不同的IgM和IgG自身抗体特征描述了不完全和分类的系统性自身免疫性疾病

Distinct IgM and IgG autoantibody profiles characterize incomplete and classified systemic autoimmune diseases.

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摘要(中文译文)

不完全性红斑狼疮(ILE)和非干燥病性干燥症(nSjD-sicca)是临床上具有异质性的、分类不完全的自身免疫性疾病,分别与系统性红斑狼疮(SLE)和干燥病(SjD)存在共同特征。尽管部分患者进展为已分类疾病,但许多患者保持稳定状态。区分不完全性与已确立自身免疫病的免疫学特征仍不明确。本研究旨在通过扩展自身抗体谱分析,表征并比较ILE、SLE、nSjD-sicca和SjD之间的自身抗体免疫特征。血清样本来自ILE患者(n=80)、SLE患者(n=80)、nSjD-sicca患者(n=52)、SjD患者(n=60)以及匹配的健康对照者(n=79)。初步筛查采用Bio-Rad BioPlex 2200进行。扩展谱分析使用GeneCopoeia人类自身免疫阵列(120种自身抗原),同步检测IgM和IgG。传统筛查显示了预期模式:ILE(抗nRNP 26.3%;抗染色质25.0%)、SLE(抗SmRNP 40.0%;抗dsDNA 31.3%)、nSjD-sicca(抗La 9.6%)和SjD(抗Ro/SSA 53.3%)。扩展分析显示,与SLE相比,ILE中IgM自身反应性显著增高(BH-FDR校正p<0.05),靶向核抗原(KU、Nup62、CENP-A/B)、细胞因子(IFN-α1、IFN-ϵ、IL-15、GM-CSF)、线粒体抗原(M2)、细胞外基质(IV型胶原、纤维蛋白原)、血管抗原(β2-糖蛋白I、AGTR)及肠道相关抗原(组织转谷氨酰胺酶、内因子)。相比之下,SLE表现出对经典核抗原(包括核心组蛋白和dsDNA)的IgG应答富集。在干燥症谱系内,与nSjD-sicca相比,SjD中Ro52(TRIM21)IgG自身抗体显著增高。这些发现表明,不完全性自身免疫病状态呈现以IgM为主的独特自身抗体谱,而非仅仅是已分类疾病中IgG优势应答的减弱版本,突显了同种型特异性谱分析在疾病分类中的潜在价值。

Abstract

Incomplete lupus erythematosus (ILE) and non-Sjögren's disease sicca (nSjD-sicca) are clinically heterogeneous, incompletely classified autoimmune conditions that share features with systemic lupus erythematosus (SLE) and Sjögren's disease (SjD), respectively. Although some patients progress to classified disease, many remain stable. The immunologic features distinguishing incomplete from established autoimmune disease remain poorly defined. We sought to characterize and compare autoantibody immune signatures across ILE, SLE, nSjD-sicca, and SjD using expanded autoantibody profiling. Serum samples were obtained from patients with ILE (n=80), SLE (n=80), nSjD-sicca (n=52), SjD (n=60), and matched healthy controls (n=79). Initial screening was performed using the Bio-Rad BioPlex 2200. Expanded profiling utilized the GeneCopoeia Human Autoimmune Array (120 autoantigens) with parallel IgM and IgG detection. Traditional screening demonstrated expected patterns: ILE (anti-nRNP 26.3%; anti-chromatin 25.0%), SLE (anti-SmRNP 40.0%; anti-dsDNA 31.3%), nSjD-sicca (anti-La 9.6%), and SjD (anti-Ro/SSA 53.3%). Expanded analysis revealed significantly increased IgM autoreactivity in ILE compared with SLE (BH-FDR-adjusted p<0.05), targeting nuclear (KU, Nup62, CENP-A/B), cytokine (IFN-α1, IFN-ϵ, IL-15, GM-CSF), mitochondrial (M2), extracellular matrix (collagen IV, fibrinogen), vascular (β2-glycoprotein I, AGTR), and gut-associated antigens (tissue transglutaminase, intrinsic factor). In contrast, SLE demonstrated enriched IgG responses to canonical nuclear antigens, including core histone and dsDNA. Within the sicca spectrum, Ro52 (TRIM21) IgG autoantibodies were significantly increased in SjD compared to nSjD-sicca. These findings indicate that incomplete autoimmune disease states exhibit distinct IgM-dominant autoantibody profiles rather than simply attenuated versions of the IgG dominant responses in classified disease, highlighting the potential value of isotype-specific profiling for disease classification.

如何引用

AMA

Rebecca A Wood, Neha Kodali, Nancy Redinger, A Darise Farris, Christopher J Lessard, R Hal Scofield. Distinct IgM and IgG autoantibody profiles characterize incomplete and classified systemic autoimmune diseases.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1847217.

APA

Rebecca A Wood, Neha Kodali, Nancy Redinger, A Darise Farris, Christopher J Lessard, R Hal Scofield (2026). Distinct IgM and IgG autoantibody profiles characterize incomplete and classified systemic autoimmune diseases.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1847217

GB/T 7714

Rebecca A Wood, Neha Kodali, Nancy Redinger, A Darise Farris, Christopher J Lessard, R Hal Scofield. Distinct IgM and IgG autoantibody profiles characterize incomplete and classified systemic autoimmune diseases.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1847217.

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