Dai Xing, Wu Yu-Jing, Jia Xiao-Yi, Chang Yan, Wu Hua-Xun, Wang Chun, Wei Wei
a Institute of Clinical Pharmacology , Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of the Education Ministry of China, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine , Hefei , People's Republic of China.
Hematology. 2019 Dec;24(1):544-551. doi: 10.1080/16078454.2019.1642553.
Immunoglobulin D (IgD) levels are often elevated in patients with autoimmune diseases. However, the oncogenic activities of IgD and IgD receptor (IgDR) in diffuse large B-cell lymphoma (DLBCL) have not been reported in detail. Therefore, we aimed to investigate the expression of IgD and IgDR in patients with DLBCL. Membrane IgD (mIgD) and IgDR expression in tissue samples was analyzed using IHC, mIgD and IgDR expression on peripheral blood mononuclear cells (PBMCs) was analyzed by FCM, and secreted IgD (sIgD) level was analyzed by ELISA. Fisher's exact test and Spearman correlation analysis were used to evaluate the relationship between IgD, IgDR, and clinical parameters. The pathological lymph nodes of 34 patients with DLBCL were studied, and mIgD and IgDR expression was found in 16 and 19 patients. mIgD and IgDR expression was upregulated in patients with DLBCL and mIgD expression was significantly associated with IgDR expression. Further correlation analysis showed that mIgD expression was correlated with serum β-MG level and Hans algorithm as germinal center B (GCB), whereas IgDR expression correlated with serum LDH level, IPI score and GCB. ELISA showed that sIgD level was significantly increased in DLBCL patients and it correlated with serum β-MG and LDH levels. FCM showed that mIgD and IgDR expression in PBMCs of patients with DLBCL was significantly higher than that in healthy controls. Our findings suggest that overexpression of IgD and IgDR is an abnormal activation state in DLBCL.
自身免疫性疾病患者的免疫球蛋白D（IgD）水平通常会升高。然而，IgD和IgD受体（IgDR）在弥漫性大B细胞淋巴瘤（DLBCL）中的致癌活性尚未见详细报道。因此，我们旨在研究DLBCL患者中IgD和IgDR的表达情况。使用免疫组织化学（IHC）分析组织样本中膜IgD（mIgD）和IgDR的表达，通过流式细胞术（FCM）分析外周血单个核细胞（PBMC）上mIgD和IgDR的表达，并通过酶联免疫吸附测定（ELISA）分析分泌型IgD（sIgD）水平。采用Fisher精确检验和Spearman相关性分析来评估IgD、IgDR与临床参数之间的关系。对34例DLBCL患者的病理淋巴结进行了研究，发现16例和19例患者中有mIgD和IgDR表达。DLBCL患者中mIgD和IgDR表达上调，且mIgD表达与IgDR表达显著相关。进一步的相关性分析表明，mIgD表达与血清β-微球蛋白（β-MG）水平及生发中心B（GCB）型的Hans分类法相关，而IgDR表达与血清乳酸脱氢酶（LDH）水平、国际预后指数（IPI）评分和GCB相关。ELISA显示，DLBCL患者的sIgD水平显著升高，且与血清β-MG和LDH水平相关。FCM显示，DLBCL患者PBMC中mIgD和IgDR的表达明显高于健康对照。我们的研究结果表明，IgD和IgDR的过表达是DLBCL中的一种异常激活状态。
