Autoreactive B-lymphocytes in SLE and RA patients: Isolation and characterisation using extractable nuclear and citrullinated antigens bound to immunobeads.

de la Varga-Martínez, RaquelRodríguez-Bayona, BeatrizCampos-Caro, AntonioAñez, Gustavo AMedina-Varo, FermínRodríguez, Carmen2023-01-252023-01-252019-04-02http://hdl.handle.net/10668/13736Systemic lupus erythematosus and rheumatoid arthritis are autoimmune diseases characterised by B-cell hyperactivation and production of autoantibodies (AutoAbs) against various self-antigens, including extractable nuclear antigens and citrullinated peptides. Therefore, B lymphocytes and antibody-secreting cells are considered relevant targets for therapies. However, isolation and characterisation of auto-reactive specific B lymphocytes are limited, primarily due to technical issues. In this work, we purified extractable nuclear antigen-specific and citrullinated peptide-specific auto-reactive B lymphocytes by magnetic selection with ENA- and citrullinated peptide-bound immunobeads. We obtained blood auto-reactive B lymphocytes from most patients. Their nature was primarily naïve B cells, some of them in an active status, with low levels of somatic hypermutations in the immunoglobulin heavy-chain variable regions. Their presence correlated with serum levels of autoAb. Auto-reactive B lymphocytes were able to differentiate into auto-reactive antibody-secreting cells under conditions of stimulation. In addition, based on the presence of circulating auto-reactive B cells and/or antibody-secreting cells, four different profiles were described in lupus patients. Thus, tracking auto-reactive B cells and/or antibody-secreting cells in patient blood could represent a biomarker for deciding whether to use therapies blocking either B cells, plasma cells or both, as well as a new tool for monitoring minimal residual autoimmune disease in patients.enB cellscitrullinated peptiderheumatoid arthritissystemic lupus erythematosusAdolescentAdultAgedAntigens, NuclearArthritis, RheumatoidAutoantigensB-LymphocytesBiomarkersCells, CulturedCitrullinationFemaleHumansImmunomagnetic SeparationLupus Erythematosus, SystemicMaleMiddle AgedProtein BindingYoung AdultAutoreactive B-lymphocytes in SLE and RA patients: Isolation and characterisation using extractable nuclear and citrullinated antigens bound to immunobeads.research article30893475open access10.1002/eji.2018480651521-4141https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eji.201848065