期刊论文详细信息
Frontiers in Immunology
A Cross-Sectional and Longitudinal Study to Define Alarmins and A-SAA Variants as Companion Markers in Early Rheumatoid Arthritis
Valérie Badot1  Silvana Di Romana2  Patrick Durez3  Tatiana Sokolova3  Paschalis Sidiras4  Gwenaël Nys5  Marianne Fillet5  Federica Ciregia6  Gaël Cobraiville6  Dominique de Seny6  Michel G. Malaise6 
[1] Department of Rheumatology, Centre Hospitalier Universitaire (CHU) Brugmann, Bruxelles, Belgium;Department of Rheumatology, Centre Hospitalier Universitaire (CHU) Saint–Pierre, Bruxelles, Belgium;Department of Rheumatology, Cliniques Universitaires Saint–Luc, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Bruxelles, Belgium;Department of Rheumatology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium;Laboratory for the Analysis of Medicines, Centre Interdisciplinaire De Recherche Sur Le Médicament (CIRM), Department of Pharmacy, University of Liège, Liège, Belgium;Laboratory of Rheumatology, University of Liège, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium;
关键词: early RA;    A-SAA variants;    alarmins;    DMARDs;    companion markers;   
DOI  :  10.3389/fimmu.2021.638814
来源: DOAJ
【 摘 要 】

Nowadays, in the study of rheumatoid arthritis (RA), more and more interest is directed towards an earlier effective therapeutic intervention and the determination of companion markers for predicting response to therapy with the goal to prevent progressive joint damage, deformities, and functional disability. With the present work, we aimed at quantifying in a cohort of early RA (ERA) patients naïve to DMARD therapy, proteins whose increase was previously found associated with RA: serum amyloid A (A-SAA) and alarmins. Five A-SAA variants (SAA1α, SAA1β, SAA1γ, SAA2α, and SAA2β) but also S100A8 and S100A9 proteins were simultaneously quantified in plasma applying a method based on single targeted bottom-up proteomics LC-MS/MS. First, we compared their expression between ERA (n = 100) and healthy subjects (n = 100), then we focused on their trend by monitoring ERA patients naïve to DMARD treatment, 1 year after starting therapy. Only SAA1α and SAA2α levels were increased in ERA patients, and SAA2α appears to mostly mediate the pathological role of A-SAA. Levels of these variants, together with SAA1β, only decreased under biologic DMARD treatment but not under methotrexate monotherapy. This study highlights the importance to better understand the modulation of expression of these variants in ERA in order to subsequently better characterize their biological function. On the other hand, alarmin expression increased in ERA compared to controls but remained elevated after 12 months of methotrexate or biologic treatment. The work overcomes the concept of considering these proteins as biomarkers for diagnosis, demonstrating that SAA1α, SAA1β, and SAA2α variants but also S100A8 and S100A9 do not respond to all early treatment in ERA and should be rather considered as companion markers useful to improve the follow-up of treatment response and remission state. Moreover, it suggests that earlier use of biologics in addition to methotrexate may be worth considering.

【 授权许可】

Unknown   

  文献评价指标  
  下载次数:0次 浏览次数:0次