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Lai et al. Imbalance of NK and B cell subsets in GMG exacerbation

Key words: blood samples obtained from 54 MG patients and 10 healthy controls were surveyed using
Myasthenia gravis, flow cytometry. MG patients were subdivided into the ocular MG, generalized MG (GMG) in
lymphocyte subsets, exacerbation stage and GMG in remission stage. Results: The percentage of Breg cells was
natural killer cells, significantly decreased in both the exacerbation stage (6.93 ± 1.18) and remission stage (6.56
B regulatory cells ± 1.32) of GMG patients compared to healthy controls (15.97 ± 2.88). The percentage of NK
cells were significantly increased in GMG patients in remission stage (20.69 ± 3.45) compared
to healthy controls (11.33 ± 0.95). Frequency of NK cells in the patients in remission stage
was significantly increased compared to patients in exacerbation (20.69 ± 3.45 vs. 12.32 ±
1.42). Conclusion: The Breg cells are involved in the pathogenesis of GMG, and NK cells are
closely associated with the fluctuation of MG symptoms. NK cells could be a useful marker for
MG activity and for monitoring effectiveness of immunotherapy.

INTRODUCTION generally considered to be pathogenic in the majority
of autoimmune diseases. Recent evidence indicates
Myasthenia gravis (MG) is one of the most common that specific B cell subsets can negatively regulate
autoimmune neurological diseases and affects the immune responses by constraining Th1 and Th17
neuromuscular junction. Although there are many responses, indicative of the existence of regulatory B
[1]
therapeutic methods such as immunosuppressive (Breg) cells. Natural killer (NK) cells predominantly
[22]
therapy and steroids which are generally regarded as participate in the innate immune response to
the effective preventive measures leading to marked infections. NK cell-derived interferon-gamma activates
symptomatic improvement in the majority of MG Th1 helper cells, and NK cells can impact acquired
[23]
patients, there are many cases who still experience immunity. The subsets of lymphocytes mentioned
fluctuating muscle weakness and fatigability to some above have been demonstrated to be involved in
degree, or develop myasthenic crisis even after a the pathogenesis of MG, but the role of lymphocyte
clinical remission. [2-5] Yet the factors predicting the subsets in symptomatic exacerbation in MG patients
symptomatic fluctuation have not been well defined. is not fully understood.

MG is mainly mediated by acetylcholine receptor NK cells which play an important role during viral
antibodies (AChR-Ab), which were demonstrated infection and tumor diseases, were considered to be
to be associated with the severity of disease in involved in the regulation of autoimmunity in animal
individuals. However, the heterogeneity of AChR-Ab models and in humans. [24-26] NK cell numbers were
[6]
and no elevated titers of AChR-ab in the minority of MG found to decline with progression of most autoimmune
patients limited the clinical significance of measuring diseases of humans. [27-29] Interestingly, the number
the antibodies. [1,7] In addition, there are some patients of NK cells was increased significantly after
with elevated titers of antibodies against muscle- plasmapheresis in patients with MG, indicating that
specific kinase (MuSK), Titin, RyR and LRP4, [8-11] they may become an important marker for monitoring
signifying the heterogeneity of the autoimmune clinical activation in MG patients. [16]
disease. Identification of specific markers of disease
activity and severity is of great interest to clinicians. Traditionally, B cells have been thought to contribute
Changes in peripheral lymphocyte subsets were to the antigen (Ag)-specific autoantibody production.
reported in patients with MG as well as patients with Nonetheless, the role of B cells extends beyond the
other autoimmune diseases, including systemic lupus production of antibodies in autoimmune diseases.
erythematosus, rheumatoid arthritis and Sjogren’s Recently, B cell subsets with regulatory functions
[12]
[13]
syndrome, [14,15] suggesting that these abnormal were identified and the studies focused on Breg cells,
distributions of lymphocyte subsets may be involved in also known as B10 cells, which express IL-10 and
the pathogenesis of autoimmune diseases. [16-19] CD4 CD1d CD5 CD19 phenotypes. [30-32] Recent studies
+
+
+
+
T helper cells have an important role in an experimental showed that Breg cells can prevent the development
animal model of myasthenia gravis (EAMG) and of EAMG, and were involved in patients with
[33]
MG patients as they influence autoreactive B cell autoimmune diseases. [31,34-36] However, whether there
production of anti-AChR antibodies. Th1, Th2, Th17 are corresponding changes in Breg cells associated
[20]
and regulatory T (Treg) cells, which were differentiated with severity of diseases remains elusive.
from Naïve CD4 T cells, have been shown to be
+
involved in the pathogenesis of MG. B cells, In this study, we investigated the changes in peripheral
[21]
because of the key contribution to humoral immune NK cells and Bregs in MG patients experiencing
responses involving the secretion of antibodies, are deterioration, in attempt to find a reliable marker
180 Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ September 18, 2017