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May 10, 2025 marks the 22nd World Lupus Day. According to a 2023 meta-analysis, an estimated 3.41 million people worldwide are living with Systemic Lupus Erythematosus (SLE).
Overview of SLE Pathology and Physiology
SLE is a complex chronic autoimmune connective tissue disease, characterized by the immune system mistakenly attacking the body’s own healthy tissues, leading to multi-organ involvement. It is more prevalent in women, especially those of childbearing age between 20 and 40. Early symptoms are often non-specific, including fever, fatigue, weight loss, hair loss, rashes, cold-induced color changes in the hands and feet, and recurrent oral ulcers. As the disease progresses, it can affect the skin, joints, kidneys, heart, lungs, and nervous system, resulting in widespread inflammation and organ damage. While SLE currently has no cure, existing treatments can effectively manage symptoms and slow disease progression. However, most are non-specific small molecule drugs with common side effects. As a result, developing safer, more targeted therapies based on novel mechanisms has become a major focus for global research institutions and pharmaceutical companies.
We have developed a comprehensive product portfolio including highly active recombinant proteins, functional cell lines, and inhibitor screening kits. Our solutions span the entire drug development continuum – from target discovery and validation, candidate drug screening and development to CMC manufacturing and quality control – accelerating the efficient translation of SLE innovative therapies from foundational research to clinical implementation.
In the early stages of SLE, autoreactive B cells evade immune tolerance checkpoints and mature with the help of T cells, producing autoantibodies against self-antigens. These antibodies bind to antigens, forming immune complexes that further activate dendritic cells (DCs), phagocytes, and plasmacytoid dendritic cells (pDCs), leading to the release of large amounts of cytokines and chemokines, which trigger multi-organ and systemic inflammatory responses. At the same time, these inflammatory mediators feedback to activate more autoreactive T and B cells, creating a sustained cycle of immune dysregulation and inflammation.
Production and Expression of B Cell-Related Markers 1
Currently, common clinical targets for B cell-specific therapies primarily include B cell surface antigens, B cell-related cytokines, and their co-receptors, such as:
• CD19 (B-lymphocyte antigen CD19): CD19 is a key molecule in B cell development, widely expressed from pre-B cells to plasma cells. In SLE, CD19 plays a crucial role in disease initiation and progression by regulating B cell activation and proliferation. Targeting CD19 can effectively suppress abnormal B cell function and eliminate plasma cells that secrete autoantibodies, reducing immune complex formation and alleviating inflammation.
• CD20 (B-lymphocyte antigen CD20): CD20 is a transmembrane phosphoprotein primarily expressed on the surface of B lymphocytes. In SLE, targeting CD20 reduces autoantibody production by mediating the removal of B cells, thus alleviating the inflammatory response. As CD20 is not expressed on plasma cells, targeting it can suppress pathogenic B cells while preserving antibody-producing function, offering a selective therapeutic option.
• CD22 (Sialic Acid Binding Ig-like Lectin 2): CD22 is an inhibitory co-receptor on B cell membranes that regulates the B cell receptor complex. It plays an important role in SLE therapy. Targeting CD22 can enhance B cell tolerance, inhibit their abnormal activation and excessive proliferation, and reduce autoantibody production, helping to alleviate immune responses and tissue damage in SLE.
• CD38 (Lymphocyte differentiation antigen CD38): CD38 is highly expressed on the surface of plasmablasts and plasma cells, which produce large amounts of autoantibodies in SLE. Targeting CD38 effectively inhibits plasma cell function and reduces autoantibody production, thereby alleviating immune responses and inflammation in SLE.
• BAFF (B cell-activating factor) and APRIL (A Proliferation-Inducing Ligand): Both BAFF and APRIL are members of the TNF family, regulating B cell homeostasis. They promote B cell survival, differentiation, and antibody production by binding to B cell receptors BAFFR, TACI, and BCMA, playing a crucial role in autoimmune diseases. In SLE, serum BAFF levels are positively correlated with disease activity.
• BCMA (B cell maturation antigen): BCMA is mainly expressed on the surface of mature B cells and plasma cells. Targeting BCMA effectively eliminates long-lived plasma cells that produce autoantibodies. Emerging strategies like CAR-T cell therapy use BCMA recognition to precisely target pathogenic B cell populations, showing promising and durable efficacy in SLE treatment.
In SLE, the imbalance of pathogenic T cells leads to abnormal regulation of B cells by T cells, which is a key factor in immune system dysregulation, autoantibody production, and tissue damage. Under normal conditions, T cells, especially CD4+ T cells, regulate B cell activation and antibody production through controlled co-stimulatory signals and cytokines.
CD4+ T Cell Subsets Associated with SLE 2
However, in SLE, this regulatory relationship is disrupted, manifesting in multiple pathogenic mechanisms.
• Providing Co-stimulatory Signals: CD4+ T cells, particularly T follicular helper (Tfh) cells, express high levels of CD40L (Tumor necrosis factor receptor superfamily member 5 Ligand) in SLE, which binds to CD40 (Tumor necrosis factor receptor superfamily member 5) on the surface of B cells. This interaction is a critical signal for B cell activation, enhanced antigen presentation, and class switching of immunoglobulins. Continuous activation of this axis can lead to excessive B cell activation and evasion of tolerance mechanisms.
• Cytokine Secretion: IL-21 (Interleukin-21) secreted by Tfh cells is a key factor in maintaining B cell activation and plasma cell differentiation. It also promotes the clonal expansion of autoreactive B cells.
• Other Co-stimulatory Signals: T cells also enhance interactions with B cells through co-stimulatory molecules like ICOS (Inducible T-cell COStimulator) – ICOS Ligand and OX40 (Tumor necrosis factor receptor superfamily member 4) - OX40 Ligand, further increasing B cell antibody production.
• T Cell Dysfunction: In SLE, an abnormal increase in Tfh cells can impair the function of regulatory T cells (including Tregs), leading to a lack of inhibition on B cell activation, which in turn promotes the production of autoantibodies.
Additionally, the cytotoxic function of CD8+ T cells plays a significant role in the progression of SLE. They directly attack and damage self-cells by releasing cytotoxic molecules such as perforin and granzymes, and exacerbate inflammation by secreting cytokines, including IFN-γ (Interferon-gamma), further contributing to organ damage.
SLE is a disease with highly diverse clinical manifestations, affecting multiple organ systems. Due to significant differences in the pathological mechanisms and immune characteristics among patients, it is challenging to develop a unified treatment plan. This also increases the complexity of patient selection and efficacy evaluation in the development of new drugs.
Progress in SLE Biologic Drug Development (Data Source: Pharmacodia)
In recent years, with the rapid development of technologies such as detailed immune phenotyping, genome-wide association studies (GWAS), single-cell sequencing, multi-omics integration, and gene editing, researchers have significantly deepened their understanding of the pathogenesis of SLE. These cutting-edge technologies have not only revealed the heterogeneous nature of SLE but also propelled the exploration of novel therapeutic strategies, including interventions targeting immune cells, co-stimulatory molecules, cytokines, and signaling pathways. Currently, various treatment approaches have entered clinical research, including monoclonal antibodies, small molecule inhibitors, and chimeric antigen receptor T-cell (CAR-T) immunotherapies. Among them, the targeted therapies Belimumab and Anifrolumab have been approved for the treatment of moderate to severe SLE, particularly for refractory cases with poor response to conventional therapies. The approval of these two drugs has significantly increased clinical confidence and expanded treatment options for SLE.
As our understanding of the heterogeneity of SLE deepens, coupled with ongoing innovations in immunology and biotechnology, the treatment outlook for SLE is steadily improving. In the past, it was a difficult-to-cure autoimmune disease that caused damage to multiple parts of the body and systems. However, with advancements in targeted therapies and immunotherapies, SLE is now moving towards being manageable and treatable condition. These innovative treatments not only help alleviate symptoms but also delay disease progression, offering global patients better quality of life and the possibility of long-term management.
ACROBiosystems has developed a comprehensive product portfolio including highly active recombinant proteins, functional cell lines, and inhibitor screening kits. Our solutions span the entire drug development continuum – from target discovery and validation, candidate drug screening and development to CMC manufacturing and quality control – accelerating the efficient translation of SLE innovative therapies from foundational research to clinical implementation.
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1. Stockfelt, M., Teng, Y.K.O. & Vital, E.M. Opportunities and limitations of B cell depletion approaches in SLE. Nat Rev Rheumatol 21, 111–126 (2025). https://doi.org/10.1038/s41584-024-01210-9
2. T Cells in Systemic Lupus Erythematosus Paredes, Jacqueline L. et al. Rheumatic Disease Clinics, Volume 47, Issue 3, 379 - 393
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