Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders
Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders
复制标题
DOI：
10.1200/jco.2005.02.7938
复制
发表时间：
2006-02-20
影响因子：
45.3
通讯作者：
Ansell, SM
中科院分区：
文献类型：
--
作者：
Novak, AJ;Grote, DM;Ansell, SM
研究目的：血清B淋巴细胞刺激因子（BLyS）水平在许多免疫性疾病模型中升高。因此，我们试图确定B细胞淋巴增生性疾病患者的BLyS水平是否升高，并确定升高的BLyS水平是否与疾病的临床特征相关。（B-CLL; n = 70）或来自在同一机构就诊的年龄和性别匹配的患者（n = 41）。血清BLyS水平测定的酶联免疫吸附试验，和BLyS启动子的测序进行常规方法和证实的限制性片段长度多态性analysis.Results我们发现，升高的BLyS水平更常见于家族性B-CLL患者比散发性B-CLL或正常对照组的个人。由于这种关联，我们对B-CLL患者和正常对照的BLyS启动子进行了测序，并确定了一个多态性位点，-871 C/T。我们发现，与散发性B-CLL患者（30%; P = 0.01）或对照组（24%; P = 0.04）相比，家族性B-CLL患者（4%）中野生型序列的代表性明显不足。此外，使用在BLyS启动子控制下的荧光素酶报告基因，所述BLyS启动子在位置-871处含有C或T，我们发现，在-871位含有T的报告基因构建体的活性增加了2.6倍，结论家族性B-CLL患者血清BLyS水平升高，且BLyS水平升高与T-871在BLyS启动子中。
Purpose Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease.Patients and Methods Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis.Results We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P = .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004).Conclusion Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.