Systemic lupus erythematosus (SLE) is a diffuse, systemic autoimmune disorder that can impact multiple organs and systems, with patients exhibiting abnormal levels of various autoantibodies and immune markers in their serum. It is currently understood that dysregulation of B cells activation plays a pivotal role in the pathogenesis of SLE, as aberrantly activated B cells produce autoantibodies that inflict damage on multiple organs through complement activation and antibody-dependent cell-mediated cyto-toxicity. Traditional therapies for SLE may prove ineffective for certain patients or lead to adverse reactions. In most instances, conventional treatment merely alleviates symptoms and necessitates lifelong immunotherapy. A limited number of clinical cases have explored chimeric antigen receptor T cells (CAR-T) therapy as a potential treatment for autoimmune diseases such as SLE. Research indicates that CAR-T can specifically target CD19 expressed on the surface of B cells and plasma cells, achieving profound depletion while minimizing drug-related side effects. This report details a female patient diagnosed with SLE and lupus nephritis who was successfully treated using dual-targeting B cells maturation antigen CAR-T by our research team; following treatment, she ceased steroid and immunomodulator use, attaining sustained remission without these medications. The patient was a 23-year-old female. Multiple examinations in other hospitals and in our hospital showed positive anti-double-stranded DNA (dsDNA) antibody and low complement C3. Renal biopsy in our hospital showed lupus nephritis Ⅳ-G (A/C), and National Institutes of Health (NIH) activity index (AI) score=4. She was diagnosed with "SLE, lupus nephritis (LN)". She was treated with hormones, immunosuppressants and Chinese medicine, but the effect was not good. After the CAR-T treatment, She stopped using hormones and immune agents and achieved continuous remission with zero hormones and zero immune agents. She became pregnant six months after CAR-T infusion, and gave birth to a healthy full-term, full-weight baby successfully. She is the first patient in China who successfully discontinued hormone, immune preparations and gave birth after CAR-T therapy. During the follow-up of the patient, we found that the immune indexes had basically returned to normal, and the safety was good. It indicates that CAR-T therapy may represent a promising and innovative therapeutic approach for the management of SLE. This offers hope and establishes a precedent for SLE women of childbearing age.
Female ; Humans ; Pregnancy ; B-Lymphocytes/immunology* ; Immunotherapy, Adoptive/methods* ; Lupus Erythematosus, Systemic/therapy* ; Lupus Nephritis/immunology* ; Receptors, Chimeric Antigen/therapeutic use* ; Young Adult

Objective To study the role of kallikrein 8 (KLK 8) in the pathogenesis of cerebral white matter injury induced by intrauterine infection.Method The pregnant Sprague Dawley rats were randomly assigned into two groups:the observation group and the control group.The rats in the observation group received intraperitoneal injection of lipopolysaccharide (500 μg/kg) by at day 18 and 19 of pregnancy,while the control group received the same dose of saline.The morphology of white matter of the newborn rats were observed at 1 d,3 d,7 d and 14 d after birth.The expression of KLK 8 in the hippocampus was examined using Western blot and reverse transcription-polymerase chain reaction (RTPCR);the concentration of KLK 8 in the serum was measured using enzyme linked immunosorbent assay (ELISA) method at the same time.Result In the observation group,the brain tissue was loose and edematous,the cerebral white matter was weakly stained,and the number of cells reduced.The expressions of KLK 8 in hippocampus in the observation group were higher than the control group [1 d:(0.24 ±0.01) vs.(0.23±0.01),3 d:(0.72±0.02) vs.(0.55±0.04),7 d:(1.08±0.04) vs.(0.84±0.04)],the differences were statistically significant (P ＜ 0.05).The expressions of KLK 8 mRNA in hippocampus of the observation group [1 d:(0.013 ±0.003),3 d:(0.032 ±0.002),7 d:(0.060 ±0.005)] were higher than the control group [1 d:(0.008 ±0.002),3 d:(0.016 ±0.002),7 d:(0.026 ±0.002)],the differences were also statistically significant (P ＜ 0.05).The serum KLK 8 concentration at 1 d,3 d,and 7 d were (5.13 ±0.24) μg/L,(6.46 ±0.24) μg/L,and (7.77 ±0.30) Iμg/L in the observation group,higher than the control group (4.73 ±0.25) μg/L,(5.65 ±0.29) μg/L,and (6.66 ±0.46) μg/L),the differences were also statistically significant (P ＜ 0.05).Conclusion KLK 8 may be involved in the pathogenesis of white matter injury induced by intrauterine infection.

Objective To study the effect of intratumor angiogenesis and vascular growth factor(VEGF), basic fibroblase growth factor(bFGF), Platelet-derived growth factor (PDGF), and their receptors(flt-1 bFGFR.PDGFR) on the invasion, metaslasis of pancreatic carcimoma(PC) and the relationship between the expressions of three kinds of angiogenic factors, their receptors and microvessel count(MVC). Methods Tis- sue sections of 51 PC and 32 acute or chronic pancreatitis were examined by in situ hybridization for the expression of VEGF bFGF.PDGF, and by immunohistochemistry for the expression of the three kinds of angiogenic factor receptors and MVC. The correlation of the expressions and pathological characteristics of PC were also studied. Results The positive rate of VEGF mRNA,bFGF mRNA, PDGF mRNA and their receptors in PC were significantly higher than that in acute or chronic pancreatistis( P