Targeted therapies for lupus nephritis: Current perspectives and future directions / 中华医学杂志(英文版)

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

Inhibition of nerve transplantation rejection in adult mice induced by intrathymic injection of allogeneic antigen / 中国组织工程研究

BACKGROUND: Uncoupling of major histocompatibility complex (MHC) is the main cause for transplantation rejection, and it is the best way to prevent transplantation rejection by induce immunological tolerance of the recipient to the donor organ. Self-tolerant T cells can be obtained by negative selection in thymus, whether the intrathymic injection of allogenic antigen can get the immunological tolerance to the antigen?OBJECTIVE: To observe the effects of intrathymic injection of allogenic antigen on inducing immunological tolerance in nerve transplantation.DESIGN: A comparative observation.SETTINGS: Department of Immunology, Harbin Medical University; Department of Orthopaedics, Fourth Clinical Hospital of Harbin Medical University.MATERIALS: Thirty donor C57BL/6 mice (H-2b), male, aged from 6-8 weeks, weighing 18-22 g, were purchased from the Veterinarian Institute of Heilongjiang Province; While 60 recipient Balb/c mice (H-2b) female, aged from 6-8 weeks, weighing 18-22 g, from Beijing Experimental Animal Center. MHC (H-2b) antigen was prepared by the Department of Immunology, Harbin Medical University, and the concentration of protein was 4.4 g/L.METHODS: The experiments were carried out in the Department of Immunology, Harbin Medical University from June to November 2002. The recipient Balb/c mice were randomly divided into four groups: intrathymic injection group, syngenic transplantation group, allogenic transplantation group and immunosuppressant drug group. MHC (H-2b) antigen was extracted from splenic cells of donor C57BL/6 mice and injected intrathymically into recipient Balb/c mice (H-2d). Two weeks later, the sciatic nerve was transplanted to the recipient mice. Mixed lymphocyte reaction and delayed-type hypersensitivity (DTH) were detected at 3 weeks after transplantation.MAIN OUTCOME MEASURES:The differences of mixed lymphocyte reaction and DTH were compared among the groups.RESULTS: All the 30 donor C25BL/6 mice (H-2b) and 60 recipient Balb/c mice (H-2d) were involved in the analysis of results.①Results of mixed lymphocyte reaction: The cell proliferations in the syngenic transplantation group and intrathymic injection group were obviously lower than that in the allogenic transplantation group [(546.1±75.1), (2 668.3±533.8), (3 101.3±429.1), (4 312.3±534.1) minutes-1, P＜0.05].②Results of DTH: The thicknesses difference between two pads in the syngenic transplantation group and intrathymic injection group were obviously lower than that in the allogenic transplantation group [(41.1±3.7), (72.1±5.1), (57.6±11.3), (86.2±13.2)μm, P＜0.05].CONCLUSION:The intrathymic injection of donor H-2b antigen could induce immunological tolerance of nerve transplantation.