Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance

Abstract

Abatacept, an inhibitor of CD28 mediated T-cell activation, has been shown to be effective in controlling inflammation during rheumatoid arthritis (RA). However, its effects on immune regulatory B and T cells (Bregs and Tregs) has not been fully explored. Thirty-one RA patients treated with abatacept for ≥ 6 months along with 31 RA patients treated with other modalities as well as 30 healthy controls were recruited. Of these 62 RA patient, 49 (79%) were females with a mean age of 54 ± 12 years and disease duration of 10 ± 6 years. The blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and Luminex Multiplex assay. Treatment with abatacept significantly enhanced the blood level of IL-35+ IL-10+ Bregs (P = 0.0007). Their levels were higher in the blood of remitted patients (DAS28-CRP < 2.6) compared to the unremitted ones (P = 0.0173), 6 months following abatacept treatment initiation. Moreover, abatacept treatment significantly enhanced the blood levels of LAG3+ conventional and unconventional Tregs of RA patients. This increase in the blood levels of Bregs and Tregs was accompanied with an elevated serum level of IL-35 and IFN-β in abatacept-treated patients. Therefore, Abatacept efficiency to achieve remittance in RA could be attributed, in part, to its ability to enhance immune regulatory cells, especially IL-135+ IL-10+ Bregs.

Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

“…On the other hand, abatacept, an inhibitor of CD28-mediated T cell activation, has been shown to be effective in regulating inflammation during RA. Abatacept's efficiency in achieving remittance in RA can be attributed, in part, to its ability to enhance immune regulatory cells, particularly IL-35 + IL-10 + regulatory B (Breg) cells [51].…”

Dose-dependent effects of oleuropein administration on regulatory T-cells in patients with rheumatoid arthritis: An in vitro approach

“… 13 , 14 , 53 However, the flow cytometry results showed no statistically significant difference in Treg frequencies between HC and RA patients, which might be related to the different effects of conventional and biological DMARDs on Tregs in RA patients. 54 – 57 A number of studies have shown that treatment of RA patients with some but not all of DMARDs, such as methotrexate, tumor necrosis factor-α inhibitors (TNF-αi), adalimumab, and etanercept can restore the regulatory functions of Tregs and increase the frequency of these cells through various mechanisms. 54 , 55 , 58 , 59 Therefore, the effects of OLEU on Tregs could be influenced by treatment of RA patients with various DMARDs.…”

Abatacept Promotes Regulatory B Cell Functions, Enhancing Their Ability to Reduce the Th1 Response in Rheumatoid Arthritis Patients through the Production of IL-10 and TGF-β

“…Furthermore, associations between CD24 hi CD38 hi B cells and immune regulation were noted in terms favorable clinical outcome in patients with chronic inflammatory and autoimmune diseases (36). Recently, Alenazy et al (37) reported that the abatacept treatment was responsible for an increase in the percentage of IL-10 1 IL-35 1 Breg cells in RA patients. The time frame of our study (3 mo) and theirs (6 mo) could explain that we were not able to reach statistical significance.…”