Background

Autoimmune diseases comprise a spectrum of illnesses and are on the rise worldwide. Although antinuclear antibodies (ANAs) are detected in many autoimmune diseases, up to 20% of healthy women are ANA-positive (ANA+) and most will never develop clinical symptoms. Furthermore, disease transition is higher among ANA+ African Americans compared with ANA+ European Americans.

Objective

We sought to determine the immune features that might define and prevent transition to clinical autoimmunity in ANA+ healthy individuals.

Methods

We comprehensively phenotyped immune profiles of African Americans and European Americans who are ANA-negative (ANA−) healthy, ANA+ healthy, or have SLE using single cell mass cytometry, next-generation RNA-sequencing, multiplex cytokine profiling, and phospho-signaling analyses.

Results

We found that, compared with both ANA− and ANA+ healthy individuals, patients with SLE of both races displayed T-cell expansion and elevated expression of type I and II interferon pathways. We discovered a unique immune signature that suggests a suppressive immune phenotype and reduced CD11C⁺ autoimmunity-associated B cells in healthy ANA+ European Americans that is absent in their SLE or even healthy ANA− counterparts, or among African American cohorts. In contrast, ANA+ healthy African Americans exhibited elevated expression of T-cell activation markers and higher plasma levels of IL-6 than did healthy ANA+ European Americans.

Conclusions

We propose that this novel immune signature identified in ANA+ healthy European Americans may protect them from T-cell expansion, heightened activation of interferon pathways, and disease transition.

中文翻译：

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狼疮风险较低的自身抗体阳性健康个体表现出独特的免疫内型。

背景

自身免疫性疾病包括一系列疾病，并且在全球范围内呈上升趋势。尽管在许多自身免疫性疾病中检测到抗核抗体 (ANA)，但高达 20% 的健康女性是 ANA 阳性 (ANA+)，并且大多数永远不会出现临床症状。此外，与 ANA+ 欧洲裔美国人相比，ANA+ 非裔美国人的疾病转移率更高。

客观的

我们试图确定可能定义和阻止 ANA+ 健康个体向临床自身免疫转变的免疫特征。

方法

我们使用单细胞群流式细胞术、下一代 RNA 测序、多重细胞因子分析和磷酸化信号分析对 ANA 阴性 (ANA-) 健康、ANA+ 健康或患有 SLE 的非裔美国人和欧洲裔美国人的免疫谱进行了全面表型分析.

结果

我们发现，与 ANA- 和 ANA+ 健康个体相比，两个种族的 SLE 患者均表现出 T 细胞扩增以及 I 型和 II 型干扰素通路的表达升高。我们发现了一种独特的免疫特征，表明健康的 ANA+ 欧洲裔美国人存在抑制性免疫表型和减少的 CD11C ⁺自身免疫相关 B 细胞，而这在 SLE 甚至健康的 ANA- 对应人群中或非裔美国人队列中不存在。相比之下，ANA+ 健康的非洲裔美国人与健康的 ANA+ 欧洲裔美国人相比，T 细胞活化标志物的表达升高，IL-6 的血浆水平更高。

结论

我们提出，在 ANA+ 健康的欧洲裔美国人中发现的这种新型免疫特征可以保护他们免受 T 细胞扩增、干扰素途径的增强激活和疾病转变的影响。