T 细胞与 BP180 的 NC16A 结构域反应，存在于阴部硬化性苔藓和扁平苔藓中。

T cells reactive with the NC16A domain of BP180 are present in vulval lichen sclerosus and lichen planus.

机构信息

Department of Dermatology, University of Oxford, Oxford, UK.

出版信息

J Eur Acad Dermatol Venereol. 2010 Feb;24(2):186-90. doi: 10.1111/j.1468-3083.2009.03375.x. Epub 2009 Aug 14.

DOI:10.1111/j.1468-3083.2009.03375.x

PMID:19686329

Abstract

BACKGROUND

Lichen sclerosus (LS) is a chronic inflammatory skin condition. The recent demonstration of circulating autoantibodies to extracellular matrix protein 1 and to basement membrane zone (BMZ) components, chiefly BP180, suggests that autoimmunity to these components might contribute to pathogenesis. However, there is no binding of autoantibodies in vivo and as LS is characterized by a lymphocytic infiltrate, it seems likely that LS is mediated, in part, by antigen-specific lymphocytes. Similar mechanisms may apply to vulval lichen planus (LP), an interface dermatitis, with clinical and immunological overlap with LS.

OBJECTIVES

This study aims to test the hypothesis that T cells reactive with the NC16A domain of BP180 are present in the peripheral blood of patients with vulval LS and LP.

METHODS

Isolated peripheral blood mononuclear cells from 14 patients with vulval LS, 5 with vulval LP and 4 healthy controls were grown in vitro. We examined for immunogenicity of overlapping peptides spanning the NC16A domain of BP180 using interferon-gamma enzyme-linked immunospot assay (ELIspot) on the cultured T-cell lines. BMZ antibodies were assayed, HLA type determined and clinical parameters noted.

RESULTS

Significant interferon-gamma production was observed in response to the NC16A peptides in 6 of the 14 vulval LS and 2 of the 5 LP patients, but not in the control subjects. There was an associated autoantibody response to BP180 in 3 LS and 1 LP patient with T-cell responses. These data suggest that in some vulval LS and LP patients, NC16A domain-specific T cells circulate at sufficiently high frequency to be detectable in vitro and show rapid effector function. There was no association with HLA type or clinical parameters.

CONCLUSION

We have demonstrated that in > 40% of our vulval LS and LP patients, the NC16A domain of BP180 is a target for circulating T cells, and in vulval LS and LP there are associated autoantibodies to BP180.

摘要

背景

硬化性苔藓（LS）是一种慢性炎症性皮肤病。最近发现，细胞外基质蛋白 1 和基底膜带（BMZ）成分的循环自身抗体，主要是 BP180，表明这些成分的自身免疫可能有助于发病机制。然而，体内没有自身抗体的结合，并且由于 LS 的特征是淋巴细胞浸润，因此 LS 似乎部分由抗原特异性淋巴细胞介导。类似的机制可能适用于外阴扁平苔藓（LP），这是一种界面性皮炎，与 LS 具有临床和免疫学重叠。

目的

本研究旨在检验假设，即 BP180 的 NC16A 结构域反应性 T 细胞存在于外阴 LS 和 LP 患者的外周血中。

方法

从 14 例外阴 LS、5 例外阴 LP 和 4 例健康对照者的外周血单核细胞中分离出来，在体外培养。我们使用干扰素-γ酶联免疫斑点（ELIspot）检测 BP180 的 NC16A 结构域重叠肽的免疫原性，以检测培养的 T 细胞系。检测 BMZ 抗体，确定 HLA 类型并记录临床参数。

结果

在 14 例外阴 LS 患者和 5 例 LP 患者中，有 6 例和 2 例对 NC16A 肽产生明显的干扰素-γ产生，但对照组没有。在 3 例 LS 和 1 例 LP 患者中，存在与 T 细胞反应相关的 BP180 自身抗体反应。这些数据表明，在一些外阴 LS 和 LP 患者中，NC16A 结构域特异性 T 细胞以足够高的频率循环，可在体外检测到，并显示出快速的效应功能。与 HLA 类型或临床参数无关。