Department of Oncology, Transplants and Advanced Technologies in Medicine, Division of Paleopathology, History of Medicine and Bioethics, University of Pisa, Italy.
Clin Exp Rheumatol. 2012 Jan-Feb;30(1):12-22. Epub 2012 Mar 6.
The paleopathological study of the skeletal remains belonging to Cardinal Carlo de' Medici (1595-1666), son of Ferdinando I (1549-1609) and Cristina of Lorena (1565-1637), has been presented previously. A diagnosis of Klippel-Feil syndrome, tuberculosis and a polyarthopathy, interpreted as rheumatoid arthritis, was suggested. A revision of this case based on the analysis of the historical documents and of some radiological images of Carlo's bones has been proposed recently; according to the Authors, the Cardinal was affected by the 'Medici syndrome', a combined Psoriatic-DISH arthropathy. This revision offers us the opportunity to discuss this complex case, comparing different points of view, and to present the results of the molecular analyses carried out on Carlo's bone samples. We looked for the genetic risk factors of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We also searched for the primary candidate genes of RA and PsA, i.e. DR4 or DR1 and Cw6 or DR7 respectively, the latter predisposing also for psoriasis.
An original molecular protocol was applied to achieve an aDNA uncontaminated by exogenous sources and almost intact, starting from one of the Cardinal's rib pieces. The allele risk factors for both diseases were identified by PCR-SSP assay as HLA genotyping methodology.
Our data assigned Carlo the genotype DRB1*04/11 for HLA-DRB locus and Cw04/*12 for HLA-C locus.
Since Carlo was infected by M. tuberculosis during infancy and was carrying the DR4 variant but not the Cw6, he surely had a predisposition to RA, not to PsA and/or psoriasis. The diagnosis of RA is thus confirmed.
此前曾对红衣主教卡洛·德·美第奇（1595-1666 年）的骨骼遗骸进行了古病理学研究，他是费迪南多一世（1549-1609 年）和克里斯蒂娜·德·洛林（1565-1637 年）的儿子。提出的诊断为克莱佩尔-费尔综合征、结核病和多关节炎，解释为类风湿关节炎。最近根据卡洛骨骼的历史文献和一些影像学图像的分析，对该病例进行了修订；根据作者的说法，红衣主教患有“美第奇综合征”，即一种联合的银屑病-DISH 关节病。这次修订为我们提供了一个机会，通过比较不同的观点来讨论这个复杂的病例，并介绍对卡洛骨骼样本进行的分子分析结果。我们寻找了类风湿关节炎（RA）和银屑病关节炎（PsA）的遗传风险因素。我们还搜索了 RA 和 PsA 的主要候选基因，即 DR4 或 DR1 和 Cw6 或 DR7，后者也容易引发银屑病。
应用原始的分子方案，从红衣主教的一根肋骨中获得不受外源污染且几乎完整的 aDNA。通过 PCR-SSP 测定法作为 HLA 基因分型方法，鉴定两种疾病的等位基因风险因素。
我们的数据将卡洛的 HLA-DRB 基因座基因型分配为 DRB1*04/11，HLA-C 基因座基因型为 Cw04/*12。
由于卡洛在婴儿期感染了结核分枝杆菌，并且携带 DR4 变体但不携带 Cw6，他肯定有患 RA 的倾向，而不是 PsA 和/或银屑病。因此，RA 的诊断得到了确认。
