Weckerle Corinna E, Franek Beverly S, Kelly Jennifer A, Kumabe Marissa, Mikolaitis Rachel A, Green Stephanie L, Utset Tammy O, Jolly Meenakshi, James Judith A, Harley John B, Niewold Timothy B
University of Chicago, Chicago, IL, USA.
Arthritis Rheum. 2011 Apr;63(4):1044-53. doi: 10.1002/art.30187.
Interferon-α (IFNα) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFNα levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. This study was undertaken to detect associations between clinical and serologic disease manifestations and serum IFNα activity in a large diverse SLE cohort, using multivariate and network analyses.
We studied 1,089 SLE patients (387 African American, 186 Hispanic American, and 516 European American patients). The presence or absence of individual American College of Rheumatology (ACR) clinical criteria for SLE, autoantibodies, and serum IFNα activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each ancestral background group separately to establish the network of associations between variables that were independently significant following Bonferroni correction.
In all ancestral backgrounds, high IFNα activity was associated with anti-Ro and anti-double-stranded DNA antibodies (P = 4.6 × 10(-18) and P = 2.9 × 10(-16) , respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFNα activity (P ≤ 6.7 × 10(-4) ). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared among >1 ancestral background. Associations between clinical criteria were different for different ancestral backgrounds, while autoantibody-IFNα relationships were similar across backgrounds. IFNα activity and autoantibodies were not associated with ACR clinical features in multivariate models.
Our findings indicate that serum IFNα activity is strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFNα may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations.
α干扰素（IFNα）是系统性红斑狼疮（SLE）的主要致病因素，高IFNα水平可能与特定临床表现相关。个体临床和血清学特征的患病率因种族不同而有显著差异。本研究旨在通过多变量和网络分析，检测一个大型多样化SLE队列中临床和血清学疾病表现与血清IFNα活性之间的关联。
我们研究了1089例SLE患者（387例非裔美国人、186例西班牙裔美国人、516例欧洲裔美国人）。在单变量和多变量模型中分析了美国风湿病学会（ACR）SLE临床标准、自身抗体的存在与否以及血清IFNα活性数据。在每个种族背景组中分别进行迭代多变量逻辑回归，以建立经Bonferroni校正后具有独立显著性的变量之间的关联网络。
在所有种族背景中，高IFNα活性与抗Ro和抗双链DNA抗体相关（分别为P = 4.6×10⁻¹⁸和P = 2.9×10⁻¹⁶）。较年轻的年龄、非欧洲血统和抗RNP也与血清IFNα活性增加独立相关（P≤6.7×10⁻⁴）。我们在网络分析中发现了变量之间的14种独特关联，其中只有7种关联在超过1个种族背景中共享。不同种族背景的临床标准之间的关联不同，而自身抗体与IFNα的关系在各背景中相似。在多变量模型中，IFNα活性和自身抗体与ACR临床特征无关。
我们的研究结果表明，血清IFNα活性与自身抗体密切且一致相关，而与SLE的临床特征无独立关联。IFNα可能与体液耐受和初始发病机制比与后期临床疾病表现更相关。
