| Background/Objective:IL-21/21R is a newly identified cytokine and its receptor that play important role in pathogenesis of autoimmune disease. Recently, studies have reported increased serum IL-21 and its receptor in various autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA) and, systemic lupus erythematosus (SLE). This study aimed to see the changes in IL-21/21R in peripheral blood AchR specific B cells of myasthenia gravis (MG) patients with glucocorticoid treatment and further clarify its role in pathogenesis of MG.Methods:20 MG patients and 15 healthy controls were enrolled in this prospective study. Measurement of serum IL-21 concentration in healthy controls and MG patients before and after glucocorticoid treatment was done using ELISA whereas expression of IL-21 RmRNA in PBMCs and AchR specific B cells were determined by RT-PCR and flow cytometry respectively. Additionally, serum levels of specific anti-AChR-IgG and its subclasses IgG1, IgG2, IgG3 were also determined by ELISA.Results:(1) Serum IL-21 concentration in MG patients was higher before treatment 86.94±14.47 (pg/ml) and decreased significantly after glucocorticoid treatment 35.84±16.13 (pg/ml) (p<0.05). Serum IL-21 concentration in control group was 16.65±6.65 (pg/ml), relatively lower as compared with MG patients.(2) Relative OD values of IL-21 R mRNA expressed in PBMCs of MG patients was higher 0.137±0.023 and significantly decreased after glucocorticoid treatment 0.114±0.023 (P<0.05), while it was 0.107±0.025 in control group.(3) Serum levels of the specific anti-AchR-IgG and its subclasses anti-AchR-IgG1, anti-AchR-IgG2 and, anti-AchR-IgG3 antibody levels did not show any significant change with glucocorticoid treatment.(4) Expression of specific AchR+CD19+B cells in peripheral blood of MG patients (1.78±0.27) showed significant decrease with glucocorticoid treatment (0.81±0.17) (p<0.05). Similarly, expression of IgG+CD19+B cells (1.78±0.53) before treatment showed significant decrease after treatment (0.81±0.23) (p<0.05) along with significant decrease in expression of specific AchR+IgG+CD19+B cells, (0.77±0.29) and (0.35±0.12) (p<0.05) before and after treatment respectively. Also, expression of IL-21R+CD19+B cells was 1.79±0.64, which decreased significantly with treatment 1.01±0.33 (p<0.05). Importantly, expression of specific AchR+IL-21R+CD19+B cells (0.68±0.15) before treatment showed significant decrease with glucocorticoid treatment (0.39±0.12) (p<0.05).(5) In MG patients, serum concentration of IL-21 showed positive correlation with specific serum anti-AchR-IgGi levels at both occasions, before (r=0.732) and after glucocorticoid treatment (r=0.516) (p<0.05).(6) Serum IL-21 concentration also showed positive correlation with expression of specific AchR+IgG+CD19+B cells before(r=0.454, p<0.05) and after glucocorticoid treatment (r=0.538, p<0.05).(7) Lastly, difference in serum IL-21 concentration (before treatment-after glucocorticoid treatment), dIL-21 showed positive correlation with the difference in QMG score (before treatment-after glucocorticoid treatment), dQMG (r=0.533, p<0.05) among MG patients.Conclusion:1. Glucocorticoid treatment might decreases expression of B cells, especially AChR specific IL-21R+B cells and in turn may affect the secretion of anti-AchR-IgG1 antibody in MG.2. This decrease in expression of AchR specific B cells is possibly the result of reduced serum IL-21 levels affecting B cell proliferation and maturation further consolidating role of IL-21/21R in MG pathogenesis.
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