Loss of circulating CD27+ memory B cells and CCR4+ T cells occurring in association with elevated EBV loads in XLP patients surviving primary EBV infection
Loss of circulating CD27+ memory B cells and CCR4+ T cells occurring in association with elevated EBV loads in XLP patients surviving primary EBV infection
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DOI：
10.1182/blood-2003-07-2525
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发表时间：
2004-03-01
期刊：
影响因子：
20.3
通讯作者：
de Bracco, MM
中科院分区：
文献类型：
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作者：
Malbran, A;Belmonte, L;de Bracco, MM
对X连锁淋巴增殖性疾病（XLP）患者进行详细的纵向研究可能会增进我们对导致XLP患者发生淋巴瘤和低丙种球蛋白血症的免疫缺陷的理解。我们描述了在一名新感染但在其他方面健康的携带者（患者9）中，在2年期间观察到的免疫球蛋白浓度、淋巴细胞亚群以及爱泼斯坦 - 巴尔病毒（EBV）载量的渐进性变化。我们将这些发现与患者的兄弟（患有低丙种球蛋白血症和XLP，患者4）的情况进行了比较。患者9在急性EBV感染期间，免疫球蛋白G（IgG）、IgM和IgA浓度升高，但此后它们稳定下降至符合低丙种球蛋白血症的浓度，在感染5个月后达到平台期。在这两名患者中，CD19⁺ B淋巴细胞比例均保持低于3%，B细胞记忆区室（CD27⁺CD19⁺/CD19⁺）收缩至20%（正常范围为32% - 56%）。T淋巴细胞亚群表现为CD4⁺ T细胞计数减少以及CD8⁺ T细胞永久性扩增。有趣的是，CXCR3记忆性T辅助细胞1（Tₕ1）细胞扩增，而CCR4⁺ Tₕ2淋巴细胞减少，这表明记忆性T细胞亚群的异常偏移可能导致抗体合成减少。尽管CD3⁺CD8⁺淋巴细胞数量增加，但两名患者的EBV载量均升高，却没有单核细胞增多症、淋巴增殖性疾病或淋巴瘤的明显临床症状。（C）2004年美国血液学会版权所有。
Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subsets, and Epstein-Barr virus (EBV) loads occurring in a 2-year period in a newly infected, but otherwise healthy, carrier (patient 9). We compare these findings with those observed in the patient's brother, who had hypogammaglobulinemia and XLP (patient 4). Immunoglobulin G (IgG), IgM, and IgA concentrations increased in patient 9 during acute EBV infection, but thereafter they decreased steadily to concentrations consistent with hypogammaglobulinemia, reaching a plateau 5 months after infection. In both patients, CD19(+) B-lymphocyte rates remained lower than 3%, with a contraction of the B-cell memory compartment (CD27(+) CD19(+)/CD19(+)) to 20% (normal range, 32%-56%). T-lymphocyte subpopulations showed a reduction in CD4(+) T-cell counts and a permanent CD8(+) T-cell expansion. Interestingly, CXCR3 memory T(H)1 cells were expanded and CCR4(+) T(H)2 lymphocytes were reduced, suggesting that abnormal skewing of memory T-cell subsets might contribute to reduced antibody synthesis. Despite an expanded number of CD3(+)CD8(+) lymphocytes, increased EBV loads occurred in both patients without overt clinical symptoms of mononucleosis, lymphoproliferative disease, or lymphoma. (C) 2004 by The American Society of Hematology.