Aukrust P, Lien E, Kristoffersen A K, Müller F, Haug C J, Espevik T, Frøland S S
Medical Department A, National Hospital, University of Oslo, Norway.
Blood. 1996 Jan 15;87(2):674-81.
In patients with common variable immunodeficiency (CVI), we have previously defined a subgroup of patients (CVIHyper) characterized by decreased numbers of CD4+ lymphocytes in peripheral blood, splenomegaly, and persistent immune activation in vivo, particularly of monocytes/macrophages. To further characterize this hyperactivity, parameters of activation of the tumor necrosis factor (TNF) system (TNF alpha and soluble TNF receptors [sTNFRs]) were measured in 24 patients with CVI and 20 healthy controls. Patients with CVI had significantly higher serum levels of TNF alpha and both types of sTNFRs, with the highest levels in the CVIHyper subgroup. In vitro, peripheral blood mononuclear cells (PBMC) and purified monocytes from CVIHyper patients spontaneously released significantly higher levels, and, after lipopolysaccharide (LPS) stimulation, significantly lower levels of TNF alpha and soluble p75-TNFR than cells from both other CVI patients and healthy controls. CVIHyper patients also had significantly higher TNF alpha:sTNFRs ratios in both serum and in unstimulated PMBC supernatants. The present study demonstrates persistent in vivo activation of the TNF system in CVI, particularly in the CVIHyper subgroup. This activation may contribute to the pathogenesis of both clinical and immunologic manifestations in CVI.
在常见变异型免疫缺陷（CVI）患者中，我们之前定义了一个患者亚组（CVIHyper），其特征为外周血中CD4 +淋巴细胞数量减少、脾肿大以及体内持续的免疫激活，尤其是单核细胞/巨噬细胞的免疫激活。为了进一步描述这种高活性，我们检测了24例CVI患者和20例健康对照者肿瘤坏死因子（TNF）系统（TNFα和可溶性TNF受体[sTNFRs]）的激活参数。CVI患者的血清TNFα水平以及两种类型的sTNFRs水平均显著更高，其中CVIHyper亚组的水平最高。在体外，CVIHyper患者的外周血单个核细胞（PBMC）和纯化的单核细胞自发释放的TNFα和可溶性p75 - TNFR水平显著更高，而在脂多糖（LPS）刺激后，其释放水平显著低于其他CVI患者和健康对照者的细胞。CVIHyper患者血清和未刺激的PBMC上清液中的TNFα:sTNFRs比值也显著更高。本研究表明CVI中TNF系统存在持续的体内激活，尤其是在CVIHyper亚组中。这种激活可能有助于CVI临床和免疫表现的发病机制。
