Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcγRIIb and CD19

Szili, Dániel; Cserhalmi, Marcell; Bankó, Zsuzsanna; Nagy, György; Szymkowski, David E.; Sármay, Gabriella

doi:10.4161/mabs.28841

Cited by 28 publications

(16 citation statements)

References 54 publications

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“…Indeed, recently an anti-CD19 antibody carrying an Fc region with over 400 times greater affinity to FcγRIIb compared to FγRIIa has been engineered ( 84 ). Co-engaging of the B-cell receptor complex together with FcγRIIb by this engineered antibody suppressed B-cell activation and function, including IgG secretion and IL-6 production ( 85 – 87 ), which therefore may be of therapeutic benefit in IgG-mediated autoimmune diseases such as RA and SLE.…”

Section: Modulation Of Fcγr-induced Cytokine Production: Opportunitiementioning

confidence: 99%

Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

et al. 2015

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Control of cytokine production by immune cells is pivotal for counteracting infections via orchestration of local and systemic inflammation. Although their contribution has long been underexposed, it has recently become clear that human Fc gamma receptors (FcγRs), which are receptors for the Fc region of immunoglobulin G (IgG) antibodies, play a critical role in this process by controlling tissue- and pathogen-specific cytokine production. Whereas individual stimulation of FcγRs does not evoke cytokine production, FcγRs cell-type specifically interact with various other receptors for selective amplification or inhibition of particular cytokines, thereby tailoring cytokine responses to the immunological context. The physiological function of FcγR-mediated control of cytokine production is to counteract infections with various classes of pathogens. Upon IgG opsonization, pathogens are simultaneously recognized by FcγRs as well as by various pathogen-sensing receptors, leading to the induction of pathogen class-specific immune responses. However, when erroneously activated, the same mechanism also contributes to the development of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In this review, we discuss control of cytokine production as a novel function of FcγRs in human innate immune cells in the context of homeostasis, infection, and autoimmunity and address the possibilities for future therapeutic exploitation.

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Section: Modulation Of Fcγr-induced Cytokine Production: Opportunitiementioning

confidence: 99%

Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

et al. 2015

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“…The mechanism of pathogenesis is not fully understood. To date, it is confirmed that citrullinated peptide autoantigens induce T-cell-mediated B cell activation [14,15]. This action leads to ACPA production by hyper-reactive B cells and activates pro-inflammatory mediators, which subsequently cause joint inflammation and erosion.…”

Section: Introductionmentioning

confidence: 92%

“…Replicated measurements, RA and HC samples, and CV values. S1 Table. Triplicate results for ELISA: RA (samples 1-10) and HC (samples [11][12][13][14][15][16][17][18][19][20]. (PDF) S2 Appendix.…”

Section: Plos Onementioning

confidence: 99%

Antibodies to synthetic citrullinated peptide epitope correlate with disease activity and flares in rheumatoid arthritis

2020

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Rheumatoid arthritis (RA), caused by the abnormal recognition of human joint cells by autoimmune antibodies, remains the world's most prevalent autoimmune disease, with over five million people affected and as much as 4% of the population at risk of RA. To prevent rapid disease development, hormonal and anti-inflammatory therapies require fast and reliable RA diagnosis. However, difficulty in detecting early specific biomarkers for RA means that it is unclear when treatment needs to begin. Here, we combined synthesis of citrullinated peptide epitopes with molecular diagnostics to verify a new specific biomarker for early RA diagnosis and flare prediction. A fibrinogen-derived 21-amino-acid-long citrullinated peptide showed high reactivity toward autoantibodies in RA samples. Additionally, the level of antibodies to this epitope was elevated prior to flares. In contrast, other citrullinated protein variants had lower reactivity and poorer sensitivity to disease activity. In conclusion, fibrinogenderived epitope E2 subjected to citrullination facilitated a reliable RA diagnosis with a strong correlation to disease activity. This is of a high value for the diagnosis and management of RA patients who respond poorly to treatment.

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“…Obexelimab (XmAb5871) is a humanized Fc-engineered antibody that binds to CD19 on the B cell surface and has a better affinity for Fcγ receptor IIb (FcγRIIb) to inhibit the function and activation of B cells ( 106 – 108 ) ( Figure 2H ). CD19 is expressed in almost all stages of B cells, because of its wide expression, the use of therapeutic antibodies against CD19 in SLE is limited ( 109 ).…”

Section: Bispecific Antibodies In Slementioning

confidence: 99%

A Comprehensive Review of Biological Agents for Lupus: Beyond Single Target

Yang

Zhao

et al. 2020

Front. Immunol.

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Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple immune cells. Due to its complex pathogenesis, the effectiveness of traditional treatment methods is limited. Many patients have developed resistance to conventional treatment or are not sensitive to steroid and immunosuppressant therapy, and so emerging therapeutic antibodies have become an alternative and have been shown to work well in many patients with moderate and severe SLE. This review summarizes the biological agents that are in the preclinical and clinical trial study of SLE. In addition to the various monoclonal antibodies that have been studied for a long time, such as belimumab and rituximab, we focused on another treatment for SLE, bispecific antibodies (BsAbs) such as tibulizumab, which simultaneously targets multiple pathogenic cytokines or pathways. Although the application of BsAbs in cancer has been intensively studied, their application in autoimmune diseases is still in the infant stage. This unique combined mechanism of action may provide a novel therapeutic strategy for SLE.

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Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcγRIIb and CD19

Cited by 28 publications

References 54 publications

Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

Control of Cytokine Production by Human Fc Gamma Receptors: Implications for Pathogen Defense and Autoimmunity

Antibodies to synthetic citrullinated peptide epitope correlate with disease activity and flares in rheumatoid arthritis

A Comprehensive Review of Biological Agents for Lupus: Beyond Single Target

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