Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Unit of Rheumatology, Policlinico Le Scotte, University of Siena, Italy.
Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):1133-41. doi: 10.1177/039463201002300417.
To date, the rate of detection of autoinflammatory gene mutations in patients suspected of having an autoinflammatory disorder is very low. However, most of these data refer to pediatric populations. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that mutations will be found in an even smaller percentage of cases. Our aim was to develop and validate a set of variables for predicting the risk that a given adult patient presenting with recurrent fever episodes carries mutations in the MEFV or TNFRSF1A genes, in order to increase the probability of obtaining positive results on genetic testing. One hundred and ten consecutive patients with a clinical history of periodic fever attacks were screened for mutations in the TNFRSF1A and the MEFV genes. The mean age at disease onset was 27.85 years. Detailed information about each patient?s family history, personal history, and clinical manifestations were retrospectively collected. A diagnostic score was constructed based on univariate and multivariate analysis in a randomly-selected dataset (training set; n=40). The score was validated on an independent set of the remaining patients (validation set; n=70). Age at onset (odds ratio 0.958, P =0.050), positive family history of recurrent fever episodes (OR 5.738, P = 0.006 ), thoracic pain (OR 7.390, P = 0.002), abdominal pain (OR 2.853, P = 0.038) and skin involvement (OR 8.241, P = 0.003) were independently correlated with a positive genetic test result. A diagnostic score was calculated using the linear combination of the estimated coefficients of the logistic model (cut off equal to 0.24) revealing high sensitivity (0.94), high specificity (0.94) and high accuracy (0.94). We have identified variables that appear to be strongly related to the probability of detecting gene mutations in MEF and TNFRSF1A in adults, thus improving the evaluation of patients with suspected autoinflammatory disorders.
迄今为止，在疑似自身炎症性疾病患者中检测到自身炎症基因突变的比率非常低。然而，这些数据大多来自儿科人群。成人发病的自身炎症性疾病相对罕见，且信息有限，这使得在更小比例的病例中发现突变的可能性更大。我们的目的是开发和验证一组变量，用于预测具有复发性发热发作的特定成年患者携带 MEFV 或 TNFRSF1A 基因突变的风险，以提高遗传检测获得阳性结果的概率。我们对 110 例连续的周期性发热发作患者进行了 TNFRSF1A 和 MEFV 基因突变筛查。疾病发作的平均年龄为 27.85 岁。我们回顾性地收集了每位患者的家族史、个人史和临床表现的详细信息。在随机选择的数据集（训练集；n=40）中进行了单变量和多变量分析，构建了诊断评分。在剩余的患者（验证集；n=70）的独立数据集上验证了该评分。发病年龄（优势比 0.958，P=0.050）、反复发热家族史阳性（OR 5.738，P=0.006）、胸痛（OR 7.390，P=0.002）、腹痛（OR 2.853，P=0.038）和皮肤受累（OR 8.241，P=0.003）与阳性基因检测结果独立相关。使用逻辑模型的估计系数的线性组合计算诊断评分（截止值等于 0.24），显示出高敏感性（0.94）、高特异性（0.94）和高准确性（0.94）。我们已经确定了一些变量，这些变量似乎与成年患者中 MEF 和 TNFRSF1A 基因检测突变的概率密切相关，从而提高了对疑似自身炎症性疾病患者的评估。
