Petri Michelle, Stohl William, Chatham Winn, McCune W Joseph, Chevrier Marc, Ryel Jeff, Recta Virginia, Zhong John, Freimuth William
Johns Hopkins University School of Medicine, Division of Rheumatology, Baltimore, MD 21205, USA.
Arthritis Rheum. 2008 Aug;58(8):2453-9. doi: 10.1002/art.23678.
To determine the association of plasma B lymphocyte stimulator (BLyS) levels, immunosuppressive therapy, and other clinical parameters with disease activity in systemic lupus erythematosus (SLE).
Two hundred forty-five SLE patients were evaluated prospectively over a 2-year period at 4 centers. Assessments were performed every 3-6 months. Univariate analysis was used to determine the association among the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, serum anti-double-stranded DNA (anti-dsDNA), and plasma BLyS levels. A multivariate repeated-measures model incorporating immunosuppressive therapy was utilized.
Ninety-two percent of the patients were female. Sixty-seven percent were white, 31% African American, and 2% Asian (all of these groups may include Hispanic). Mean values at baseline were as follows: age 41.5 years, disease duration 8.1 years, SELENA-SLEDAI 3.3 (median 2, range 0-18), BLyS 5.57 ng/ml, IgG 1,439 mg/dl, C3 104.4 mg/dl, and C4 21.3 mg/dl; among those positive for anti-dsDNA, the median titer was 1:40 (range 1:10-1:1,280). Univariate analysis showed that plasma BLyS levels were associated with anti-dsDNA titers (P = 0.0465) and SELENA-SLEDAI scores (P = 0.0002). In multivariate analyses, a greater increase in the SELENA-SLEDAI score from the previous visit was associated with higher BLyS levels at the previous visit (P = 0.0042) and with a greater increase in the BLyS level from the previous visit (P = 0.0007).
The findings of association between a greater increase in the BLyS level from the previous visit and a greater increase in the SELENA-SLEDAI score at the subsequent visit, and between an elevated BLyS level at the previous visit and a greater SELENA-SLEDAI score at the subsequent visit, demonstrate a relationship between circulating BLyS levels and SLE disease activity. These results lend support to the notion that BLyS is a candidate for therapeutic targeting in SLE.
确定血浆B淋巴细胞刺激因子（BLyS）水平、免疫抑制治疗及其他临床参数与系统性红斑狼疮（SLE）疾病活动度之间的关联。
在4个中心对245例SLE患者进行了为期2年的前瞻性评估。每3 - 6个月进行一次评估。采用单因素分析确定系统性红斑狼疮疾病活动指数（SLEDAI）的狼疮性红斑中雌激素安全性全国评估（SELENA）版本评分、血清抗双链DNA（抗dsDNA）和血浆BLyS水平之间的关联。使用纳入免疫抑制治疗的多变量重复测量模型。
92%的患者为女性。67%为白人，31%为非裔美国人，2%为亚洲人（所有这些群体可能包括西班牙裔）。基线时的平均值如下：年龄41.5岁，病程8.1年，SELENA - SLEDAI为3.3（中位数2，范围0 - 18），BLyS为5.57 ng/ml，IgG为1439 mg/dl，C3为104.4 mg/dl，C4为21.3 mg/dl；在抗dsDNA阳性者中，中位数滴度为1:40（范围1:10 - 1:1280）。单因素分析显示血浆BLyS水平与抗dsDNA滴度（P = 0.0465）和SELENA - SLEDAI评分（P = 0.0002）相关。在多变量分析中，与上一次就诊相比SELENA - SLEDAI评分的更大升高与上一次就诊时较高的BLyS水平相关（P = 0.0042），且与上一次就诊至本次就诊期间BLyS水平的更大升高相关（P = 0.0007）。
上一次就诊至本次就诊期间BLyS水平的更大升高与随后SELENA - SLEDAI评分的更大升高之间，以及上一次就诊时BLyS水平升高与随后更高的SELENA - SLEDAI评分之间的关联结果，证明了循环BLyS水平与SLE疾病活动度之间的关系。这些结果支持了BLyS是SLE治疗靶点候选物的观点。
