THU0028 Interleukin-6 receptor inhibition, as first-line b-dmard, affects b cell subpopulations distribution through epigenetic modifications in rheumatoid arthritispatients
| Autor: | Barbara Tolusso, Elisa Gremese, Luca Petricca, Stefano Alivernini, Anna Laura Fedele, Maria Rita Gigante, C. Di Mario, G. F. Ferraccioli, G. Di Sante |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty biology business.industry Endogeny Stimulation medicine.disease Immunoglobulin D CD19 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Endocrinology immune system diseases Rheumatoid arthritis Internal medicine Interleukin-6 receptor medicine biology.protein business Homeostasis B cell |
| Zdroj: | THURSDAY, 14 JUNE 2018. |
| DOI: | 10.1136/annrheumdis-2018-eular.4809 |
| Popis: | Background Despite IL-6R inhibition was found to influence B cell subpopulations distribution in Rheumatoid Arthritis (RA), no data are available on the effect on epigenetic signature of RA B cells by this treatment. It is well known that B cell maturation is under control of the microRNA-155 (miR-155)/PU.1 axis significantly influenced by IL-6 stimulation 1 . Objectives To investigate the effect of IL-6R inhibition on the epigenetic signature of B cells (miR-155/PU.1 axis) in RA patients. Methods Twenty-nine RA patients [18 (62.1%) female; 57.2±14.9 years old; disease duration 1.3±0.7 years] starting IL-6R inhibitor treatment as first b-DMARD, have been enrolled. At study entry and after 3–6–12–18 months follow-up, CD19 + cells were isolated from peripheral blood (PB) by magnetic microbeads (Miltenyi) and B cells subpopulations were assessed through FACS according to the IgD/CD27 classification. MiR-155 and PU.1 endogenous expression was determined in PB-derived CD19 + cells by RT-PCR at baseline and after 3–6–12–18 months follow-up. IL-6 plasma level was assessed by ELISA at study entry for each patient. ACR/EULAR criteria were used to assess the response rate to IL-6R inhibitor treatment for each RA patient. PB-derived CD19 + cells of healthy individuals (HC) were used as comparison group. Results At study entry, RA patients showed higher percentage of IgD - /CD27 - CD19 + cells (p + /CD27 + CD19 + cells (p - /CD27 - CD19 + cells percentage directly correlated with Disease Activity Score (p=0.04) and IL-6 plasma levels (p=0.06) in RA patients. IL-6R inhibition lead to DAS and SDAI remission achievement in 73.9% and 52.2% of RA patients after 18 months follow-up, respectively, and significantly reduced IgD - /CD27 - CD19 + cells percentage after 18 months follow-up (p - /CD27 - CD19 + cells percentage compared to patients not achieving this outcome (p - /CD27 - CD19 + cells percentage comparable to HC (p>0.05). Analysing the epigenetic profile in B cells of RA patients, at baseline, PB-derived CD19 + cells of RA patients showed significantly higher endogenous expression of miR-155 (p=0.04) than HC. Moreover, RT-PCR showed that IL-6R inhibition significantly represses endogenous miR-155 expression in PB-derived RA B cells already after 3 months of treatment (p Conclusions IL-6R inhibitor, used as first b-DMARD treatment, acts restoring B cells homeostasis through epigenetic modulation in RA. In particular, IL6-R inhibition significantly represses endogenous expression of miR-155 in PB-derived CD19 + cells conversely restoring PU.1 expression mirrored by the decrease of IgD - /CD27 - B cell rate in RA patients achieving disease remission. Reference [1] Alivernini S, Kurowska-Stolarska M, Tolusso B, et al. Nat Commun2016. Disclosure of Interest None declared |
| Databáze: | OpenAIRE |
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