Martínez-Maza O, Moody D J, Rezai A R, Ellison G W, Myers L W, Tourtellotte W W, Fahey J L
J Clin Immunol. 1987 Mar;7(2):107-13. doi: 10.1007/BF00916004.
Spontaneous immunoglobulin (Ig) secretion by cells from multiple sclerosis (MS) patients (in the progressive phase) treated with monthly pulse doses of cyclophosphamide (CY) (1000-1600 mg/M2) was measured using the protein A plaque assay, to evaluate the effect of CY treatment on B-cell function. Surprisingly, an increase, rather than a decrease, in Ig-secreting cells was seen following CY treatment. CY-treated MS patients averaged 1380 +/- 535 spontaneous total (IgM + G + A) Ig plaque-forming cells (PFC) per 1 X 10(6) peripheral blood mononuclear cells (MNC), measured at 15-22 days after monthly CY administration, while healthy adults had 280 +/- 47 Ig PFC/10(6) MNC, and MS patients not treated with CY had 300 +/- 43 Ig PFC/10(6) MNC. The observed increase was due to an increase in IgG and IgA PFC. PFC levels remained elevated for 4 weeks following CY treatment, decreasing to control levels by 7-8 weeks post-CY. A small increase in serum IgG level was noted after greater than 12 months of pulse CY therapy; no increase was seen in CSF IgG levels. A preferential decrease in the number of CD4+ T cells was also seen in the CY-treated MS patients. We propose that the observed increase in the number of spontaneous Ig PFC was due to the CY-induced disruption of the CD4+ T cell-mediated control of in vivo activated B cells.
采用蛋白A空斑试验测量接受每月一次环磷酰胺（CY）脉冲剂量（1000 - 1600 mg/M²）治疗的（进展期）多发性硬化症（MS）患者细胞的自发免疫球蛋白（Ig）分泌，以评估CY治疗对B细胞功能的影响。令人惊讶的是，CY治疗后Ig分泌细胞数量增加而非减少。在每月给予CY后15 - 22天测量，接受CY治疗的MS患者每1×10⁶外周血单个核细胞（MNC）平均有1380±535个自发总（IgM + G + A）Ig空斑形成细胞（PFC），而健康成年人每10⁶MNC有280±47个Ig PFC，未接受CY治疗的MS患者每10⁶MNC有300±43个Ig PFC。观察到的增加是由于IgG和IgA PFC增加。CY治疗后PFC水平在4周内保持升高，CY治疗后7 - 8周降至对照水平。在脉冲CY治疗超过12个月后，血清IgG水平有小幅升高；脑脊液IgG水平未见升高。在接受CY治疗的MS患者中还观察到CD4⁺T细胞数量优先减少。我们认为观察到的自发Ig PFC数量增加是由于CY诱导的体内活化B细胞的CD4⁺T细胞介导控制的破坏。
