Caproni Marzia, Giomi Barbara, Volpi Walter, Melani Lucilla, Schincaglia Emiliano, Macchia Donatella, Manfredi Mariangela, D'Agata Alberino, Fabbri Paolo
II Department of Dermatological Sciences, University of Florence, Via degli Alfani, 37, 50121 Florence Italy.
Clin Immunol. 2005 Mar;114(3):284-92. doi: 10.1016/j.clim.2004.10.007.
The term chronic autoimmune urticaria (CAIU) is used for chronic urticaria in subjects who present a whealing response to the intradermal injection of autologous serum, suggesting the presence of pathogenic antibody activities. In this study, we examined 28 chronic urticaria subjects with positive autologous serum skin test (ASST), all of whom presented autologous serum-induced lesions at different evolutive stages. Punch biopsies were taken from lesional skin of six subjects at 10', eight subjects at 30', six subjects at 60', and four subjects each at 24 and 48 h. Immunological studies focussed on infiltrating cell immunophenotype and related cytokines, chemokines and chemokine receptors, adhesion molecules. Immunohistochemical staining was performed to measure expression of CD3, CD4, CD8, tryptase, eosinophil cationic protein, myeloperoxidase, basophil granular protein, IL-4, IL-5, IL-8, CCR3 and CXCR3, ICAM-1, VCAM and ELAM. Control staining was done on unaffected skin from the patients and normal skin from four healthy donors. The main infiltrating population was represented by neutrophils, seen focally in both unaffected skin (P = 0.001) and healthy controls (P = 0.003). IFN-gamma and IL-5 were expressed focally in autologous wheals. Significant staining for IL-4 was seen at 30'. CCR3 and CXCR3 were expressed less in autologous wheals than in uninvolved skin (P < 0.0001; P = 0.002). Cellular adhesion molecules (CAMs) reached their highest expression at 30' and 60' in induced lesions, and they showed strong expression also in unaffected skin (ICAM-1: P < 0.0001). Our data show that the immunoinflammatory features of ASST-induced wheals involve a prevalent role of lymphocytes (with a mixed Th1/Th2 response), with strong neutrophil infiltration and activity and involvement of the chemokine pathway. We interpreted the finding of inflammatory cells and mediator up-regulation in uninvolved CIU skin as a sign of prolonged and widespread "urticarial status".
慢性自身免疫性荨麻疹（CAIU）这一术语用于描述那些对皮内注射自体血清出现风团反应的慢性荨麻疹患者，提示存在致病性抗体活性。在本研究中，我们检查了28例自体血清皮肤试验（ASST）呈阳性的慢性荨麻疹患者，所有患者在不同演变阶段均出现了自体血清诱导的皮损。分别在10分钟时从6例患者的皮损处、30分钟时从8例患者的皮损处、60分钟时从6例患者的皮损处以及24小时和48小时时从4例患者的皮损处取打孔活检组织。免疫学研究聚焦于浸润细胞免疫表型以及相关的细胞因子、趋化因子和趋化因子受体、黏附分子。进行免疫组织化学染色以检测CD3、CD4、CD8、类胰蛋白酶、嗜酸性粒细胞阳离子蛋白、髓过氧化物酶、嗜碱性粒细胞颗粒蛋白、IL-4、IL-5、IL-8、CCR3和CXCR3、ICAM-1、VCAM和ELAM的表达。对患者未受累皮肤以及4名健康供者的正常皮肤进行对照染色。主要浸润细胞群体为中性粒细胞，在未受累皮肤（P = 0.001）和健康对照中（P = 0.003）均可见局灶性分布。IFN-γ和IL-5在自体风团中呈局灶性表达。在30分钟时可见IL-4有明显染色。CCR3和CXCR3在自体风团中的表达低于未受累皮肤（P < 0.0001；P = 0.002）。细胞黏附分子（CAMs）在诱导皮损的30分钟和60分钟时表达达到最高，且在未受累皮肤中也有强表达（ICAM-1：P < 0.0001）。我们的数据表明，ASST诱导的风团的免疫炎症特征涉及淋巴细胞的普遍作用（伴有混合的Th1/Th2反应），伴有强烈的中性粒细胞浸润和活性以及趋化因子途径的参与。我们将在未受累的慢性荨麻疹皮肤中发现炎症细胞和介质上调解释为长期广泛的“荨麻疹状态”的标志。
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