The objective of this study was to compare informative value of traditional approach (anti-AChR antibody radioimmunoassay) and evaluation of metabolic shifts by laser correlation spectroscopy in myasthenia gravis. The method based on changes in spectral characteristics of laser radiation caused by scattering in a disperse system yields a histogram reflecting particle contribution into light scatter as a function of particle radius in nanometers. The spectrum of anti-AChR-positive serum is characterized by appreciably increased contribution of particles with a radius 4.6–6.2？nm. Binding of serum components with solubilized AChR confirms that this peak is determined by elevated concentration of antibodies to this receptor. The search for the relationship between the disease severity and the distribution pattern of subfraction serum components revealed three informative zones: 6–15, 27–67, and 127–223？nm. In patients without disturbances of vital functions, the contribution of the first zone particles into light scatter increases and that of the third zone particles decreases. Considerable differences attaining the level of statistical significance in zones 4–6 and 20？nm were revealed in the spectra of serum from patients with myasthenia gravis of the same severity with and without thymoma. This opens prospects for dynamic monitoring of the efficiency of therapy. 1. Introduction According to current concept of myasthenia gravis (MG) pathogenesis, autoimmune aggression towards certain molecular structures of the skeletal muscle and neuromuscular junction is the leading pathophysiological factor responsible for the development of clinical manifestations of this disease [1–3]. Numerous studies have demonstrated that postsynaptic nicotinic acetylcholine receptors (AChR) are more often attacked in MG: 80–85% myasthenia patients have elevated concentrations of antibodies to these receptors [4]. Pathophysiological role of antibodies to AChR has been confirmed in animal experiments reproducing the development of myasthenic process after immunization with AChR preparations or injection of the serum from myasthenic patients [5, 6]. Antibody-mediated autoimmune processes impair neuromuscular transmission due to loss of functionally active AChR, which impairs acetylcholine binding to the receptor and reduces the probability of the transmitter-receptor interaction. Moreover, antibody fixation to the postsynaptic membrane leads to destruction of junction folds and structural modification of the synapse. Hence, not only the density of AChR decreases, but also the
References
[1]
A. Vincent, “Autoimmune disorders of the neuromuscular junction,” Neurology India, vol. 56, no. 3, pp. 305–313, 2008.
[2]
A. Vincent, D. Beeson, and B. Lang, “Molecular targets for autoimmune and genetic disorders of neuromuscular transmission,” European Journal of Biochemistry, vol. 267, no. 23, pp. 6717–6728, 2000.
[3]
F. Romi, N. E. Gilhus, and J. A. Aarli, “Myasthenia gravis: clinical, immunological, and therapeutic advances,” Acta Neurologica Scandinavica, vol. 111, no. 2, pp. 134–141, 2005.
[4]
J. M. Lindstrom, “Acetylcholine receptors and myasthenia,” Muscle & Nerve, vol. 23, no. 4, pp. 453–477, 2000.
[5]
F. Baggi, C. Antozzi, C. Toscani, and C. Cordiglieri, “Acetylcholine receptor-induced experimental myasthenia gravis: what have we learned from animal models after three decades?” Archivum Immunologiae et Therapiae Experimentalis, vol. 60, no. 1, pp. 19–30, 2012.
[6]
R. Tarrab-Hazdai, A. Aharonov, O. Abramsky, I. Silman, and S. Fuchs, “Proceedings: animal model for myasthenia gravis: acetylcholine receptor-induced myasthenia in rabbits, guinea pigs and monkeys,” Israel Journal of Medical Sciences, vol. 11, no. 12, p. 1390, 1975.
[7]
A. G. Engel, M. Tsujihata, J. M. Lindstrom, and V. A. Lennon, “The motor end plate in myasthenia gravis and in experimental autoimmune myasthenia gravis. A quantitative ultrastructural study,” Annals of the New York Academy of Sciences, vol. 274, pp. 60–79, 1976.
[8]
C. Krarup, “Evoked responses in normal and diseased muscle with particular reference to twitch potentiation,” Acta Neurologica Scandinavica, vol. 68, no. 5, pp. 269–315, 1983.
[9]
A. Evoli, A. P. Batocchi, and P. Tonali, “A practical guide to the recognition and management of myasthenia gravis,” Drugs, vol. 52, no. 5, pp. 662–670, 1996.
[10]
D. V. Sidnev, M. Y. Karganov, N. I. Shcherbakova, I. B. Alchinova, and A. G. Sanadze, “Antibodies to acetylcholine receptors in patients with different clinical forms of myasthenia and Lambert-Eaton myasthenic syndrome,” Neuroscience and Behavioral Physiology, vol. 37, no. 2, pp. 129–131, 2007.
[11]
M. Karganov, I. Alchinova, E. Arkhipova, and A. V. Skalny, “Laser correlation spectroscopy: nutritional, ecological and toxic aspects,” in Biophysics, A. N. Misra, Ed., pp. 1–16, InTech, Rijeka, Croatia, 2012.
[12]
L. A. Piruzyan, I. E. Kovalev, V. L. Kovaleva et al., “Laser correlation spectroscopy of macromolecular complexes in blood serum as an effective method of monitoring the progress of bronchial asthma in children,” Doklady Biochemistry and Biophysics, vol. 395, no. 1-6, pp. 114–117, 2004.
[13]
I. E. Kovalev, M. Y. Karganov, E. I. Rumyantseva, and O. I. Kovaleva, “Laser correlation spectroscopy as an effective method of detection of DNA-containing and other macromolecular complexes in blood serum of patients with diabetes mellitus,” Doklady Biochemistry and Biophysics, vol. 386, pp. 281–283, 2002.
[14]
E. I. Rumyantseva, I. E. Kovalev, O. I. Kovaleva, and M. Y. Karganov, “Laser correlation spectroscopy of macromolecular complexes in blood serum is an efficient method for detecting insulin overdose and correction of the insulin therapy for diabetes mellitus in children,” Doklady Biochemistry and Biophysics, vol. 402, no. 1–6, pp. 210–213, 2005.
[15]
M. Karganov, O. Kovaleva, A. Sanadze, D. Sidnev, V. Pivovarov, and S. Landa, “Comparative analysis of the informative value of radioimmunoassay and laser correlation spectroscopy in myasthenia gravis and myasthenic syndromes,” Journal of Neurology, vol. 8, supplement 1, pp. 26–29, 2003 (Russian).
[16]
R. J. Barohn, D. McIntire, L. Herbelin, G. I. Wolfe, S. Nations, and W. W. Bryan, “Reliability testing of the quantitative myasthenia gravis score,” Annals of the New York Academy of Sciences, vol. 841, pp. 769–772, 1998.
[17]
M. Y. Karganov, A. V. Skalny, I. B. Alchinova et al., “Combined use of laser correlation spectroscopy and ICP-AES, ICP-MS determination of macro- and trace elements in human biosubstrates for intoxication risk assessment,” Trace Elements and Electrolytes, vol. 28, no. 2, pp. 124–127, 2011.
[18]
A. Vincent, P. J. Whiting, M. Schluep et al., “Antibody heterogeneity and specificity in myasthenia gravis,” Annals of the New York Academy of Sciences, vol. 505, pp. 106–120, 1987.
[19]
A. G. Engel, “The investigation of congenital myasthenic syndromes,” Annals of the New York Academy of Sciences, vol. 681, pp. 425–435, 1993.
[20]
B. Lang and J. Newsom-Davis, “Immunopathology of the Lambert-Eaton myasthenic syndrome,” Springer Seminars in Immunopathology, vol. 17, no. 1, pp. 3–15, 1995.
[21]
D. B. Drachman, “Medical progress: myasthenia gravis,” The New England Journal of Medicine, vol. 330, no. 25, pp. 1797–1810, 1994.
