Maloney S, Smith A, Furst D E, Myerson D, Rupert K, Evans P C, Nelson J L
Immunogenetics Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
J Clin Invest. 1999 Jul;104(1):41-7. doi: 10.1172/JCI6611.
Recent studies indicate that fetal cells persist in maternal blood for decades after pregnancy. Maternal cells are known to engraft and persist in infants with immunodeficiency, but whether maternal cells persist long-term in immunocompetent offspring has not specifically been investigated. We developed sensitive human leukocyte antigen-specific (HLA-specific) PCR assays and targeted nonshared maternal HLA genes to test for persistent maternal microchimerism in subjects with scleroderma and in healthy normal subjects. Nonshared maternal-specific DNA was found in 6 of 9 scleroderma patients. In situ hybridization with double labeling for X and Y chromosome-specific sequences revealed female cells in peripheral blood samples from 2 male scleroderma patients. HLA-specific PCR also frequently revealed persistent maternal microchimerism in healthy control subjects. The mean age of all subjects with maternal microchimerism was 28 years (range: 9-49 years). With few exceptions, mothers of subjects with persistent maternal microchimerism were HLA incompatible with subjects for class I and class II alleles. These results clearly indicate that HLA-disparate maternal cells can persist in immunocompetent offspring well into adult life. The biological significance of maternal microchimerism and whether it might contribute to autoimmune disease requires further investigation.
近期研究表明,孕期结束后,胎儿细胞可在母血中持续存在数十年。已知母体细胞可植入免疫缺陷婴儿体内并长期存在,但母体细胞在免疫功能正常的后代中是否长期存在尚未得到专门研究。我们开发了敏感的人类白细胞抗原特异性(HLA特异性)PCR检测方法,并针对非共享的母体HLA基因,以检测硬皮病患者和健康正常受试者中持续存在的母体微嵌合体。在9例硬皮病患者中,有6例检测到非共享的母体特异性DNA。对X和Y染色体特异性序列进行双重标记的原位杂交显示,2例男性硬皮病患者的外周血样本中存在女性细胞。HLA特异性PCR在健康对照受试者中也经常检测到持续存在的母体微嵌合体。所有存在母体微嵌合体的受试者的平均年龄为28岁(范围:9 - 49岁)。除少数例外,存在持续母体微嵌合体的受试者的母亲在I类和II类等位基因上与受试者HLA不匹配。这些结果清楚地表明,HLA不同的母体细胞可在免疫功能正常的后代中持续存在至成年期。母体微嵌合体的生物学意义以及它是否可能导致自身免疫性疾病需要进一步研究。