Clinical Allergy Research Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
PLoS One. 2011;6(7):e22202. doi: 10.1371/journal.pone.0022202. Epub 2011 Jul 13.
The TNF family cytokines BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand) are crucial survival factors for B-cell development and activation. B-cell directed treatments have been shown to improve atopic eczema (AE), suggesting the involvement of these cytokines in the pathogenesis of AE. We therefore analyzed the expression of these TNF cytokines in AE, seborrheic eczema (SE) and healthy controls (HC). The serum/plasma concentration of BAFF, APRIL and a close TNF member TWEAK (TNF-like weak inducer of apoptosis) was measured by ELISA. The expression of these cytokines and their receptors in skin was analyzed by quantitative RT-PCR and immunofluorescence. Unlike other inflammatory diseases including autoimmune diseases and asthma, the circulating levels of BAFF, APRIL and TWEAK were not elevated in AE or SE patients compared with HCs and did not correlate with the disease severity or systemic IgE levels in AE patients. Interestingly, we found that the expression of these cytokines and their receptors was altered in positive atopy patch test reactions in AE patients (APT-AE) and in lesional skin of AE and SE patients. The expression of APRIL was decreased and the expression of BAFF was increased in eczema skin of AE and SE, which could contribute to a reduced negative regulatory input on B-cells. This was found to be more pronounced in APT-AE, the initiating acute stage of AE, which may result in dysregulation of over-activated B-cells. Furthermore, the expression levels of TWEAK and its receptor positively correlated to each other in SE lesions, but inversely correlated in AE lesions. These results shed light on potential pathogenic roles of these TNF factors in AE and SE, and pinpoint a potential of tailored treatments towards these factors in AE and SE.
TNF 家族细胞因子 BAFF（肿瘤坏死因子家族中的 B 细胞激活因子）和 APRIL（增殖诱导配体）是 B 细胞发育和激活的关键生存因子。已证明针对 B 细胞的治疗方法可改善特应性皮炎（AE），这表明这些细胞因子参与了 AE 的发病机制。因此，我们分析了这些 TNF 细胞因子在 AE、脂溢性湿疹（SE）和健康对照（HC）中的表达。通过 ELISA 测定 BAFF、APRIL 和密切相关的 TNF 成员 TWEAK（TNF 样弱凋亡诱导剂）的血清/血浆浓度。通过定量 RT-PCR 和免疫荧光分析这些细胞因子及其受体在皮肤中的表达。与其他炎症性疾病（包括自身免疫性疾病和哮喘）不同，AE 或 SE 患者的循环 BAFF、APRIL 和 TWEAK 水平与 HC 相比并未升高，也与 AE 患者的疾病严重程度或全身性 IgE 水平无关。有趣的是，我们发现，在 AE 患者的阳性变应原斑贴试验反应（APT-AE）和 AE 和 SE 患者的皮损中，这些细胞因子及其受体的表达发生了改变。AE 和 SE 的湿疹皮肤中 APRIL 的表达降低，BAFF 的表达增加，这可能导致对 B 细胞的负调节输入减少。在 APT-AE 中更为明显，APT-AE 是 AE 的起始急性阶段，这可能导致过度激活的 B 细胞失调。此外，SE 病变中 TWEAK 的表达水平与其受体呈正相关，而在 AE 病变中则呈负相关。这些结果揭示了这些 TNF 因子在 AE 和 SE 中的潜在致病作用，并指出针对这些因子进行 AE 和 SE 个体化治疗的潜力。
