Wenzel Joerg, Lucas Svenja, Zahn Sabine, Mikus Sandra, Metze Dieter, Ständer Sonja, von Stebut Esther, Hillen Uwe, Bieber Thomas, Tüting Thomas
Department of Dermatology at the Universitie of Bonn, Bonn, Germany.
J Am Acad Dermatol. 2008 Mar;58(3):437-42. doi: 10.1016/j.jaad.2007.10.647.
Lichenoid graft-versus-host disease (liGVHD) histologically shares several common features with other lichenoid dermatoses, such as cutaneous lupus erythematosus and lichen planus (LP), which collectively show a junctional infiltrate of cytotoxic lymphocytes with liquefaction of the basal layer ("interface dermatitis"). Because recent studies have shown a role for type I interferon (IFN)-associated inflammation, including lymphocyte recruitment via CXCR3 <-> ligand interaction in cutaneous lupus erythematosus and LP, we hypothesized that similar mechanisms might also be involved in liGVHD.
Ten representative lesional skin biopsies taken from patients with different subsets of chronic cutaneous graft versus host disease (GvDH) were recovered from the authors' archives. Eight LP specimens and 5 punch biopsies taken from healthy skin were analyzed for control purposes. Immunohistochemistry was performed to characterize the lesional infiltrate (CD3, CD4, CD8, CD20, CD56, or CD68), to analyze type I IFN signaling (MxA), and to investigate expression of the IFN-inducible chemokines CXCL9 and CXCL10 and their ligand CXCR3. In situ hybridization was performed to visualize IFNalpha expression on the mRNA level.
Our analyses revealed striking similarities between the inflammatory pattern seen in LP and liGVHD. Both disorders presented with a predominantly T-cellular inflammation with CD8(+) lymphocytes affecting the basal epidermal layer. The majority of lesional lymphocytes expressed the chemokine receptor CXCR3. The corresponding chemokines CXCL9 and CXCL10 were found in the epidermis and within the inflammatory infiltrate. Analyses of MxA and IFNalpha mRNA expression supported a role for type I IFNs in these conditions.
This study was limited by the number of well characterized cases in our archives. In situ hybridization was realizable only in single cases.
Our results support the hypothesis that CXCR3 <-> ligand-mediated lymphocyte recruitment is involved in cutaneous liGVHD. The fact that CXCL10 was seen in precisely those areas with extensive liquefaction of the basal epidermis supports a role of this chemokine for the development of the typical histologic "interface" pattern.
苔藓样移植物抗宿主病（liGVHD）在组织学上与其他苔藓样皮肤病有一些共同特征，如皮肤红斑狼疮和扁平苔藓（LP），它们共同表现为细胞毒性淋巴细胞的界面浸润伴基底层液化（“界面性皮炎”）。由于最近的研究表明I型干扰素（IFN）相关炎症发挥作用，包括在皮肤红斑狼疮和LP中通过CXCR3 <->配体相互作用募集淋巴细胞，我们推测类似机制可能也参与liGVHD。
从作者的存档中获取10例取自不同亚型慢性皮肤移植物抗宿主病（GvDH）患者的代表性皮损活检标本。为作对照分析了8例LP标本和5例取自健康皮肤的打孔活检标本。进行免疫组织化学以鉴定皮损浸润（CD3、CD4、CD8、CD20、CD56或CD68），分析I型IFN信号传导（Mx A），并研究IFN诱导趋化因子CXCL9和CXCL10及其配体CXCR3的表达。进行原位杂交以在mRNA水平可视化IFNα表达。
我们的分析揭示了LP和liGVHD中炎症模式的显著相似性。两种疾病均主要表现为T细胞炎症，CD8(+)淋巴细胞累及基底表皮层。大多数皮损淋巴细胞表达趋化因子受体CXCR3。在表皮和炎症浸润中发现了相应的趋化因子CXCL9和CXCL10。Mx A和IFNα mRNA表达分析支持I型IFN在这些疾病中的作用。
本研究受限于我们存档中特征明确病例的数量。原位杂交仅在个别病例中可行。
我们的结果支持以下假设，即CXCR3 <->配体介导的淋巴细胞募集参与皮肤liGVHD。在基底表皮广泛液化的区域中确切观察到CXCL10这一事实支持了该趋化因子在典型组织学“界面”模式形成中的作用。
