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...
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doaj-947ebe4548714661b13f3501c3da00992021-03-11T12:26:22ZengNature Publishing GroupScientific Reports2045-23222021-03-011111910.1038/s41598-021-83615-0Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittanceMaha Fahad Alenazy0Fatemeh Saheb Sharif-Askari1Mohammed A. Omair2Mohammad S. El-Wetidy3Maha A. Omair4Hussam Mitwalli5Saleh Al-Muhsen6Abeer Al-Masri7Qutayba Hamid8Rabih Halwani9Immunology Research Lab, College of Medicine, King Saud UniversitySharjah Institute of Medical Research, University of SharjahRheumatology Unit, Department of Medicine, College of Medicine, King Saud UniversityImmunology Research Lab, College of Medicine, King Saud UniversityDepartment of Statistics and Operations Research, College of Science, King Saud UniversityImmunology Research Lab, College of Medicine, King Saud UniversityImmunology Research Lab, College of Medicine, King Saud UniversityDepartment of Physiology, College of Medicine, King Saud UniversitySharjah Institute of Medical Research, University of SharjahSharjah Institute of Medical Research, University of SharjahAbstract 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.https://doi.org/10.1038/s41598-021-83615-0 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maha Fahad Alenazy Fatemeh Saheb Sharif-Askari Mohammed A. Omair Mohammad S. El-Wetidy Maha A. Omair Hussam Mitwalli Saleh Al-Muhsen Abeer Al-Masri Qutayba Hamid Rabih Halwani |
spellingShingle |
Maha Fahad Alenazy Fatemeh Saheb Sharif-Askari Mohammed A. Omair Mohammad S. El-Wetidy Maha A. Omair Hussam Mitwalli Saleh Al-Muhsen Abeer Al-Masri Qutayba Hamid Rabih Halwani Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance Scientific Reports |
author_facet |
Maha Fahad Alenazy Fatemeh Saheb Sharif-Askari Mohammed A. Omair Mohammad S. El-Wetidy Maha A. Omair Hussam Mitwalli Saleh Al-Muhsen Abeer Al-Masri Qutayba Hamid Rabih Halwani |
author_sort |
Maha Fahad Alenazy |
title |
Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance |
title_short |
Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance |
title_full |
Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance |
title_fullStr |
Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance |
title_full_unstemmed |
Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance |
title_sort |
abatacept enhances blood regulatory b cells of rheumatoid arthritis patients to a level that associates with disease remittance |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
description |
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. |
url |
https://doi.org/10.1038/s41598-021-83615-0 |
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