I. (2019b) Medical-statistical and epidemiological characteristics of the prevalence of myasthenia gravity in Ukraine. UMJ, 4(2): 42–45 (https://doi.org/10.32471/umj.1680-3051.132.161828).
  • Adamczyk-Sowa M., Bieszczad-Bedrejczuk E., Galiniak S. et al. (2017) Oxidative modifications of blood serum proteins in myasthenia gravis. J. Neuroimmunol., 305: 145–153 (https://doi.org/10.1016/j.jneuroim.2017.01.019).
  • Andersen J.B., Heldal A.T., Engeland A., Gilhus N.E. (2014) Myasthenia gravis epidemiology in a national cohort; combining multiple disease registries. Acta Neurologica Scandinavica. Supplementum, 198: 26–31 (https://doi.org/10.1111/ane.12233).
  • Barohn R., Mcintire D., Herbelin L. et al. (1998) Reliability Testing of the Quantitative Myasthenia Gravis Scorea. Annals of the New York Academy of Sciences, 841(1): 769–772.
  • Blum S., Lee D., Gillis D. et al. (2015) Clinical features and impact of myasthenia gravis disease in Australian patients. J. Clin. Neurosci., 22(7): 1164–1169 (https://doi.org/10.1016/j.jocn.2015.01.022).
  • Brambilla D., Mancuso C., Scuderi M. et al. (2008) The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile. Nutrition J., 7(1) (https://doi.org/10.1186/1475-2891-7-29).
  • Breiner A., Widdifield J., Katzberg H. D. et al. (2016) Epidemiology of myasthenia gravis in Ontario, Canada. Neuromusc. Dis., 26(1): 41–46 (https://doi.org/10.1016/j.nmd.2015.10.009).
  • Breiner A., Young J., Green D. et al. (2015) Canadian administrative health data can identify patients with myasthenia gravis. Neuroepidemiology, 44: 108–113 (https://doi.org/10.1159/000375463).
  • Carr A.S., Cardwell C.R., McCarron P.O., McConville J. (2010) A systematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurology, 10: 46 (https://doi.org/10.1186/1471-2377-10-46).
  • Engel A.G. (Ed.) (2012) Myasthenia gravis and myasthenic disorders. Oxford University Press, Oxford, 304 p.
  • Jaretzki A., Barohn R.J., Ernstoff R.M. et al. (2000) Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology, 55: 16–23.
  • Krishnaswamy A., Cooper E. (2011) Reactive oxygen species inactivate neuronal nicotinic acetylcholine receptors through a highly conserved cysteine near the intracellular mouth of the channel: implications for diseases that involve oxidative stress. J. Physiol., 590(1): 39–47 (https://doi.org/10.1113/jphysiol.2011.214007).
  • Kulaksizoglu I. (2007) Mood and anxiety disorders in patients with myasthenia gravis: aetiology, diagnosis and treatment. CNS Drugs, 21: 473–481 (https://doi.org/10.2165/00023210-200721060-00004).
  • Nagappa M., Mahadevan A., Gangadhar Y. et al. (2019) Autoantibodies in acquired myasthenia gravis: clinical phenotype and immunological correlation. Acta Neurol. Scandinav., 139(5): 428–437.
  • Venkatesham A., Babu P.S., Sagar J.V., Krishna D.R. (2005) Effect of reactive oxygen species on cholinergic receptor function. Indian J. Pharmacol., 37: 366–370.
  • Vinge L., Jakobsen J., Andersen H. (2018) Muscle weakness and functional disability in patients with myasthenia gravis. Muscle Nerve, 59(2): 218–223 (https://doi.org/10.1002/mus.26356).
  • Wolfe G., Herbelin L., Nations S. et al. (1999) Myasthenia gravis activities of daily living profile. Neurology, 52(7): 1487–1487.
  • Yang D., Su Z., Wu S. et al. (2016) Low antioxidant status of serum bilirubin, uric acid, albumin and creatinine in patients with myasthenia gravis. Int. J. Neurosci., 126(12): 1120–1126 (https://doi.org/10.3109/00207454.2015.1134526).