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非速发型皮肤过敏性药物反应患者外周血淋巴细胞中皮肤归巢受体的表达。

Expression of the skin-homing receptor in peripheral blood lymphocytes from subjects with nonimmediate cutaneous allergic drug reactions.

作者信息

Blanca M, Posadas S, Torres M J, Leyva L, Mayorga C, Gonzalez L, Juarez C, Fernández J, Santamaria L F

机构信息

Allergy Service, La Paz Hospital, Madrid, Spain.

出版信息

Allergy. 2000 Nov;55(11):998-1004. doi: 10.1034/j.1398-9995.2000.00628.x.

Abstract

BACKGROUND

In nonimmediate cutaneous reactions to drugs, the skin is the organ most frequently involved, and T cells may play a relevant role. T cells related to skin immune responses express the cutaneous lymphocyte-associated antigen (CLA), the skin-homing receptor.

METHODS

We studied the expression of the CLA in peripheral blood T cells from nine subjects with exanthematous reactions induced by beta-lactams (4), phenytoin (2), propyphenazone (1), spiramycin plus metronidazol (1), and captopril plus tiazide (1). The cutaneous symptoms appeared at least 6 h after drug intake. CLA expression was evaluated by flow cytometry at the time of the reaction (T1) and 1 month later (T2). HLA-DR activation marker expression was also evaluated at T1. In four patients, it was necessary to readminister the culprit drug to establish a causal relationship, and sequential estimation of the markers was performed. Two control groups were included: healthy controls and subjects exposed to the culprit drugs with good tolerance. Values were compared by nonparametric statistics.

RESULTS

The expression of circulating CLA + T cells at T1 was increased compared to healthy controls (median = 20.4 vs 9.4) (P < 0.001), and the patients also expressed increased levels of HLA-DR (median = 3.8) (P < 0.005). Comparison between T1 and T2 (median = 11.2) also showed differences in levels of CLA+ T cells (P < 0.01). The patients re-exposed to the culprit drug showed an increase followed by a decrease of circulating CLA+ T cells (P < 0.05) and CLA+ HLA-DR+ (P < 0.05) paralleling the symptoms.

CONCLUSIONS

These data support the immunologic nature of delayed skin reactions to drugs, and suggest that these CLA+ T cells parallel the disease evolution and may participate in the pathophysiologic mechanisms.

摘要

背景

在药物的非即刻皮肤反应中,皮肤是最常受累的器官,T细胞可能发挥相关作用。与皮肤免疫反应相关的T细胞表达皮肤淋巴细胞相关抗原(CLA),即皮肤归巢受体。

方法

我们研究了9名出现皮疹反应患者外周血T细胞中CLA的表达情况,这些反应由β-内酰胺类药物(4例)、苯妥英(2例)、保泰松(1例)、螺旋霉素加甲硝唑(1例)以及卡托普利加噻嗪类利尿剂(1例)诱发。皮肤症状在服药后至少6小时出现。在反应发生时(T1)和1个月后(T2)通过流式细胞术评估CLA表达。在T1时还评估了HLA-DR激活标志物的表达。在4例患者中,有必要重新给予致病药物以确定因果关系,并对标志物进行连续评估。纳入了两个对照组:健康对照者和对致病药物耐受性良好的受试者。通过非参数统计比较数值。

结果

与健康对照者相比,T1时循环CLA + T细胞的表达增加(中位数分别为20.4对9.4)(P < 0.001),患者的HLA-DR水平也升高(中位数为3.8)(P < 0.005)。T1和T2(中位数为11.2)之间的比较也显示CLA + T细胞水平存在差异(P < 0.01)。再次接触致病药物的患者循环CLA + T细胞先增加后减少(P < 0.05),CLA + HLA-DR + 也如此(P < 0.05),与症状平行。

结论

这些数据支持药物延迟皮肤反应的免疫性质,并表明这些CLA + T细胞与疾病进展平行,可能参与病理生理机制。

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