Plasma of patients with chronic urticaria shows signs of thrombin generation, and its intradermal injection causes wheal-and-flare reactions much more frequently than autologous serum
Plasma of patients with chronic urticaria shows signs of thrombin generation, and its intradermal injection causes wheal-and-flare reactions much more frequently than autologous serum
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DOI：
10.1016/j.jaci.2005.12.1343
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发表时间：
2006-05-01
影响因子：
14.2
通讯作者：
Cugno, M
中科院分区：
文献类型：
--
作者：
Asero, R;Tedeschi, A;Cugno, M
背景：慢性荨麻疹（CU）发病机制的几个方面仍然是矛盾的。自体血清皮肤试验（ASST）和体外组胺释放试验似乎可以研究该疾病的不同方面，但 ASST 的特异性受到质疑。目的：我们将自体血浆皮肤试验 (APST) 与 ASST 进行比较，以检测 CU 患者的自身反应性。还通过测量体内凝血酶生成来研究凝血过程。方法：总共 96 名患有 CU 的成人接受了 ASST；其中 71 人接受了柠檬酸钠抗凝血浆的 APST。通过夹心 ELISA 测量 28 名患者和 27 名对照者的柠檬酸钠抗凝血浆中的凝血酶原片段 1+2 血浆水平。结果：96 名患者中的 51 名 (53%) 患者 ASST 评分呈阳性，而 71 名患者中 61 名 (86%) 患者 APST 评分阳性（21/30 [70%] ASST 阴性，40/41 [98%] ASST 阳性）。患者血浆凝血酶原片段 1+2 高于对照组（3.06 [SD 3.36] vs 0.80 [0.34]；P < .001），ASST 阳性/APST 阳性患者高于 ASST 阴性/APST 阳性患者（3.89 [SD 3.68] vs 1.33 [1.64]；P = 0.058），并且与荨麻疹严重程度（r = 0.37; P < .05)。结论：大多数 CU 患者 APST-柠檬酸钠呈阳性。 CU 与凝血酶的产生有关，凝血酶是一种丝氨酸蛋白酶，能够激活肥大细胞并导致内皮细胞通透性相应增加。 APST 和 ASST 仅部分依赖于 Fc epsilon RI 或 IgE 循环抗体的存在。临床意义：这些发现为 CU 的发病机制提供了新的见解，并提出了治疗该疾病的新的治疗机会。
Background: Several aspects of the pathogenesis of chronic urticaria (CU) remain contradictory. Autologous serum skin tests (ASSTs) and in vitro histamine release assays seem to look into distinct aspects of the disease, and the specificity of ASST has been questioned. Objective: We compared the autologous plasma skin test (APST) with ASST to detect autoreactivity in patients with CU. The clotting process was investigated as well by measuring in vivo thrombin generation.Methods: A total of 96 adults with CU underwent ASST; 71 of them underwent APST with Na citrate-anticoagulated plasma. Prothrombin fragment 1+2 plasma levels were measured by a sandwich ELISA in Na citrate-anticoagulated plasmas from 28 patients and 27 controls.Results: Fifty-one of 96 (53%) patients scored positive on ASST, whereas 61 of 71 (86%) patients scored positive on APST (21/30 [70%] ASST-negative and 40/41 [98%] ASST-positive). Plasma prothrombin fragment 1+2 was higher in patients than controls (3.06 [SD 3.36] vs 0.80 [0.34]; P < .001) and in ASST-positive/APST-positive than in ASST-negative/APST-positive patients (3.89 [SD 3.68] vs 1.33 [1.64]; P = 0.058) and was directly related to urticaria severity (r = 0.37; P < .05).Conclusion: Most patients with CU are positive on APST-Na citrate. CU is associated with the generation of thrombin, a serine protease able to activate mast cells and to cause relevant increase in permeability of endothelium. APST and ASST only partially depend on the presence of circulating antibodies to Fc epsilon RI or to IgE.Clinical implications: These findings provide new insights into the pathogenesis of CU and suggest new therapeutic opportunities far treating this disease.