المؤلفون: Jiayi Lin, Yaqin Zhang, Meihua Wang, Yang Zhang, Pin Li, Yingping Cao, Xuwei Yang

المصدر: Archives of Rheumatology; Jun2022, Vol. 37 Issue 2, p195-204, 10p

مصطلحات موضوعية: METHYLPREDNISOLONE, BIOLOGICAL models, INTERLEUKINS, TERPENES, HETEROCYCLIC compounds, ANIMAL experimentation, PIPERIDINE, JANUS kinases, CELLULAR signal transduction, NEUROTRANSMITTER uptake inhibitors, SYSTEMIC lupus erythematosus, MICE, PHYSIOLOGIC salines

مستخلص: Objectives: This study aims to investigate the effectiveness of tofacitinib, a Janus kinase (JAK) 1/JAK3 inhibitor, in treating murine lupus, and also explore 12 related genes downstream of JAK-signal transducer and activator of transcription (STAT) signaling pathways to find the underlying mechanism. Materials and methods: This study was conducted between July 2017 and January 2020. Fifty-seven female BALB/c mice (aging 8 to 10 weeks old; weighing 18 to 20 g) were assigned to a saline control (SC) group and a pristane-induced lupus group. The latter included four groups, namely, pristane control (PC), tofacitinib (T), methylprednisolone (MP), and tofacitinib plus methylprednisolone (T+MP). Animal models of lupus were induced with pristane, whereas SC mice were treated with normal saline. From the 22nd week after induction, each group was given the aforementioned corresponding intervention for 11 weeks. The following variables were tested: serum concentrations of anti-double-stranded deoxyribonucleic acid (anti-dsDNA), interleukin 6 (IL-6), and interferon gamma (IFN-γ); number of regulatory T (Treg) cells; messenger ribonucleic acid levels of forkhead box P3 and 12 related genes downstream of JAK-STAT pathway; and renal impairment. Results: Red swollen joints and proteinuria were first observed in PC after the 12th week. After treatment, T, MP, and T+MP showed relieved red swollen joints and splenomegaly, as well as decreased urine protein, anti-dsDNA, IL-6, IFN-γ, Treg cells, pathological scores, and hyperplasia of mesangial matrix in glomeruli compared with PC. The IFN regulatory factor 7 level was higher in T+MP (p<0.01) and slightly higher in T (p>0.05) and MP (p>0.05) than in PC after treatment. The expression of suppressor of cytokine signaling (SOCS) 1 was lower in T (p>0.05), T+MP (p<0.01), and MP (p>0.05) than in PC. The SOCS3 level was higher in T (p>0.05) and T+MP (p<0.01) and lower in MP (p>0.05) than in PC. Conclusion: Tofacitinib can ameliorate glomerulonephritis and arthritis in a pristane-induced murine model of lupus. SOCS3 gene may be involved in the therapeutic mechanism of tofacitinib. [ABSTRACT FROM AUTHOR]

: Copyright of Archives of Rheumatology is the property of Turkish League Against Rheumatism / Turkiye Romatizma Arastirma ve Savas Dernegi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Xiangfang CHEN, Wenzhong QUE, Xiangxiong ZHENG, Shiwen ZOU, Pin LI, Xuwei YANG

المصدر: Archives of Rheumatology; Mar2019, Vol. 34 Issue 1, p88-95, 8p, 3 Charts

مصطلحات موضوعية: PULMONARY hypertension, ARTHRITIS, AUTOANTIBODIES, BIOMARKERS, BLOOD sedimentation, C-reactive protein, DYSPNEA, ECHOCARDIOGRAPHY, EPILEPSY, IMMUNOGLOBULINS, PEPTIDE hormones, PROTEINURIA, RAYNAUD'S disease, RISK assessment, SYSTEMIC lupus erythematosus, COMORBIDITY, LOGISTIC regression analysis, DISEASE duration, EARLY diagnosis, DESCRIPTIVE statistics, HYPERTENSION risk factors

مصطلحات جغرافية: CHINA

مستخلص: Objectives: This study aims to evaluate the systemic lupus erythematosus (SLE) frequency, clinical characteristics, and laboratory features of pulmonary hypertension (PH) in a Chinese population with SLE and to evaluate the risk factors contributing in early diagnosis. Patients and methods: A total of 39 patients (2 males, 37 females; mean age 38.2±14.9 years; range, 16 to 71 years) with combined SLE and PH and 407 patients (43 males, 364 females; mean age 34.8±14.0 years; range, 7 to 73 years) with SLE but without PH (NonPH) were enrolled and categorized into two groups, namely, PH and NonPH groups. The demographic and clinical characteristics of all patients, including disease duration, comorbidity, malar rash, epilepsy, arthritis, oral ulcer, photosensitivity, Raynaud's phenomenon, serositis, dyspnea, and visceral damage, were recorded. Laboratory parameters, including blood and urine routine, biochemical markers, 24-hour proteinuria, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), immunoglobulin, complement 3 and 4, and autoantibodies, were tested. Inflammatory indexes, such as erythrocyte sedimentation rate and C-reactive protein level, were collected. Disease activity was assessed with systemic lupus erythematosus disease activity index score. Organ damage was assessed with the use of Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SLICC/ACR-DI; SDI). Pulmonary arterial systolic pressure was measured using echocardiography. Results: Pulmonary hypertension frequency in our Chinese population with SLE was 8.74%. Statistical differences in neuropsychological symptoms, epilepsy, serositis, Raynaud's phenomenon, tachypnea, albumin, creatinine, abnormal electrocardiograph, urine protein, urine red blood cell rate, NT-proBNP, body mass index, SDI and duration of SLE were found between SLE patients with or without PH. Multivariate logistic regression revealed that Raynaud's phenomenon, serositis, tachypnea, epilepsy, and positive anti-U1 small nuclear ribonucleoprotein (U1RNP) were significant risk factors for PH in SLE. Conclusion: Chinese patients with SLE are at high risk for PH if they present with epilepsy, Raynaud's phenomenon, serositis, tachypnea, and positive anti-U1RNP. Echocardiography is highly recommended to be performed on Chinese patients with SLE for the screening of PH. [ABSTRACT FROM AUTHOR]

: Copyright of Archives of Rheumatology is the property of Turkish League Against Rheumatism / Turkiye Romatizma Arastirma ve Savas Dernegi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)