Langer-Gould Annette, Gupta Rohit, Huang Stella, Hagan Adam, Atkuri Kondala, Leimpeter Amethyst D, Albers Kathleen B, Greenwood Eleni, Van Den Eeden Stephen K, Steinman Lawrence, Nelson Lorene M
Department of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Arch Neurol. 2010 Jan;67(1):51-7. doi: 10.1001/archneurol.2009.304.
To determine whether fluctuations in functional T-cell subsets can explain why multiple sclerosis (MS) relapses decline during pregnancy and increase in the postpartum period.
Case-control study.
Kaiser Permanente Northern California and Stanford University.
Twenty-six pregnant women with MS and 24 age-matched, pregnant controls. Intervention We prospectively followed up the pregnant women with MS and the age-matched, pregnant controls; conducted structured interviews; and collected peripheral blood mononuclear cells during each trimester and 2, 4, 6, 9, and 12 months post partum.
Sixteen functional cell types, including interferon-gamma (IFN-gamma)- and tumor necrosis factor-producing T-cell subsets, were measured using multicolor flow cytometry. Since these cell types may also fluctuate with pregnancy, lactational amenorrhea, or MS treatment, the data were analyzed taking into account these factors.
Fifteen women with MS (58%) had relapses during the postpartum year. CD4(+)IFN-gamma-producing cells fluctuated with MS relapses, declining during pregnancy in women with MS (P < .001) and continuing to decline after parturition in women with relapses (P = .001), yet rising or remaining stable in women with nonrelapsing MS or healthy pregnant women. Lactational amenorrhea was associated with a rise in CD4(+)IFN-gamma-producing cells in women with MS (P = .009). In contrast, CD4(+) tumor necrosis factor-producing cells decreased during lactational amenorrhea in all groups of women and, once this was taken into account, obscured any relationship to MS relapses. CD8(+)IFN-gamma-producing cells were elevated in women with MS throughout the study (P < .001) but did not fluctuate with relapses.
Our findings suggest that a decline in circulating CD4(+)IFN-gamma-producing cells leads to postpartum MS relapses. Our findings also suggest that the decline in these cells may begin during late pregnancy and that lactational amenorrhea induced by exclusive breastfeeding may be able to interrupt this process.
确定功能性T细胞亚群的波动是否能解释为何多发性硬化症（MS）在孕期复发减少而在产后复发增加。
病例对照研究。
北加利福尼亚凯撒医疗集团和斯坦福大学。
26名患有MS的孕妇和24名年龄匹配的怀孕对照者。干预措施：我们对患有MS的孕妇和年龄匹配的怀孕对照者进行前瞻性随访；进行结构化访谈；并在每个孕期以及产后2、4、6、9和12个月收集外周血单个核细胞。
使用多色流式细胞术检测16种功能性细胞类型，包括产生干扰素-γ（IFN-γ）和肿瘤坏死因子的T细胞亚群。由于这些细胞类型也可能随怀孕、哺乳期闭经或MS治疗而波动，因此在分析数据时考虑了这些因素。
15名患有MS的女性（58%）在产后一年内复发。产生CD4(+)IFN-γ的细胞随MS复发而波动，在患有MS的女性孕期下降（P <.001），复发的女性产后继续下降（P =.001），而在无复发的MS女性或健康孕妇中则上升或保持稳定。哺乳期闭经与患有MS的女性产生CD4(+)IFN-γ的细胞增加有关（P =.009）。相比之下，在所有女性组中，产生CD4(+)肿瘤坏死因子的细胞在哺乳期闭经期间减少，一旦考虑到这一点，就掩盖了与MS复发的任何关系。在整个研究过程中，患有MS的女性中产生CD8(+)IFN-γ的细胞升高（P <.001），但不随复发而波动。
我们的研究结果表明，循环中产生CD4(+)IFN-γ的细胞减少会导致产后MS复发。我们的研究结果还表明，这些细胞的减少可能在妊娠晚期开始，并且纯母乳喂养引起的哺乳期闭经可能能够中断这一过程。
