Kowalczyk D, Mytar B, Zembala M
Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow.
J Allergy Clin Immunol. 1997 Oct;100(4):556-62. doi: 10.1016/s0091-6749(97)70150-7.
Transient hypogammaglobulinemia of infancy and isolated IgA deficiency are characterized by normal numbers of circulating B lymphocytes. It is likely that no single abnormality, but rather different factors, may be relevant for the delayed onset of IgG synthesis in transient hypogammaglobulinemia or for the differentiation defect of B cells in IgA deficiency. These factors may include defective production of cytokines or an abnormal response of B cells to various mediators. Alternatively, some cytokines may act as inhibitory factors of B-cell function.
The ability of peripheral blood mononuclear cells from children with proved or probable transient hypogammaglobulinemia (30 patients) and IgA deficiency (15 patients) to secrete several cytokines on stimulation with phytohemagglutinin in vitro was analyzed.
An enhanced production of tumor necrosis factor (TNF)-alpha, TNF-beta, and IL-10 was observed in transient hypogammaglobulinemia; whereas secretion of IL-1, IL-4, and IL-6 was essentially similar in the control and patient groups. Increased frequency of mononuclear cells secreting TNF-alpha was seen in the patient groups. Apart from elevated production of TNF-alpha, no other abnormalities in cytokine synthesis in selective IgA deficiency were observed. In vitro observations showed that exogenously added TNF-alpha and TNF-beta inhibited IgG and IgA secretion by pokeweed mitogen-stimulated mononuclear cells. During follow-up of 10 children, normalization of serum IgG level was associated with a decrease in previously elevated TNF-alpha and TNF-beta production, but IL-10 production remained unchanged.
These results suggest that TNF may be involved in the regulation of IgG and IgA production and can be associated with an arrest of IgG and IgA switch of B cells in hypogammaglobulinemia. The balance between TNF and IL-10 may be important for the normal development of IgG-secreting B cells.
婴儿期短暂性低丙种球蛋白血症和孤立性IgA缺乏症的特征是循环B淋巴细胞数量正常。在婴儿期短暂性低丙种球蛋白血症中，IgG合成延迟或在IgA缺乏症中B细胞分化缺陷，可能不是单一异常，而是不同因素起作用。这些因素可能包括细胞因子产生缺陷或B细胞对各种介质的异常反应。另外，一些细胞因子可能作为B细胞功能的抑制因子。
分析了确诊或疑似婴儿期短暂性低丙种球蛋白血症患儿（30例）和IgA缺乏症患儿（15例）的外周血单个核细胞在体外经植物血凝素刺激后分泌多种细胞因子的能力。
在婴儿期短暂性低丙种球蛋白血症中观察到肿瘤坏死因子（TNF）-α、TNF-β和IL-10的产生增加；而对照组和患者组中IL-1、IL-4和IL-6的分泌基本相似。患者组中分泌TNF-α的单个核细胞频率增加。除了TNF-α产生增加外，在选择性IgA缺乏症中未观察到细胞因子合成的其他异常。体外观察表明，外源性添加的TNF-α和TNF-β抑制了商陆有丝分裂原刺激的单个核细胞分泌IgG和IgA。在对10名儿童的随访中，血清IgG水平正常化与之前升高的TNF-α和TNF-β产生减少相关，但IL-10产生保持不变。
这些结果表明，TNF可能参与IgG和IgA产生的调节，并可能与低丙种球蛋白血症中B细胞的IgG和IgA类别转换停滞有关。TNF和IL-10之间的平衡可能对分泌IgG的B细胞的正常发育很重要。
