B cells in systemic lupus erythematosus: Targets of new therapies and surveillance tools

Abstract

B cell hyperactivity is a hallmark of the complex autoimmune disease systemic lupus erythematosus (SLE), which has justified drug development focusing on B cell altering agents during the last decades, as well as the off-label use of B cell targeting biologics. About a decade ago, the anti-B cell activating factor (BAFF) belimumab was the first biological agent to be licensed for the treatment of adult patients with active yet non-renal and non-neuropsychiatric SLE, to later be expanded to include treatment of pediatric SLE and, recently, lupus nephritis. B cell depletion is recommended as an off-label option in refractory cases, with the anti-CD20 rituximab having been the most used B cell depleting agent to date while agents with a slightly different binding specificity to CD20 such as obinutuzumab have also shown promise, forming a part of the current pipeline. In addition, terminally differentiated B cells have also been the targets of experimental therapies, with the proteasome inhibitor bortezomib being one example. Apart from being promising drug targets, B and plasma cells have also shown promise in the surveillance of patients with SLE, especially for monitoring B cell depleting or B cell altering therapies. Inadequate B cell depletion may signify poor expected clinical response to rituximab, for example, while prominent reductions in certain B cell subsets may signify a protection against flare development in patients treated with belimumab. Toward an era with a richer therapeutic armamentarium in SLE, including to a large extent B cell altering treatments, the challenge that emerges is to determine diagnostic means for evidence-based therapeutic decision-making, that uses clinical information, serological markers, and gene expression patterns to guide individualized precision strategies.

Cellular and Humoral Immunity and Infection Responses to SARS-CoV-2:Immune Biomolecular Mechanisms by Case Study within SARS-CoV-2 Pathogenesis and Other Infections

“…Interestingly increased Tr cells did correlate with COVID-19 disease routinely used blood protein markers detected including neutrophil/lymphocyte ratio, acute phase proteins, ferritin levels, D-dimer, and others. The exact nature of DN B cells requires further clarification, as subsets are associated with SLE [141]. As before the B Cell DN1 reduction / DN3 increase in chronic COVID-19 was accompanied by high levels of CD69 and CD89 in DN2 cells alongside what appears to be DN2 selection of IgG but also suggests that DN3 cells do produce VH4-34 IgG autoreactive antibodies [116].…”

Cellular and Humoral Immunity and Infection Responses to SARS-CoV-2:Immune Biomolecular Mechanisms by Case Study within SARS-CoV-2 Pathogenesis and Other Infections

“…Interestingly increased Tr cells did correlate with COVID-19 disease routinely used blood protein markers detected including neutrophil/lymphocyte ratio, acute phase proteins, ferritin levels, D-dimer, and others. The exact nature of DN B cells requires further clarification, as subsets are associated with SLE [138]. As before the B Cell DN1 reduction / DN3 increase in chronic COVID-19 was accompanied by high levels of CD69 and CD89 in DN2 cells alongside what appears to be DN2 selection of IgG but also suggests that DN3 cells do produce VH4-34 IgG autoreactive antibodies [113].…”

Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus

“…The level of immune cell infiltration was closely related to the progression and outcome of SLE ( 13 , 14 ). To further investigate the role of immune cell infiltration in SLE-APO, we performed a comprehensive evaluation using CIBERSORT and conducted correlation analysis between infiltrating immune cells and SEZ6 , NRAD1 , and LPAR4 .…”

“…The AUC of 0.731 based on leave-one-out cross validation (LOOCV) displayed SEZ6 had a fair predictive performance. The level of immune cell infiltration was highly linked with the progression and outcome of SLE ( 13 , 14 ). We observed significant differences in the infiltration of critical immune cells, such as plasma cells, naïve CD4 T cells, and monocytes, between the SLE patients with APO (SLE-APO) and with normal pregnancy outcome (SLE-NC) groups.…”