Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma.
Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma.
复制标题
胃粘膜相关淋巴组织 B 细胞淋巴瘤幽门螺杆菌感染治愈后持续的体细胞突变和克隆扩增。
DOI：
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复制
发表时间：
1998
影响因子：
45.3
通讯作者：
A. Neubauer
中科院分区：
文献类型：
--
作者：
C. Thiede;B. Alpen;A. Morgner;M. Schmidt;M. Ritter;G. Ehninger;M. Stolte;E. Bayerdörffer;A. Neubauer
目的
虽然大多数胃低级别粘膜相关淋巴组织(MALT)B细胞淋巴瘤患者在幽门螺杆菌感染治愈后胃镜和组织学完全缓解，但在许多患者中，聚合酶链式反应(PCR)仍可在胃粘膜中检测到单克隆性B细胞。本研究探讨了胃MALT淋巴瘤患者在根除幽门螺杆菌后，淋巴瘤免疫球蛋白VH(IgVH)序列是否保持稳定。
患者和方法
对8例EI期患者在根除Hp前后不同时间点的临床资料进行分析。从胃活检组织提取的DNA中扩增出IgVH基因后，克隆单克隆性聚合酶链式反应产物，对每个患者的多个克隆(43~105个)进行测序。
结果
所有淋巴瘤VH序列均检测到突变，提示淋巴瘤B细胞来源于生发中心或生发后中心。在8名患者中，有5名患者在诊断时或随访期间观察到克隆异质性。共有和非共有突变的系谱分析显示，在5名表现出克隆不稳定的患者中，有4名患者在根除幽门螺杆菌后体细胞突变过程仍在进行。在根除幽门螺杆菌完全有效的四名患者中，有三名观察到正在进行的突变，但在四名无反应或部分有效的患者中，只有一名患者观察到了持续的突变。
结论
在低级别胃MALT淋巴瘤中，在治疗去除潜在的刺激H Pylori后，可以检测到正在进行的体细胞高突变和抗原选择的过程。这些数据指出了驱动这种疾病的未知抗原的相关性。此外，他们还挑战了仅通过根除幽门螺杆菌就可以治愈这些淋巴瘤的观点。
PURPOSE
Although most patients with primary gastric low-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclonal B cells in the gastric mucosa. The present study asked whether the lymphoma immunoglobulin VH (IgVH) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication.
PATIENTS AND METHODS
Eight patients with stage EI disease treated with H pylori eradication were analyzed before and at different time points after the cure of the infection. After the amplification of IgVH genes from DNA extracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105) were sequenced per patient.
RESULTS
Mutations were detected in all lymphoma VH sequences, which suggested germinal center or postgerminal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagnosis or during follow-up. Genealogical analysis of shared and unshared mutations showed that the process of somatic mutations was ongoing after H pylori eradication in four of the five patients who showed clonal instability. Ongoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients who did not respond or who partially responded.
CONCLUSION
In low-grade gastric MALT lymphomas, an ongoing process of somatic hypermutation and antigen selection can be detected after the therapeutic removal of the underlying stimulus H pylori. These data point to the relevance of yet unknown antigens that drive this disease. In addition, they challenge the view that these lymphomas may be cured solely by the eradication of H pylori.
人 Ig 重链 DIR 基因的分子特征。
DOI：
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发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Sanz,I;Wang,SS;Meneses,G;Fischbach,M
通讯作者：
Fischbach,M
DOI：
10.1016/0167-5699(94)90175-9
发表时间：
1994-08-01
期刊：
IMMUNOLOGY TODAY
影响因子：
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作者：
CHANG, B;CASALI, P
通讯作者：
CASALI, P