Gratama J W, Oosterveer M A, Lepoutre J M, van Rood J J, Zwaan F E, Vossen J M, Kapsenberg J G, Richel D, Klein G, Ernberg I
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Transplantation. 1990 Apr;49(4):725-30. doi: 10.1097/00007890-199004000-00014.
We have shown in two allogeneic bone marrow transplant recipients that Epstein-Barr virus can be eradicated by the BMT procedure or its complications, and that these patients are susceptible to infection with a new EBV strain. This conclusion was based on a combination of EBV serology and virus strain identification ("Ebnotyping," using the size variations of 5 EBV nuclear antigens). In the present study, we conducted a serological survey of EBV infection in 153 marrow graft recipients and their donors. Ten patients who were positive for IgG antibodies against EBV viral capsid antigens prior to BMT became completely seronegative at a median of 197 days post-BMT (range 106-320 days). Four of these patients, who had received seronegative marrow, remained seronegative during prolonged periods (222 to 2105 days). Six patients had received seropositive marrow. Two of them remained seronegative during their subsequent periods of follow-up (895 and 1437 days). An additional 10 patients showed a 100-fold or greater decrease in VCA IgG antibody titers. Their titers reached a nadir of 10 (the lower limit of positive) at a median of 134 days post BMT (range 83-386 days). The serological patterns of the above 20 patients were particularly frequent among patients with chronic graft-versus-host disease; 12 of 20 patients with decreasing VCA titers (60%) developed chronic GVHD versus only 22 of 73 patients with stable or increasing VCA titers (30%). These results suggest that GVHD may contribute to the elimination of residual EBV-carrying recipient cells. Establishment of EBV-carrying lymphoblastoid cell lines (LCL) was attempted in 60 donor-recipient pairs whose cryopreserved peripheral blood mononuclear cells were available. LCL were established from 18 of 51 EBV-seropositive marrow donors and 10 of 57 seropositive recipients prior to BMT. The same EBV strain was detected in 4 of the 6 cases in which LCL could be established from both the donor and the recipient prior to BMT. The persistence of the original EBV strain was demonstrated in a recipient of a T cell-depleted graft who showed only transient hematological recovery and no GVHD, and was associated with the persistence of B cells of recipient origin.
我们在两名异基因骨髓移植受者中发现，爱泼斯坦-巴尔病毒（EBV）可通过骨髓移植手术或其并发症被清除，且这些患者易感染新的EBV毒株。这一结论是基于EBV血清学和病毒毒株鉴定（“Ebnotyping”，利用5种EBV核抗原的大小差异）得出的。在本研究中，我们对153名骨髓移植受者及其供者进行了EBV感染的血清学调查。10名在骨髓移植前针对EBV病毒衣壳抗原的IgG抗体呈阳性的患者，在骨髓移植后中位197天（范围106 - 320天）时完全转为血清阴性。其中4名接受了血清阴性骨髓的患者，在较长时间内（222至2105天）一直保持血清阴性。6名患者接受了血清阳性骨髓。其中2名在随后的随访期间（895天和1437天）一直保持血清阴性。另外10名患者的VCA IgG抗体滴度下降了100倍或更多。他们的滴度在骨髓移植后中位134天（范围83 - 386天）时降至最低点10（阳性下限）。上述20名患者的血清学模式在慢性移植物抗宿主病患者中尤为常见；20名VCA滴度下降的患者中有12名（60%）发生了慢性移植物抗宿主病，而73名VCA滴度稳定或升高的患者中只有22名（30%）发生了慢性移植物抗宿主病。这些结果表明，移植物抗宿主病可能有助于清除残留的携带EBV的受者细胞。我们尝试在60对供者 - 受者中建立携带EBV的淋巴母细胞系（LCL），这些供者 - 受者有冷冻保存的外周血单个核细胞。在51名EBV血清阳性的骨髓供者中有18名以及57名血清阳性的受者中有10名在骨髓移植前建立了LCL。在6例骨髓移植前供者和受者都能建立LCL 的病例中，有4例检测到相同的EBV毒株。在一名接受T细胞去除的移植物的受者中证实了原始EBV毒株的持续存在，该受者仅表现出短暂的血液学恢复且无移植物抗宿主病，并与受者来源的B细胞持续存在有关。
