Department of Dermatology, Mayo Clinic, Rochester, MN, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Clin Exp Dermatol. 2019 Jun;44(4):e81-e88. doi: 10.1111/ced.13759. Epub 2018 Oct 2.
In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin.
To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens.
We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE.
Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0).
The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.
在急性移植物抗宿主病(GVHD)和红斑狼疮(LE)中,患者自身的组织通过受干扰素(IFN)和其他细胞因子影响的复杂机制受到免疫攻击。尽管这两种疾病在临床上通常不会混淆,但它们在皮肤的组织病理学表现上有重叠。
通过皮肤标本的分子方法评估 GVHD 是否可以与 LE 区分开来。
我们开发了一种基于已鉴定的皮肤 GVHD 组织生物标志物的定量逆转录 PCR 检测方法,并比较了 GVHD 和 LE 中的基因表达。
两种疾病均表现出 IFN 诱导基因以及参与抗原呈递、细胞信号转导和组织修复的基因的强烈表达。与 LE 相比,GVHD 中的基因表达水平差异显著,尤其是 IFN 诱导基因,如 MX1、OAS3、TAP1 和 STAT3(P<0.01)。三个逻辑回归模型可以非常确定地区分这两种疾病(ROC 曲线下面积为 1.0)。
该研究证明了使用基于组织的分子技术区分显微镜下相似的炎症性皮肤病的可行性。