Development of autoantibodies before the clinical onset of systemic lupus erythematosus
Development of autoantibodies before the clinical onset of systemic lupus erythematosus
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DOI：
10.1056/nejmoa021933
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发表时间：
2003-10-16
影响因子：
158.5
通讯作者：
Harley, JB
中科院分区：
文献类型：
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作者：
Arbuckle, MR;McClain, MT;Harley, JB
背景：尽管对全身性红斑狼疮（SLE）的自然史了解了很多知识，但尚未广泛探索疾病诊断之前的SLE自身抗体的发展。我们调查了临床诊断之前自动抗体开发的发作和进展。我们评估了从130人获得SLE诊断之前从130人获得的血清样品以及来自匹配的对照的样本。分子：在130名SLE患者中，有115例（88％）（88％）（至少有一个SLE自动抗体）在诊断之前就存在（最多9。4年；抗核抗体存在78％（稀释1：120或更多），抗双链DNA抗体的55％，抗RO抗体为47％，抗LA抗体为34％，抗SM抗体，抗SM抗体在32％中，抗核核糖核蛋白抗体为26％，抗磷脂抗体为18％。抗核，抗磷脂抗体，抗RO和抗LA抗体的存在早于抗SM和抗核核糖核蛋白抗体（诊断前3.4年，vs. 1.2年，p = 0.005）。在诊断前2。2年的平均发作的抗双链DNA抗体比抗核抗体（p = 0.06）晚2.2年，并且比抗核核糖核蛋白抗体（P = 0.005）早（p = 0.06）。对于许多患者，最早可用的血清样品为阳性。因此，从第一次阳性抗体测试到诊断的平均时间的这些度量是低估了从抗体发展到诊断的时间。在130个初始匹配的控件中，有3.8％的自身抗体是阳性的。判断：自身抗体通常在诊断SLE诊断之前多年。此外，SLE患者的自身抗体的出现往往遵循可预测的过程，在SLE发作之前，特定自身抗体的积累逐渐积累，而患者仍然无症状。
BACKGROUND:Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis.METHODS:The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls.RESULTS:In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti-double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 percent, anti-nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti-nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti-double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti-nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies.CONCLUSIONS:Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.