Autoantibodies and Microvascular Damage Are Independent Predictive Factors for the Progression of Raynaud's Phenomenon to Systemic Sclerosis A Twenty-Year Prospective Study of 586 Patients, With Validation of Proposed Criteria for Early Systemic Sclerosis
Autoantibodies and Microvascular Damage Are Independent Predictive Factors for the Progression of Raynaud's Phenomenon to Systemic Sclerosis A Twenty-Year Prospective Study of 586 Patients, With Validation of Proposed Criteria for Early Systemic Sclerosis
复制标题
DOI：
10.1002/art.24038
复制
发表时间：
2008-12-01
影响因子：
--
通讯作者：
Senecal, Jean-Luc
中科院分区：
文献类型：
--
作者：
Koenig, Martial;Joyal, France;Senecal, Jean-Luc
目标。目的：鉴别雷诺现象（RP）患者中预测发展为明确系统性硬化症（SSc）的独立标志物，确定进展为SSc患者微血管损伤的类型和顺序及其与SSc特异性自身抗体的关系。没有明确结缔组织疾病的连续患者接受R-P评估，通过甲折毛细血管显微镜（NCM）评估微血管损伤，并通过特异性测定评估抗着丝粒（抗cenp - b）、抗th /To、抗拓扑异构酶1和抗rna聚合酶III（抗rnap III）自身抗体。对患者进行前瞻性研究。在随访3197人年的586例患者中，74例（12.6%）发展为明确的SSc。微血管损伤的特征性序列被确定，从毛细血管扩张开始，接着是毛细血管损失，然后是毛细血管扩张。明确的SSc诊断与毛细血管损失在时间上密切相关。毛细血管增大、毛细血管损失和SSc特异性自身抗体独立预测SSc的确定。抗cenp - b和抗th /To抗体预测毛细血管扩张；这些自身抗体和抗rnap III预测毛细血管损失。每种自身抗体与微血管损伤的不同时间过程相关。在随访中，79.5%的这些自身抗体为1且基线时NCM检查异常的患者发展为明确的SSc。具有这两种基线预测指标的患者发展为明确SSc的可能性高出60倍。这些数据验证了早期ssc的诊断标准。在RP发展为明确的SSc时，微血管损伤是动态和连续的，而SSc特异性自身抗体与毛细血管异常的过程和类型相关。基线时NCM的异常发现以及SSc特异性自身抗体表明发展为明确的SSc的可能性非常高，而它们的缺失则排除了这一结果。
Objective. To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies.Methods. Consecutive patients referred for evaluation of R-P who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti-CENP-B), anti-Th/To, anti-topoisomerase 1, and anti-RNA polymerase III (anti-RNAP III) auto-antibodies by specific assays. Patients were studied prospectively.Results. Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti-CENP-B and antiTh/To antibodies predicted enlarged capillaries; these autoantibodies and anti-RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with I of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc.Conclusion. In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.