Johnston Stephen Albert, Thamm Douglas H, Legutki Joseph Barten
Center for Innovations in Medicine, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-5901, USA.
BMC Cancer. 2014 Sep 8;14:657. doi: 10.1186/1471-2407-14-657.
Cancer diagnosis in both dogs and humans is complicated by the lack of a non-invasive diagnostic test. To meet this clinical need, we apply the recently developed immunosignature assay to spontaneous canine lymphoma as clinical proof-of-concept. Here we evaluate the immunosignature as a diagnostic for spontaneous canine lymphoma at both at initial diagnosis and evaluating the disease free interval following treatment.
Sera from dogs with confirmed lymphoma (B cell n = 38, T cell n = 11) and clinically normal dogs (n = 39) were analyzed. Serum antibody responses were characterized by analyzing the binding pattern, or immunosignature, of serum antibodies on a non-natural sequence peptide microarray. Peptides were selected and tested for the ability to distinguish healthy dogs from those with lymphoma and to distinguish lymphoma subtypes based on immunophenotype. The immunosignature of dogs with lymphoma were evaluated for individual signatures. Changes in the immunosignatures were evaluated following treatment and eventual relapse.
Despite being a clonal disease, both an individual immunosignature and a generalized lymphoma immunosignature were observed in each dog. The general lymphoma immunosignature identified in the initial set of dogs (n = 32) was able to predict disease status in an independent set of dogs (n = 42, 97% accuracy). A separate immunosignature was able to distinguish the lymphoma based on immunophenotype (n = 25, 88% accuracy). The individual immunosignature was capable of confirming remission three months following diagnosis. Immunosignature at diagnosis was able to predict which dogs with B cell lymphoma would relapse in less than 120 days (n = 33, 97% accuracy).
We conclude that the immunosignature can serve as a multilevel diagnostic for canine, and potentially human, lymphoma.
犬类和人类的癌症诊断因缺乏非侵入性诊断测试而变得复杂。为满足这一临床需求，我们将最近开发的免疫印记分析应用于自发性犬淋巴瘤，作为临床概念验证。在此，我们评估免疫印记在犬淋巴瘤初始诊断及评估治疗后的无病间期时作为诊断方法的效果。
分析确诊为淋巴瘤的犬（B细胞型n = 38，T细胞型n = 11）和临床正常犬（n = 39）的血清。通过分析血清抗体在非天然序列肽微阵列上的结合模式（即免疫印记）来表征血清抗体反应。选择肽并测试其区分健康犬和淋巴瘤犬以及根据免疫表型区分淋巴瘤亚型的能力。评估淋巴瘤犬的免疫印记以确定个体特征。在治疗及最终复发后评估免疫印记的变化。
尽管淋巴瘤是一种克隆性疾病，但在每只犬中均观察到个体免疫印记和广义的淋巴瘤免疫印记。在最初一组犬（n = 32）中确定的广义淋巴瘤免疫印记能够在另一组独立犬（n = 42，准确率97%）中预测疾病状态。一种单独的免疫印记能够根据免疫表型区分淋巴瘤（n = 25，准确率88%）。个体免疫印记能够在诊断后三个月确认缓解状态。诊断时的免疫印记能够预测哪些B细胞淋巴瘤犬会在120天内复发（n = 33，准确率97%）。
我们得出结论，免疫印记可作为犬类乃至人类淋巴瘤的多级诊断方法。
