B-cell critical pathways open a new era in lupus targeted therapy.

Baileyumab targets the key pathway of B cells, reduces the production of autoantibodies and preserves immunity, which opens a new era of targeted therapy for SLE.systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by multiple organ involvement and a large number of autoantibodies.with the progress and development of science and technology, the treatment of SLE is also gradually evolving and improving the outcome of SLE patients.1 traditional treatment methods make SLE treatment difficult. In 1944, Philip S. Hench, a physician at Mayo Clinic in the United States, used hormone for the first time to treat rheumatoid arthritis. Br / >thus, it can be used for the treatment of systemic lupus erythematosus.however, the side effects of hormone were quickly found: easy infection, increased blood pressure, osteoporosis, etc.in addition, although the short-term effect of corticosteroids is significant, the long-term effect on severe lupus erythematosus is very limited.the National Institutes of Health (NIH) carried out a study spanning more than 17 years in 1969. The results showed that more than 50% of subjects who used hormone alone had uremia after 10 years, and the incidence of uremia was 80% after 15 years [1,2].while hydroxychloroquine can better prevent the recurrence of SLE [3], it usually needs combined hormone therapy, and the side effects caused by long-term application of hormone are still inevitable [4].therefore, how to reduce the dosage of hormone as much as possible under the premise of effective control of SLE is the key to clinical treatment.to understand the complex pathogenesis of SLE and take targeted treatment is the most popular strategy in clinical practice.2 auto reactive B cells are the "killer" of SLE. BLyS becomes the key of treatment. When the number of apoptotic cells increases and the clearance is abnormal, it will cause secondary necrosis, then activate the immune system, produce a large number of cell fragments, release a large number of inflammatory factors, stimulate the activation of antigen-presenting cells, and stimulate the proliferation and differentiation of auto reactive B cells.however, according to the research, in the pathogenesis of SLE, the self reactive B cells almost run through the whole process of the disease [5]. Auto reactive B cells produce a large number of autoantibodies against the body's own cells and tissues, causing tissue and organ damage, which is the "killer" leading to the onset of SLE.therefore, B lymphocyte pathway is considered as the core pathway and treatment cornerstone of SLE.b lymphocyte stimulator (BLyS) is a key molecule in B cell pathway, which plays an important role in B cell maturation, proliferation and differentiation, and can be called "Star" in immunology research.the increase of BLyS level in SLE patients was related to the high titer of anti dsDNA antibody and the deterioration of SLE [5,6] (Fig. 1).Fig. 1 elevated BLyS promotes the survival of auto reactive B cells, leading to SLE deterioration. 3 targeting the key pathway of B cells, opening In the new era of SLE targeted therapy, as an all humanized IgG1 monoclonal antibody, baileyumab can selectively block the interaction between excessive BLyS and receptors (mainly BR3 receptors), inhibit the proliferation of auto reactive B cells [7], and reduce the differentiation of auto reactive B cells into plasma cells producing autoantibodies [8, 9] In order to reduce the organ damage caused by autoantibody production and immune complex deposition (Fig. 2). in the course of targeting, baileyumab can reduce BLyS with higher activity On the other hand, unlike proliferation inducing ligand (April), baileyumab suppresses BLyS and does not continuously affect the immune function of cells at the late stage (including long-term survival plasma cells and memory B cells), so as to retain humoral immunity (Fig. 3) ）。 Fig. 2 peleyumab targeted the key B cell pathway of SLE and inhibited the excessive proliferation and differentiation of auto reactive B cells The inhibition of BLyS by baileyumab does not continue to affect the cells in the late stage (including long-term survival plasma cells and memory B cells). A number of phase III and real-world studies of baileyumab have confirmed that the combination of baileyumab and conventional therapy can better control disease activity, reduce the risk of recurrence, reduce hormone dosage, reduce organ damage, and the safety and safety of baileyumab are better than those of conventional therapy Similar to placebo, the incidence of severe infection was low [12]. in conclusion, baileyumab targets the key B-cell pathway, reduces the generation of autoantibodies and preserves immunity, which opens a new era of targeted therapy for SLE. combined with the key medical contents of this issue, which of the following statements do you think is correct? B lymphocyte stimulating factor (BLyS) is a key molecule in B cell pathway, which plays an important role in the process of B cell maturation, proliferation and differentiation. C. baileyumab can specifically block the binding of soluble BLyS with receptors on B cells, and induce it More auto reactive B cell apoptosis D. baileyumab can be used in the treatment of systemic lupus erythematosus, which can control disease activity, reduce hormone dosage and recurrence risk, reduce organ damage, and its safety is similar to placebo. The incidence of severe infection is low. Slide left to see the answer ~ correct answer: ABCD reference: 1. Steinberg ad. the treatment of lupus nephritis. Kidney Int. 1986; 30: 769.2. Gourley MF, Austin HA 3rd, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 1996; 125: 549.3. Canadian Hydroxychloroquine Study Group. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med. 1991; 324: 150.4. Bevra Hannahs Hahn, Zhang J, et al. J. immune, 2001, 166 (1): 6-10.6. Petri m, et al. Arthritis rheum, 2008, 58 (8): 2453-2459.7. Cancro MP, et al. J. Clin. Invest. 2009; 119: 1066‒1073.8. Dennis GJ. Clinical pharmacology & Therapeutics. 2012; 91(1): 143-149.9. Dorner T, et al. Pharmacology & Therapeutics. 2010; 125: 464‒475.10. Shin W, et al. Nature Communications.2018; 9: 1200.11. Collins C E, Dall'Era M, Kan H, et al. Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA[J]. Lupus Sci Med. 2015; 3 (1): e000118.pm-cn-bel-nltr-200011, due March 2022. This material is not an advertisement. It is intended to provide scientific information to and only for healthcare professionals. If you are not a healthcare professional, please do not read or disseminate the content - end love me, please give it to me!