Cytokine and autoantibody clusters interaction in systemic lupus erythematosus

Journal of Translational Medicine

Research

Yhojan Rodríguez¹  Rubén D. Mantilla¹  Juliana Saavedra¹  Mónica Rodríguez-Jiménez¹  Julián Barahona-Correa¹  Manuel Rojas¹  Nicolás Molano-González¹  Juan-Manuel Anaya¹  Diana M. Monsalve¹  Yovana Pacheco¹  Carolina Ramírez-Santana¹  Yeny Acosta-Ampudia¹ 

[1] Center for Autoimmune Diseases Research (CREA) School of Medicine and Health Sciences, Universidad del Rosario, Carrera 26 # 63B-51, Bogota, Colombia;

关键词: Personalized medicine;    Autoantibodies;    Cytokines;    Systemic lupus erythematosus;    Subphenotypes;    Cluster analysis;    Antiphospholipid antibodies;    Anti-dsDNA antibodies;    Interleukin 8;    Interferon alpha;    Interleukin 12p40;    Taxonomy;   

DOI  :  10.1186/s12967-017-1345-y

 received in 2017-08-29, accepted in 2017-11-16,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundEvidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed.MethodsThis was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables.ResultsFirst, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity.ConclusionThese results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.

【 授权许可】

CC BY   
© The Author(s) 2017