Objective: To investigate the IGHV mutational status and its differences from Caucasian in splenic marginal zone lymphoma (SMZL). Methods: A retrospective study on 40 SMZL cases were performed to detect the V-D-J sequence of IGHV by plasmid cloning sequencing, comparing the data with the most homologous germ line V sequence in database, identifying the stereotype of patients through cluster analysis and alignment. The clinical and laboratory characteristics were compared between the patients with IGHV mutation and without mutations. Results: In SMZL patients, the proportion of IGHV mutations was 75%, consistent with data from Caucasian. In V region, the usage of V3-23 subtype was lower in Chinese patients compared with Caucasian (2.6% vs 18.0%, P=0.006), whereas the V2-70 subtype was used with high proportion (10.3% vs 0.8%, P=0.002). In D region, the D2-21 and D6-13 gene were used frequently (17.9% vs 2.3%, P<0.001; 12.8% vs 3.8%, P=0.046). One new stereotype was found, and the SMZL-biased V1-2 gene was mostly used (25.6%). The levels of IgG and IgA were significantly increased in IGHV without mutations as compared with mutations [10.70 (5.28-15.50) g/L vs 12.90 (7.71-23.50) g/L, 1.06 (0.21-3.13) g/L vs 1.66 (0.81-2.93) g/L, P=0.038, 0.040]. The only two 17p deletion patients were IGHV without mutaions. The progression free survival (PFS) was significantly prolonged in IGHV mutations (P=0.009), and there was no significant difference regarding to the overall survival between the two subgroups (P=0.430). Conclusion: The proportion of IGHV mutaions was similar to the data in Caucasian. There was disparity in the usage of V and D regions between Chinese and Caucasian, and the SMZL-biased V1-2 gene were used more frequently in Chinese patients. One new stereotype was identified. In the IGHV without mutations group, the levels of IgG and IgA were significantly increased.
目的: 研究脾边缘区淋巴瘤（SMZL）患者免疫球蛋白重链可变区（IGHV）基因突变状态及典型模式的分布情况，并与国外报道的数据进行对比，以探讨其差异。
方法: 对40例SMZL患者资料进行回顾性分析。采用克隆测序法检测IGHV的VDJ序列并进行比对及聚类分析，明确是否存在B细胞受体的典型模式，分析IGHV突变患者与未突变患者的临床特征。
结果: 40例患者中，IGHV突变者30例（75.0%），未突变者10例（25.0%），两者比例与国外报道相当。在V区基因，V2-70的使用频率高于国外报道（10.3％对0.8%，P=0.002），而V3-23明显减低（2.6％对18.0%，P=0.006）。在D区基因中，D2-21和D6-13均高于国外报道（17.9％对2.3%，12.8%对3.8%，P值分别为0.000、0.046）。40例患者中发现1对新的典型模式，同时SMZL特异性的V1-2基因使用频率也最高（25.6%）。与IGHV突变组相比，未突变组患者的IgG、IgA表达水平显著增高[10.70（5.28~15.50）g/L对12.90 (7.71~23.50) g/L，1.06（0.21~3.13) g/L对1.66 (0.81~2.93) g/L，P值分别为0.038、0.040）]，2例17p缺失患者的IGHV均呈未突变状态。与IGHV未突变组相比，突变组患者的无进展生存期显著延长（P=0.009），但总生存期差异无统计学意义（P=0.430）。
结论: 在SMZL患者中，IGHV突变与未突变患者比例与国外报道相当，但V区和D区基因的使用频率仍存在差异，而且V1-2基因的使用呈现疾病特异性，同时发现1例新的典型模式。IGHV突变可降低患者的IgG、IgA表达水平。