Patients with Nucleophosmin (NPM)-Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) mount ALK autoantibodies. The titer of these autoantibodies inversely correlates with the risk of relapse.

The epitopes recognized by these autoantibodies in NPM-ALK might be associated with different ALK-antibody levels. We used overlapping peptide microarray technology to analyze epitope-binding to NPM-ALK by plasma or serum from 129 ALK-positive ALCL patients and 21 controls. Antibodies present in sera from ALCL patients bound to epitopes mainly in the C-terminal region of the ALK portion of NPM-ALK (amino acid positions 469–496, 561–588, 617–644). Patients with higher ALK antibody titers detected the epitope 561–588 more frequently as well as three further epitopes at the N-terminus of the kinase domain compared to patients with intermediate and low titers.

These results identify new potential target epitopes for immunotherapy in ALK-positive ALCL. The methodology can be adapted for more reproducible analyses of tumor antigen detection.

核蛋白（NPM）-间变性淋巴瘤激酶（ALK）阳性，间变性大细胞淋巴瘤（ALCL）的患者可安装ALK自身抗体。这些自身抗体的效价与复发风险成反比。

这些自身抗体在NPM-ALK中识别的表位可能与不同的ALK抗体水平有关。我们使用重叠肽微阵列技术分析了129名ALK阳性ALCL患者和21名对照的血浆或血清与NPM-ALK的表位结合。来自ALCL患者的血清中存在的抗体主要与抗原决定簇结合，这些抗原决定簇位于NPM-ALK的ALK部分的C末端区域（氨基酸位置469-496、561-588、617-644）。与滴度中等和滴度较低的患者相比，ALK抗体滴度较高的患者更频繁地检测到表位561–588，并且在激酶结构域N端还发现了另外三个表位。

这些结果确定了在ALK阳性ALCL中用于免疫治疗的新的潜在靶标表位。该方法可以适用于肿瘤抗原检测的更可重复的分析。