特发性血小板减少性紫癜患者外周血及脾脏单个核细胞中的BAFF和BAFF-R

BAFF and BAFF-R of peripheral blood and spleen mononuclear cells in idiopathic thrombocytopenic purpura.

作者信息

Zhou Zeping, Chen Zhenping, Li Hongqiang, Chen Xiaoli, Xu Jianhui, Gu Dongsheng, Du Weiting, Zheng Cuiling, Zhang Lei, Huang Ying, Ren Qian, Yang Renchi

机构信息

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, PR China.

出版信息

Autoimmunity. 2009 Feb;42(2):112-9. doi: 10.1080/08916930802397848.

DOI:10.1080/08916930802397848

PMID:19005881

Abstract

BAFF (B-cell activating factor belonging to the TNF family) is an essential component of B-cell homeostasis, and is required for the normal survival and development of B cells. To further explore the role of this cytokine in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), BAFF/BAFF-R (one of receptors of BAFF) expression levels were determined and the correlation between the clinical parameters and the BAFF expression levels was analyzed. A total of 57 patients with ITP were enrolled and 25 age and sex-matched healthy volunteers served as controls. Serum was obtained from 41 patients with ITP and 22 healthy volunteers and was analyzed with a commercial human soluble BAFF (sBAFF) ELISA kit. BAFF and BAFF-R mRNA expression of peripheral blood (PB) (n = 42) and splenocytes (SP) (n = 8) mononuclear cells (MNC) were determined by real-time quantitative PCR. The SPMNC of normal controls came from three hereditary spherocytosis patients who underwent splenectomy. The untreated patients with ITP had higher serum BAFF levels (Median 1430 pg/ml, Range: 534-5787 pg/ml) than those of normal controls (Median 1120 pg/ml, Range: 640-2376 pg/ml, p = 0.006) and treated ITP group (Median 662 pg/ml, Range 267-1265 pg/ml, p = 0.000). On the other hand, serum BAFF levels of treated patients with ITP were lower than those of normal controls (p = 0.001). There was a weak correlation (the Pearson correlation coefficient is - 0.242) between platelet count and BAFF (p = 0.064). However, BAFF levels did not correlate with platelet associated immunoglobulin or immunoglobulin levels. Moreover, the serum BAFF levels were not statistically different between acute and chronic ITP (p = 0.841). PBMNC of ITP had higher BAFF but not BAFF-R mRNA expression than that of normal controls. BAFF mRNA expression of SPMNC had a positive correlation with BAFF-R in ITP patients but not in PBMNC of normal controls and untreated ITP patients. The BAFF-R mRNA expression of SPMNC was shown to be 15.29 times higher than that of PBMNC in ITP. BAFF might contribute to autoimmunity and disease development in ITP. However, BAFF serum level must be carefully considered as a surrogate marker of disease activity in ITP.

摘要

BAFF（B细胞活化因子，属于肿瘤坏死因子家族）是B细胞稳态的重要组成部分，是B细胞正常存活和发育所必需的。为了进一步探讨这种细胞因子在特发性血小板减少性紫癜（ITP）发病机制中的作用，测定了BAFF/BAFF-R（BAFF的受体之一）的表达水平，并分析了临床参数与BAFF表达水平之间的相关性。共纳入57例ITP患者，25例年龄和性别匹配的健康志愿者作为对照。采集41例ITP患者和22例健康志愿者的血清，用商用人类可溶性BAFF（sBAFF）ELISA试剂盒进行分析。通过实时定量PCR测定外周血（PB）（n = 42）和脾细胞（SP）（n = 8）单个核细胞（MNC）中BAFF和BAFF-R mRNA的表达。正常对照的SPMNC来自3例接受脾切除术的遗传性球形红细胞增多症患者。未经治疗的ITP患者血清BAFF水平（中位数1430 pg/ml，范围：534 - 5787 pg/ml）高于正常对照（中位数1120 pg/ml，范围：640 - 2376 pg/ml，p = 0.006）和治疗后的ITP组（中位数662 pg/ml，范围267 - 1265 pg/ml，p = 0.000）。另一方面，治疗后的ITP患者血清BAFF水平低于正常对照（p = 0.001）。血小板计数与BAFF之间存在弱相关性（Pearson相关系数为 - 0.242）（p = 0.064）。然而，BAFF水平与血小板相关免疫球蛋白或免疫球蛋白水平无关。此外，急性和慢性ITP患者的血清BAFF水平无统计学差异（p = 0.841）。ITP患者的PBMNC中BAFF mRNA表达高于正常对照，但BAFF-R mRNA表达无差异。ITP患者SPMNC中BAFF mRNA表达与BAFF-R呈正相关，但正常对照和未经治疗的ITP患者的PBMNC中无此相关性。在ITP中，SPMNC的BAFF-R mRNA表达比PBMNC高15.29倍。BAFF可能在ITP的自身免疫和疾病发展中起作用。然而，BAFF血清水平作为ITP疾病活动的替代标志物必须谨慎考虑。