The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic ADs, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics. Despite the initial success achieved by CAR T cell therapy, it is critical to acknowledge the divergences in its application between cancer and ADs. Through examining recent clinical studies and ongoing research, we highlight the transformative potential of this therapeutic approach in the treatment of SLE, while also addressing the challenges and future directions necessary to enhance the long-term efficacy and safety of CAR-based cell therapies in clinical practice.
Humans ; Lupus Erythematosus, Systemic/immunology* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; Cell- and Tissue-Based Therapy/methods* ; Animals ; T-Lymphocytes/immunology*

Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

OBJECTIVETo investigate the effect of Lang-chuang-ding Decoction (, LCD) on the expression of DNA methylation of CD70 gene promoter in peripheral blood mononuclear cells (PBMCs) of females with systemic lupus erythematosus (SLE).

METHODSPBMCs isolated from female patients with SLE or healthy donors were cultured and treated with LCD medicated serum or normal serum for 24 or 48 h. The mRNA expressions of CD70 gene in PBMCs were detected by reverse transcription polymerase chain reaction (PCR); the DNA methylation of the CD70 gene promoter region was detected by methylation-specific PCR.

RESULTSAfter treated with medicated serum for 48 h, the mRNA expression levels of CD70 in PBMCs of SLE patients were signifificantly higher than those of healthy donors (P<0.05); the DNA methylation levels of CD70 promoter region in PBMCs of SLE patients treated with medicated serum for 48 h were signifificantly higher than those treated with fetal bovine serum (P<0.01).

CONCLUSIONLCD could inhibit CD70 gene expression in PBMCs of SLE patients by promoting the DNA methylation of CD70 gene promoter.

Adult ; CD27 Ligand ; genetics ; metabolism ; DNA Methylation ; drug effects ; genetics ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression Regulation ; drug effects ; Humans ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Lupus Erythematosus, Systemic ; drug therapy ; genetics ; Promoter Regions, Genetic ; RNA, Messenger ; genetics ; metabolism

BACKGROUND/AIMS: Protein-losing enteropathy (PLE), characterized by severe hypoalbuminemia and peripheral edema, is a rare manifestation of systemic lupus erythematosus. This present study aimed to identify the distinctive features of lupus-related PLE and evaluate the factors related to the treatment response. METHODS: From March 1998 to March 2014, the clinical data of 14 patients with lupus PLE and seven patients with idiopathic PLE from a tertiary center were reviewed. PLE was defined as a demonstration of protein leakage from the gastrointestinal tract by either technetium 99m-labelled human albumin scanning or fecal alpha1-antitrypsin clearance. A positive steroid response was defined as a return of serum albumin to > or = 3.0 g/dL within 4 weeks after initial steroid monotherapy, and remission as maintenance of serum albumin > or = 3.0 g/dL for at least 3 months. A high serum total cholesterol level was defined as a level of > or = 240 mg/dL. RESULTS: The mean age of the lupus-related PLE patients was 37.0 years, and the mean follow-up duration was 55.8 months. Significantly higher erythrocyte sedimentation rate and serum total cholesterol levels were found for lupus PLE than for idiopathic PLE. Among the 14 patients with lupus PLE, eight experienced a positive steroid response, and the serum total cholesterol level was significantly higher in the positive steroid response group. A positive steroid response was associated with an initial high serum total cholesterol level and achievement of remission within 6 months. CONCLUSIONS: In lupus-related PLE, a high serum total cholesterol level could be a predictive factor for the initial steroid response, indicating a good response to steroid therapy alone.
Adult ; Aged ; Biomarkers/blood ; Cholesterol/blood ; Drug Therapy, Combination ; Edema/diagnosis/drug therapy/*etiology ; Female ; Glucocorticoids/therapeutic use ; Humans ; Hypoalbuminemia/diagnosis/drug therapy/*etiology ; Immunosuppressive Agents/therapeutic use ; Lupus Erythematosus, Systemic/*complications/diagnosis/drug therapy ; Male ; Middle Aged ; Protein-Losing Enteropathies/diagnosis/drug therapy/*etiology ; Remission Induction ; Risk Factors ; Serum Albumin/metabolism ; Tertiary Care Centers ; Time Factors ; Treatment Outcome

OBJECTIVETo observe the effects of Xuebijing injection on dendritic cells (DCs) and T lymphocytes, and the potential mechanisms of its therapeutic effect on systemic lupus erythematosus (SLE).

METHODSA widely used mouse model, SLE-prone BLLF1 mice aged 8-10 weeks, was employed. Mice were randomly divided into 4 groups: a normal group, a model group and two treatment groups treated with Xuebijing Injection with a dose of 6.4 mL/kg via intraperitoneal administration for SLE-prone BLLF1 mice aged 8 weeks (treatment A group) and 10 weeks (treatment B group). Renal tissue sections were stained with Masson's trichrome and periodic acid-silver methenamine. Histopathological changes in the kidney were evaluated by a light microscopy. The capacity of the DCs isolated from the spleen to stimulate the T cell proliferation in response to concanavalin A (Con A) was determined.

RESULTSCompared with the model group, levels of anti-dsDNA antibodies in the two treatment groups decreased remarkablly (P<0.01, P<0.05), and levels of serum creatinine and blood urea nitrogen increased (P<0.01, P<0.05). Pathological changes were found in the kidney in the model group. Histopathological abnormalities were alleviated in the two treatment groups. Treatment with Xuebijing injection also significantly upregulated the expression of CD80, CD86 and major histocompatibility class II by DCs compared with the model group (P<0.05). When splenic T lymphocytes from BLLF1 mice were co-cultured with DCs at ratios of 1:100, 1:150 and 1:200 for 3 and 5 days, the proliferation of T lymphocytes was suppressed compared with the normal group (P<0.05), but this was restored by Xuebijing Injection under the same conditions. In the model group, levels of tumor necrosis factor (TNF)-α in supernatants were significantly elevated compared with the normal group (P<0.01), interleukin-2 levels decreased (P<0.05), while these changes were significantly alleviated in the Xuebijing treatment groups.

CONCLUSIONSXuebijing Injection alleviated renal injury in SLE-prone BLLF-1 mice. The mechanism might be through influencing T cell polarization mediated by DCs, and Xuebijing Injection might be a potential drug that suppresses immune dysfunction in patients with SLE.

Animals ; Antibodies, Antinuclear ; blood ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Concanavalin A ; pharmacology ; Dendritic Cells ; drug effects ; immunology ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Injections ; Interleukin-2 ; metabolism ; Kidney ; drug effects ; pathology ; physiopathology ; ultrastructure ; Kidney Function Tests ; Lupus Erythematosus, Systemic ; blood ; drug therapy ; immunology ; physiopathology ; Mice ; Phenotype ; T-Lymphocytes ; drug effects ; immunology ; pathology ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUND: We assessed the efficacy of serial interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in patients receiving immunosuppressive agents for treatment of rheumatic diseases in Korea. METHODS: Of 276 patients who underwent consecutive screening with one of two IGRAs [QuantiFERON-TB Gold or QuantiFERON-TB Gold In-Tube], 66 patients were evaluated by the serial IGRA for detection of LTBI during therapy with immunosuppressive agents. Information on clinical diagnosis, medication, previous TB, blood cell count, tuberculin skin test, and interferon-gamma (IFN-gamma) level measured by IGRA was collected. RESULTS: Of the 66 patients, the initial IGRA was positive in 24.2%, negative in 65.2%, and indeterminate in 10.6%. Forty-six patients (69.7%) showed consistent IGRA results during follow-up, and 13 patients (19.7%) had consistently positive results. IGRA conversion rate was 12.1% (8/66) and reversion rate was 4.5% (3/66). Conversion of IGRA results was only observed in ankylosing spondylitis patients, and the median interval between the two tests in patients with conversion was 8.5 months. The mean IFN-gamma level in the group of patients with consistently positive IGRA results was higher than that in the group with inconsistently positive results, although this trend was not statistically significant (P=0.293). Indeterminate results were observed most frequently in patients with systemic lupus erythematosus. CONCLUSIONS: In patients receiving immunosuppressive agents, both IGRA conversions and reversions were observed. Serial IGRA testing may not be needed in patients with a positive initial IGRA result showing high IFN-gamma levels, because of high consistency in the test results.
Adult ; Blood Cell Count ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents/*therapeutic use ; Interferon-gamma/*analysis ; *Interferon-gamma Release Tests ; Latent Tuberculosis/complications/*diagnosis/metabolism ; Lupus Erythematosus, Systemic/complications/diagnosis/metabolism ; Male ; Middle Aged ; Rheumatic Diseases/complications/diagnosis/drug therapy ; Spondylitis, Ankylosing/complications/diagnosis/metabolism ; Tuberculin Test

Candidiasis ; drug therapy ; immunology ; metabolism ; Diabetes Mellitus, Type 1 ; complications ; drug therapy ; immunology ; therapy ; Humans ; Lupus Erythematosus, Systemic ; drug therapy ; immunology ; metabolism ; Mycoses ; complications ; immunology ; therapy ; Paraneoplastic Syndromes ; drug therapy ; immunology ; metabolism ; Pemphigus ; drug therapy ; immunology ; metabolism

OBJECTIVETo explore the mRNA expressions of IL-10, IL-18 and Fas in peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients of various Chinese medicine syndrome types in order to seek the objective indices for syndrome differentiation of SLE.

METHODSSLE patients were sorted into various syndrome types by Chinese medicine syndrome differentiation. In them, patients with the 4 often encountered types were selected, i.e. the qi-xue excessive heat type (Group A, 12 patients), the Pi-Shen yang-deficiency type (Group B, 19 patients), the qi-yin deficiency with blood stasis type (Group C, 23 patients), and the qi stagnation and blood stasis with gan stagnation type (Group D, 28 patients). The mRNA expressions of IL-10, IL-18 and Fas in PBMCs were detected by SYBR Green I real time PCR.

RESULTSThe mRNA expressions of IL-10, IL-18 and Fas in PBMC of all SLE patients (0.40 +/- 0.53, 1.41 +/- 1.93 and 0.33 +/- 0.70) were significantly higher than those in the normal control group (0.07 +/- 0.11, 0.24 +/- 0.25, 0.08 +/- 0.21, P<0.01, P<0.05), their levels in different syndrome types decreased in order of type A-->B-->C-->D. The levels of the three indices in patients of type A and B were obviously higher than those in patients of type C and D (P<0.01), while no significant difference was found between type A and B (P>0.05), and between type C and D (P>0.05).

CONCLUSIONThe mRNA expressions of IL-10, IL-18 and Fas in PBMCs could be taken as the objective indices for reference in syndrome differentiation of SLE.

Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; blood ; diagnosis ; therapy ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; RNA, Messenger ; genetics ; Yang Deficiency ; diagnosis ; Yin Deficiency ; diagnosis ; Young Adult ; fas Receptor ; blood

OBJECTIVETo investigate the effect of arsenic trioxide (ATO) on the autoimmunity and survival time in BXSB lupus mice.

METHODSThe model BXSB lupus mice were randomly divided into two groups equally, the ATO treated group and the control group, 17 in each group. Mice in the ATO group were given intraperitoneal injection of ATO at the daily dose of 0.4 mg/kg, once every other day for 105 days or 90 days, respectively, and the observation lasted for 210 days. The survival time between the two groups was compared; the serum levels of anti-dsDNA and IgG were detected by enzyme-linked immunosorbent assay (ELISA), and the interferon-gamma (IFN-gamma) mRNA expression in renal and spleen tissue were measured by reverse transcriptase polymerase chain reaction (RT-PCR) technique.

RESULTSTill the 210th day, the total number of death was 8 in the ATO treated group and 13 in the control group, comparison between the two groups showed significantly different (chi2 = 4.20, P < 0.05). The mean OD value of serum anti-dsDNA antibody was lower in the ATO group (0.392 +/- 0.087) than that in the control group (0.566 +/- 0.080, P < 0.001). The serum level of IgG on day 105 in the ATO group was significantly lower than that in the control group and before treatment (P < 0.05). The expression of IFN-gamma mRNA in spleen tissue and renal tissue in the ATO group and the control group was 0.540 +/- 0.300 and 0.338 +/- 0.163, 2.320 +/- 0.522 and 0.588 +/- 0.104 (P < 0.05 and P < 0.01 respectively).

CONCLUSIONATO can prolong the survival time of BXSB lupus mice, decrease the peripheral level of anti-dsDNA antibody and IgG expression, inhibit the over-expression of IFN-gamma mRNA in spleen and kidney tissues.

Animals ; Antibodies, Antinuclear ; blood ; Arsenicals ; administration & dosage ; therapeutic use ; Autoimmunity ; drug effects ; Enzyme-Linked Immunosorbent Assay ; Immunoglobulin G ; blood ; Injections, Intraperitoneal ; Interferon-gamma ; genetics ; Kidney ; drug effects ; metabolism ; Lupus Erythematosus, Systemic ; drug therapy ; genetics ; immunology ; Mice ; Oxides ; administration & dosage ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Spleen ; drug effects ; metabolism ; Survival Analysis

OBJECTIVETo observe the therapeutic efficacy and safety of Haoqin Qingdan Decoction (HQD) in treating active stage of systemic lupus erythematosus (SLE).

METHODSOne hundred and twenty patients with SLE were randomly assigned into two groups, the treated group receiving HQD and prednisone, and the control group receiving prednisone and cyclophosphamide (CTX), both were treated for 3 months. SLE disease activity index (SLEDAI), various immunological indexes, blood and urine routine, hepatic and renal function, as well as the other adverse reaction of the treatment were observed.

RESULTSThe total effective rate in the treated group was 81.67% (49/60), while 76.67% (46/60) in the control group, showing insignificant difference between the two groups. SLEDAI, erythrocyte sedimentation rate (ESR), complement 3 (C3), 24-hr urinary protein excretion and anti-double strain deoxyribonucleic acid (dsDNA) antibody were improved in the treated group, and no obvious adverse reaction was shown.

CONCLUSIONHQD is obviously more effective in treating active stage of SLE with high safety.

Adolescent ; Adult ; Aged ; Complement C3 ; metabolism ; Drug Administration Schedule ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Lupus Erythematosus, Systemic ; drug therapy ; Male ; Middle Aged ; Phytotherapy ; Prednisone ; administration & dosage