| Objective:The clinical data of MG patients treated by Lymphoplasmapheresis (LPE) or glucocorticoid pulse (GP) in the Xiangya hospital of CSU in the last ten years were retrospectively analysised, in order to evaluate the effectiveness of LPE on the MG treatment. By prospective study, the improvement of the clinical score, the changes of the immunoglobulin、complement、peripheral blood mononuclear cells (PBMCs) and monocytes, the levels of sIL-21and anti-AChR-Ab, the percentage of AChR+IL-21R+B cells and AChR+IgG+B cells in MG patients before and after receving LPE therapy were detected and compared. The influence of LPE on immune cells, especially AChR specific B cells in MG patients were discussed, further the relationship between these results were analyzed. So as to reveal the immune mechanism of LPE on the treatment of MG and offer a theoretical guide for the theroputic strategy MG.Methods:Study1. The improvement of the clinical score、hospital stays and tracheostomy rate in LPE and GP patients were compared by analysing the clinical data from MG patients treated by the two theraputic method in Xiangya hospital of CSU in2002-2012, in order to evaluate the effectiveness of LPE. Study2. By prospective studies, PBMCs from10cases of generalized MG patients before and after receving LPE therapy and10people physically healthy were taken, the expressions of AChR+IL-21R+B cells and AChR+IgG+B cells were detected by flow cytometry, the levels of peripheral serum IL-21and anti-AChR-Ab were detected by ELISA. QMG scores was performed before and the third day after treatment in MG patients, the blood RT and immune full set before and after treatment were tested. The correlationships among them were further analyzed. All statistics were dealed with SPSS11.7software package.Results:Study1(1) In the QMG score≥10points group, the hospital stays of patients receiving LPE therapy was shorter than the patients receiving GP therapy (14.16±4.77days,17.33±9.43days), the difference was statistically significant (P<0.05); In the QMG score<10group, the hospital stays of patients receiving LPE therapy was longer than the patients receiving GP therapy (20.5±8.5days,15.8±8.81days), but the difference was not statistically significant (P<0.05).(2) In the QMG score≥10group, the tracheostomy rate during hospitalization in patients receiving LPE therapy was0%, and the tracheostomy rate during hospitalization in patients receiving GP therapy was34.78%, the tracheostomy rate of LPE therapy group was significantly lower than GP therapy group, the difference was statistically significant (P<0.01); In the QMG score<10group, the tracheostomy rate during hospitalization in patients receiving LPE therapy was0%, and the tracheostomy rate during hospitalization in patients receiving GP therapy was12.5%, the tracheostomy rate of LPE therapy group was lower than GP therapy group, the difference was statistically significant (P<0.05).(3) In the QMG score≥10points group, when QMG score improved eight points, the hospital stays of patients receiving LPE therapy was shorter than the patients receiving GP therapy (6.85±2.97days,10.15±5.73days), the difference was statistically significant (P <0.05); In the QMG score<10group, when QMG score improved four points, the hospital stays of patients receiving LPE therapy was longer than the patients receiving GP therapy (16.32±7.13days12.24±6.65days), but the difference was not statistically significant (P <0.05).Study2(1) After LPE therapy, the QMG score of MG patients was lower than the before(17.60±4.28points,7.00±2.03points), the difference was statistically significant (P<0.05). (2) Compared with before LPE therapy, the serum levels of IgG、 IgM、IgA、C3、C4in MG patients after therapy was lower (respectively,10.10±6.16g/L,8.82±3.13g/L;2.34±0.59g/L,1.96±0.86g/L;1.11±0.34g/L,0.92±0.32g/L;0.82±0.15g/L,0.68±0.97g/L;0.19±0.06g/L,0.15±0.05g/L), the difference were statistically significant (P<0.05)(3) After LPE therapy, the proportion and numbers of PBMCs in MG patients were lower than the before (respectively,39.81±8.02%,32.68±8.33%;3.27±0.66×109/L,2.69±0.68×109/L), the proportion and numbers of monocytes were lower than the before (respectively,8.98±2.68%,5.77±2.20%;0.68±0.22×109/L,0.44±0.17×109/L), the difference were statistically significant (P<0.05)(4) Before LPE therapy, the serum anti-AChR-Ab levels of MG patients was higher than the normal controls (NCs)(273±146pmol/L,53±17pmol/L), the difference was statistically significant (p<0.05). After therapy, the serum AChR-Ab levels in MG patients (157±81pmol/L) was lower than the before but higher than the NCs, the difference were statistically significant (p<0.05).(5) Before LPE therapy, the serum IL-21levels of MG patients was higher than the NCs (34.95±4.38pg/ml,13.47±5.64pg/ml), the difference was statistically significant (p<0.01); After therapy, the serum IL-21levels (18.41±5.40pg/ml) was significantly lower than the before(p<0.05), but the difference wasn’t statistically significant compared with the NCs(p>0.05).(6) Before LPE therapy, the expression of AChR+B cells in MG patients was higher than the NCs(1.43±0.75%,0.25±0.13%), the difference was statistically significant (p<0.01); After therapy, the expression of AChR+B cells (0.52±0.27%)was lower than the before but higher than the NCs, the difference were statistically significant (p<0.05).(7) Before LPE therapy, the expression of IL-21R+B cells in MG patients was higher than the NCs (0.31±0.11%,0.13±0.039%), the difference was statistically significant (p<0.01); After therapy, the expression of IL-21R+B cells (0.17±0.065%) was lower than the before, the difference was statistically significant (p<0.05), but the difference wasn’t statistically significant compared with the NCs (p>0.05).(8) Before LPE thepapy, the expression of IL-21R+AChR+B cells in MG patients was higher than the NCs (0.29±0.12%,0.08±0.026%), the difference was statistically significant (p<0.01); After therapy, the expression of IL-21R+AChR+B cells (0.13±0.054%) was significantly lower than the before (p<0.05), but the difference wasn’t statistically significant compared with the NCs(p>0.05).(9) Before LPE therapy, the expression of IgG+B cells in MG patients was higher than the NCs (0.63±0.42%,0.13±0.057%), the difference was statistically significant (p<0.01); After therapy, the expreesion of IgG+B cells (0.36±0.21%) was lower than the before but higher than the NCs, the difference were statistically significant (p<0.05).(10) Before LPE therapy, the expression of IgG+AChR+B cells in MG patients was higher than the NCs (0.61±0.39%,0.031±0.0017%), the difference was statistically significant (p<0.01); After therapy, the expression of IgG+AChR+B cells (0.29±0.18%) was lower than the before but higher than the NCs, the difference were statistically significant (p<0.05).(11) Before LPE therapy, the expressions of AChR+IL-21R+AChR+IgG+B cells in MG patients were significant correlated with the QMG scores (respectively, r=0.775, r=0.793, both p<0.05). The expressions of AChR+、IL-21R+、IgG+B cells and the levels of anti-AChR-Ab、sIL-21、complement、PBMCs、mononuclear cells were not correlated with the QMG scores.(12) After LPE therapy, the expressions of AChR+、IL-21R+AChR+IL-21R+、IgG+、AChR+IgG+B cells and the levels of anti-AChR-A、sIL-21、complement、 PBMCs、mononuclear cells in MG patient were not correlated with the QMG scores.(13) After LPE therapy, the fall of anti-AChR-Ab level in MG patients were significant correlated with the declines of sIL-21 IL-21R+、AChR+IL-21R+B cells,(respectively, r=0.765, r=0.771, r=793, both p<0.05).(14) After LPE therapy, the improvement of QMG scores in MG patients were significant correlated with the declines of AChR-Ab、 sIL-21、complement、mononuclear cells、IL-21R+、AchR+IL-21R+and AChR+IgG+B cells,(respectively, r=0.773, r=0.777, r=0.757, r=0.825, r=0.809, r=0.758, r=0.765, r=879, both p<0.05). The declines of PBMCs、AChR+、IgG+B cells were not significant correlated with the improvement of QMG scores.Conclusion:(1) For those severe MG patients who need to be hospitalized, the effectiveness of LPE is more quickly and safe compared with GP.(2) By lowering serum IgG antibody、complement and IL-21levels, reducing the expressions of AChR+IgG+B cells and AChR+IL-21R+B cells and so on, LPE play its therapeutic effect on the MG. |
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