Division of Endocrinology, Diabetes, & Metabolism, Rutgers New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey.
Immunology Section, Department of Medicine and The Webb-Waring Center, The University of Colorado Anschutz Medical Center, Aurora, Colorado.
J Clin Endocrinol Metab. 2018 Aug 1;103(8):2838-2842. doi: 10.1210/jc.2018-00568.
Immunotherapy trials to prevent type 1 diabetes have been unsuccessful for >15 years. Understanding pitfalls and knowledge gaps in the immunology of type 1 diabetes should lead us in new directions that will yield better trial outcomes. A proposal is made for precision medicine trial design in future type 1 diabetes studies.
High-quality peer-reviewed basic science and clinical research trials for type 1 diabetes were used in this Perspective article. Type 1 diabetes publications were reviewed from 2000 to 2018 by using Google Scholar and PubMed reference databases.
Personalized medicine for type 1 diabetes should recognize that each individual has phenotypic and genotypic quirks that distinguish them from other study participants. A uniform protocol for antigen-specific immunotherapy has consistently failed to prevent disease. An alternative approach using molecular tools to personalize the preventive treatment strategy might be a road forward for type 1 diabetes research. Assumptions or lack of knowledge about disease stratification (not all type 1 diabetes is the same disease), individualized antigen-specific T cells, regulatory T-cell populations, and T-cell receptor rearrangement are just a few aspects of immunology that require integration with clinical trial design.
The type 1 diabetes research community continues to bring forward novel immunotherapy trials to prevent disease, but this approach is unlikely to succeed until several fundamental aspects of clinical immunology are recognized and addressed. Here, we identify several knowledge gaps that could rectify type 1 diabetes trial design and lead to future success.
预防 1 型糖尿病的免疫疗法试验已经失败超过 15 年。了解 1 型糖尿病免疫学中的陷阱和知识空白，应能引导我们走向新的方向，从而产生更好的试验结果。本文提出了在未来 1 型糖尿病研究中进行精准医学试验设计的建议。
本文观点使用了高质量的同行评议基础科学和 1 型糖尿病临床研究试验。通过使用 Google Scholar 和 PubMed 参考数据库，对 2000 年至 2018 年的 1 型糖尿病出版物进行了回顾。
1 型糖尿病的个体化治疗应认识到，每个人都有表型和基因型的特点，使他们与其他研究参与者有所不同。针对特定抗原的免疫疗法的统一方案始终未能预防疾病。使用分子工具来个性化预防治疗策略的替代方法可能是 1 型糖尿病研究的一个前进方向。对疾病分层（并非所有 1 型糖尿病都是同一种疾病）、个体化抗原特异性 T 细胞、调节性 T 细胞群体和 T 细胞受体重排的假设或缺乏了解，只是免疫学中需要与临床试验设计相结合的几个方面。
1 型糖尿病研究界继续提出新的免疫疗法试验来预防疾病，但在认识和解决临床免疫学的几个基本方面之前，这种方法不太可能成功。在这里，我们确定了几个可能纠正 1 型糖尿病试验设计并带来未来成功的知识空白。
