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    • Decreased Plasma Level of Cytokeratin 20 (KRT20) is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement

    Nikolett Lupsa,Akos Szegedi,Andras Gezsi,Zoltan Vuncs,Tamas Masszi,Gabor Mikala,Peter Remenyi,Sara Deola,Arun Prasath Lakshmanan,Annalisa Terranegra,Edit Buzas,Zoltan Pos

    Biomedicines（2022）

    Semmelweis Univ | Budapest Univ Technol & Econ | South Pest Ctr Hosp | Sidra Med

    Cited 1|Views21
    Abstract
    Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two established markers of skin- and gut aGvHD. The discovery cohort (n = 39) revealed that at the time of diagnosis, plasma KRT20 showed a progressive decrease from unaffected individuals to patients with single-, and patients with multi-organ aGvHD. KRT20 was affected by cutaneous (p = 0.0263) and gastrointestinal aGvHD (p = 0.0242) independently and in an additive manner. Sensitivity and specificity of KRT20 for aGvHD involving both target organs (AUC = 0.852) were comparable to that of PI3 for skin-aGvHD (AUC = 0.708) or that of REG3A for gut-aGvHD (AUC = 0.855). Patient follow-up in the validation cohort (n = 67) corroborated these observations (p < 0.001), and linked low KRT20 to grade 2+ disease (p < 0.001), but failed to confirm low KRT20 as an independent risk factor. These data established a link between low plasma KRT20 levels and moderate to severe aGvHD involving multiple target organs.
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    Key words
    acute graft versus host disease,aGvHD,biomarker,cytokeratin 20,KRT20,K20
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    【要点】：该论文探讨了三种主要在皮肤和肠道表达的浆蛋白——细胞角蛋白15（KRT15）、细胞角蛋白20（KRT20）和闭塞蛋白（OCLN），在急性移植物抗宿主病（aGvHD）发病及严重程度中的作用，发现KRT20的浆水平降低与aGvHD的出现及其严重程度相关，且不受器官受累类型的影响。
    

    【方法】：研究者通过酶联免疫吸附试验（ELISA）对包含发现队列（n=39）和验证队列（n=67）的患者的血浆蛋白水平进行了评估，并与已知的皮肤和肠道aGvHD标记物弹性纤维素（PI3）和再生家族成员3α（REG3A）进行了比较。
    

    【实验】：在发现队列中，诊断时，从未受影响个体到单个器官受累的患者，再到多器官受累的患者，血浆KRT20水平呈进行性降低。KRT20受皮肤（p=0.0263）和肠道aGvHD（p=0.0242）影响，且是独立和叠加的方式。涉及两个目标器官的aGvHD的KRT20的敏感性和特性与皮肤aGvHD的PI3（AUC=0.708）或肠道aGvHD的REG3A（AUC=0.855）相当。在验证队列中，患者的随访证实了这些发现（p<0.001），并发现低KRT20与II级及以上疾病（p<0.001）相关，但未证实低KRT20是一个独立的危险因素。这些数据确立了低血浆KRT20水平与涉及多个目标器官的中到重度aGvHD之间的联系。