Myasthenia gravis and immunological markers
11st Department of Neurology, Aristotelian University, Thessaloniki, Greece
2Microbiological Laboratory, AHEPA Hospital

The nuromuscular junction is the target of a number of disorders that impair transmission from nerve to muscle. These diseases may compromise the postsynaptic junction and the acetylcholine receptor (AchR). With a deficiency of the AchR there is an impairment of the translation of information from neurotransmitter release to development of the muscle action potential and muscle contraction. Myasthenia gravis (MG) is the most prominent disease generally responsive to immunosupressive medication.

Myasthenia gravis is characterized by weakness and fatigability of skeletal muscles. The incidence of MG is less than 1 per 100.000 and is more common among females in the first several decades. The clinical syndrome is characterized by various weakness and fatigability, which may occur as the day progresses or with exertion and improvement may develop with rest. The extraocular and eyelid muscles can be affected early and usually asymetrically. While in a small percentage of cases the disease remains confined to the eyes, more typically it gradually becomes more generalized, involving the limps, especially the proximal musculature. Swallowing difficulty can lead to choking and to aspiration of food and secretions. The major concern is weakness of the respiratory muscles leading to impairment of breathing and respiratory myasthenic crises.

In the present study we examined twenty-six patients, thirteen male and thirteen female, suffered from MG, during clinical exacerbation, without taking any immunosuppresive therapy and twenty-six healthy individuals. We detected the following mentioned immunological markers: subpopulations of T-cels, using flow cytometry in blood of MG patients, IL-6, IL-6 R, anti-MAG, anti GM1, anti-GD1b and TNFa using ELISA in the serum of the patients. Our results indicate:

  1. Elevated value of the ratio CD4/CD8 to all patients, mainly causing to the increasing of CD4+ rather to the decreasing of CD8+ subtype.
  2. All patients showed mild elevated titer of MAG antibodies.
  3. All patients showed elevated titer of GD1b antibodies.
  4. Thirteen patients (50%) showed mild increasing of IL-6.
  5. All patients showed increasing of IL-6 R.
  6. TNFa and antibodies against GM1 were normal.
  7. All the healthy individuals showed normal values of the above mentioned immunological markers.

A generalized immune dysregulation occurs in MG patients, mostly during the acute phase of the disease, involving activation of autoreactive T-cells. In normal individuals these activated T-cells are deleted by activation-induced apoptosis, but in individuals predisposed to MG they survive, proliferate and damage the neuromuscular junction. When activated T-cells enter the target organ they are reactivated by antigen-presenting cells and deleted by activation-induced apoptosis, before producing significant target organ damage. This is in contrast to the situation in peripheral lymphoid organs, where reactivation of T-cells by professional antigen-presenting cells results in sufficient costimulation-induced up-regilation to allow T-cells proliferation and survival as memory T-cells. T-cell activity in the blood indirectly reflects the ongoing inflammatory responce at the primary site, accounting for the lack of correlation between changes in the blood and the clinical status of the patients. Helper-inducer (CD4+) and suppressor-inducer (CD8+) T-cells have been recently renamed as memory and naive T-cells respectively.

Our results indicate that MG patients show increased levels of CD4+ T-cells during the acute phase of the disease.

IL-6 is produced by peripheral blood mononuclear cells and associated with immune activation. We detected small levels of IL-6 but elevated amounts of IL-6 R.

The increased values of antibodies against the gagliosides indicate the disturbance of endocytosis of the receptors and are associated with the presence of myasthenic crisis.

Our study suggest that MG is an autoantibody-mediated and T-cell dependent autoimmune disease with an unclear immunological background which must be investigated.

Key words: Myasthenia gravis, immunological markers.