Objective To investigate the therapeutic effects of interleukin 23p19(IL-23p19) monoclonal antibody in the MRL/lpr lupus-like mouse model. Methods A total of 36 female MRL/lpr mice aged 8 weeks were randomly divided into 6 groups: PBS group (blank control), IgG group (isotype IgG), dexamethasone (DEX) group (positive control), and three IL-23p19 monoclonal antibody treatment groups with different dose gradients: low dose (LD, 1 mg/kg), medium dose (MD, 3 mg/kg), and high dose (HD, 10 mg/kg). Drug intervention began at 12 weeks of age via tail vein injection. Urine protein levels were measured using urine protein test strips; serum anti-dsDNA antibody levels were detected by ELISA; serum creatinine and blood urea nitrogen levels were measured using an automatic biochemical analyzer; renal histopathological changes were analyzed by H&E and PAS staining; immunofluorescence was used to assess IgG and C3 immune complex deposition in kidney tissues; flow cytometry was employed to examine the expression of T helper 1(Th1), Th2, Th17, T follicular helper (Tfh), and regulatory T cells(Treg) cell subsets in the spleen; and RT-qPCR was used to detect the expression of related transcription factors in the spleen. Results IL-23p19 monoclonal antibody reduced urine protein levels, alleviated splenomegaly, improved renal function, and decreased anti-dsDNA antibody levels in MRL/lpr mice. It also mitigated glomerulonephritis and reduced renal immune complex deposition. Furthermore, IL-23p19 monoclonal antibody significantly suppressed the proportion of Th1 and Th17 cells while upregulating Treg cell proportion in the spleen. Additionally, it downregulated T-bet and retinoic acid receptor-related orphan receptor γt (RORγt) mRNA levels and upregulated forkhead box P3(FOXP3) mRNA levels in the spleen. Conclusions IL-23p19 monoclonal antibody demonstrates significant therapeutic effects in MRL/lpr mice, likely through modulation of the Th17/Treg cell balance.
Animals ; Female ; Mice, Inbred MRL lpr ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Antibodies, Monoclonal/therapeutic use* ; Interleukin-23 Subunit p19/immunology* ; Mice ; Lupus Nephritis/drug therapy* ; Kidney/drug effects* ; Antibodies, Antinuclear/blood*

OBJECTIVES: To examine the changes in serum levels of endoplasmic reticulum stress (ERS) proteins GRP78/CHOP in patients with lupus nephritis (LN) and analyze their diagnostic value and association with renal pathological features. METHODS: From a sample bank established based on a multicenter cohort study of systemic lupus erythematosus (SLE), 60 LN patients and 35 SLE patients without renal involvement were randomly selected. ELISA was used to detect serum levels of GRP78 and CHOP in the patients to analyze their correlation with clinical features and their diagnostic ability for LN and active LN. MRL/lpr mice were used as an animal model of LN to examine their serum levels of GRP78 and CHOP expression and renal expressions of endoplasmic reticulum apoptosis-related proteins. RESULTS: Serum GRP78 and CHOP levels were significantly higher in LN patients than in SLE patients without renal involvement (P<0.05), and were also higher in active LN patients than in patients in the stable phase (P<0.05). Correlation analysis indicated that serum GRP78 and CHOP levels were positively correlated with SLEDAI scores and 24-h urinary protein. ROC analysis showed that CHOP had a high diagnostic ability for LN (AUC=0.762) and active LN (AUC=0.933). Consistent with the clinical findings, serum GRP78 and CHOP levels were elevated in LN mice, and the expressions of PERK and IRE1α pathway proteins were also increased in the kidneys of the mice. TUNEL staining showed increased renal cell apoptosis and elevated renal expressions of apoptosis-related proteins in LN mice. CONCLUSIONS Serum levels of GRP78/CHOP are increased in LN patients possibly in association with ERS-induced apoptosis mediated by the PERK/IRE1α dual pathway.
Endoplasmic Reticulum Chaperone BiP ; Lupus Nephritis/blood* ; Transcription Factor CHOP/blood* ; Heat-Shock Proteins/blood* ; Animals ; Apoptosis ; Humans ; Mice ; Mice, Inbred MRL lpr ; Female ; Adult ; Endoribonucleases/metabolism* ; Male ; eIF-2 Kinase/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Young Adult ; Endoplasmic Reticulum Stress ; Kidney/metabolism* ; Middle Aged ; Signal Transduction

OBJECTIVE: A series of common blood tests neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV) could provide a measure of systemic lupus erythematosus (SLE) activity. METHODS: We searched the Medline, Embase, and Cochrane databases and performed a meta-analysis comparing NLR, PLR, and MPV in patients with SLE to controls, and examined correlation coefficients between NLR, PLR, and MPV and SLE activity based on SLE Disease Activity Index (SLEDAI) using random-effects models. RESULTS: Nine studies were included in this meta-analysis. Meta-analysis revealed that NLR was significantly higher in the SLE group than in the control group (standard mean difference [SMD]=2.747, 95% confidence interval [CI]=1.241∼4.254, p<0.001). PLR was also significantly higher in the SLE group (SMD=1.564, 95% CI=0.122∼3.006, p=0.034). Meta-analysis of correlation coefficients showed that both NLR and PLR were positively associated with SLEDAI (correlation coefficient=0.404, 95% CI=0.299∼0.500, p<0.001; correlation coefficient=0.378, 95% CI=0.234∼0.505, p<0.001). The pooled sensitivity and specificity of NLR for diagnosis of lupus nephritis were 75.1% (95% CI, 68.5∼81.0) and 72.9% (95% CI, 64.9∼80.0), respectively. The area under the curve of NLR were 0.794. However, meta-analysis indicated no elevated MPV in the SLE group and no correlation between MPV and SLE activity. CONCLUSION: This meta-analysis demonstrated that both NLR and PLR are higher in patients with SLE, a significantly positive correlation exists between NLR/PLR and SLE activity.
Blood Cell Count ; Blood Platelets* ; Diagnosis ; Hematologic Tests ; Humans ; Lupus Erythematosus, Systemic* ; Lupus Nephritis ; Lymphocytes* ; Mean Platelet Volume* ; Neutrophils* ; Sensitivity and Specificity

PURPOSE: The aim of this study was to assess the clinical characteristics of hypertensive encephalopathy according to the underlying etiologies in children. METHODS: We retrospectively evaluated 33 pediatric patients who were diagnosed as having hypertensive encephalopathy in Chonbuk National University Children's Hospital. Among the patients, 18 were excluded because of incomplete data or because brain magnetic resonance imaging (MRI) was not performed. Finally, 17 patients were enrolled and divided into a renal-origin hypertension group and a non-renal-origin hypertension group according to the underlying cause. We compared the clinical features and brain MRI findings between the 2 groups. RESULTS: The renal group included renal artery stenosis (4), acute poststreptococcal glomerulonephritis (2), lupus nephritis (2), and acute renal failure (1); the nonrenal group included essential hypertension (4), pheochromocytoma (2), thyrotoxicosis (1), and acute promyelocytic leukemia (1). The mean systolic blood pressure of the renal group (172.5±36.9 mmHg) was higher than that of the nonrenal group (137.1±11.1 mmHg, P<0.05). Seizure was the most common neurologic symptom, especially in the renal group (P<0.05). Posterior reversible encephalopathy syndrome (PRES), which is the most typical finding of hypertensive encephalopathy, was found predominantly in the renal group as compared with the nonrenal group (66.6% vs. 12.5%, P<0.05). CONCLUSION: We conclude that the patients with renal-origin hypertension had a more severe clinical course than those with non-renal-origin hypertension. Furthermore, the renal-origin group was highly associated with PRES on brain MRI.
Acute Kidney Injury ; Blood Pressure ; Brain ; Brain Diseases ; Child ; Glomerulonephritis ; Humans ; Hypertension ; Hypertensive Encephalopathy* ; Jeollabuk-do ; Leukemia, Promyelocytic, Acute ; Lupus Nephritis ; Magnetic Resonance Imaging ; Neurologic Manifestations ; Pheochromocytoma ; Posterior Leukoencephalopathy Syndrome ; Renal Artery Obstruction ; Retrospective Studies ; Seizures ; Thyrotoxicosis

To explore the correlation between hyperuricemia and renal damage in patients with lupus nephritis (LN).
 Methods: The data for clinical features, laboratory and renal pathological examination were collected from 177 renal biopsy-proven LN patients with or without hyperuricemia and were retrospectively analyzed to determine the correlation between serum uric acid and renal damage.
 Results: LN patients with hyperuricemia group had higher rate of hypertension and higher level of blood urea nitrogen and serum creatinine while lower estimated glomerular filtration rate (eGFR) and lower positive rate of anti-U1RNP antibody (P<0.05). In the LN patients with hyperuricemia group, renal pathological scores, including acitive index, chronic index and tubulointerstitial lesions, were higher than those in the LN patients without hyperuricemia group (P<0.05). The level of serum uric acid was positively correlated with serum creatinine, renal pathological classification and renal pathological scores while negatively correlated with eGFR (P<0.05).
 Conclusion: LN patients with hyperuricemia are associated with more serious renal damage. Hyperuricemia is an important predictor for poor prognosis in patients with LN.
Blood Urea Nitrogen ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Hypertension ; Hypertension, Renal ; Hyperuricemia ; epidemiology ; Kidney ; pathology ; Lupus Nephritis ; complications ; diagnosis ; Male ; Prognosis ; Retrospective Studies ; Ribonucleoprotein, U1 Small Nuclear ; blood ; Risk Factors ; Uric Acid ; blood

OBJECTIVETo investigate the expression of fractalkine (FKN) in the blood and renal tissues of patients with lupus nephritis and explore its significance.

METHODSAccording to the pathological classification, 48 patients with lupus nephritis were divided into mild group (22 cases) and severe group (26 cases), with 26 healthy subjects as the control group. RT-PCR and enzyme-linked immunosorbent assay were employed to detect the expression of FKN mRNA and protein in the blood of the subjects, and FKN expression and localization in the renal tissue of the patients with lupus nephritis were detected using immunohistochemical staining.

RESULTSThe patients in both the mild and severe groups showed significantly increased expression of blood FKN mRNA and protein compared with the normal controls, and the increase was more obvious in severe cases (P<0.01). In the renal tissues of the patients, FKN was located mainly in the cytoplasm of the glomerular podocytes and renal tubular epithelial, and the number of positive glomerular cells number was significantly greater in severe cases than in the mild cases (P<0.01); FKN expression in the cortical interstitium did not show a significant difference between the 3 groups.

CONCLUSIONFKN expression in the blood and glomeruli of patients with lupus nephritis is related to the severity of renal pathologies.

Adult ; Case-Control Studies ; Chemokine CX3CL1 ; blood ; metabolism ; Female ; Humans ; Kidney ; metabolism ; Lupus Nephritis ; blood ; metabolism ; Middle Aged

Posterior reversible encephalopathy syndrome (PRES) is a neurologic condition characterized by vasogenic edema on neuroimaging and is associated with the setting of severe hypertension, eclampsia, autoimmune disease, malignancy, and immunosuppressive drugs. We report on a 42 year-old female systemic lupus erythematous patient who presented altered consciousness, seizure, and visual disturbance after cyclophosphamide pulse therapy. Magnetic resonance imaging (MRI) showed multi-focal high signal intensity lesions in the parieto-occipital cortex bilaterally and in the subcortical white matter. Her condition was improved and her MRI lesions were resolved after aggressive blood pressure control and high-dose steroid treatment. It is possibly the first reported case of PRES in a patient with lupus, treated with cyclophosphamide pulse therapy during a nephritis flare in Korea.
Autoimmune Diseases ; Blood Pressure ; Consciousness ; Cyclophosphamide ; Eclampsia ; Edema ; Female ; Humans ; Hypertension ; Korea ; Lupus Erythematosus, Systemic ; Lupus Nephritis ; Magnetic Resonance Imaging ; Nephritis ; Neuroimaging ; Pregnancy ; Seizures

OBJECTIVETo analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE).

METHODThe diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria: age ≤ 16 years, number of important organs involved > 1, SLEDAI score > 10 points and poor response to conventional immunosuppressive treatment. These patients received 2 doses of 375 mg/m(2) rituximab (RTX), 2 weeks apart. Clinical, laboratory findings and drug side effects were recorded at RTX initiation, 2 weeks, 1 month, 3, 6 and 12 months after infusion.

RESULTA total of 20 patients. Male to female ratio was 1:3, were enrolled. They were 5-16 years old. The course of disease was (3.0 ± 2.5) years (range: 1 month-7 years), patients were followed up for 12 - 36 months [median: (27.0 ± 7.8) months]. Delirium and cognitive disorders were significantly improved in 10 cases of lupus encephalopathy after 1 month. Lupus nephritis in children were eased slowly, 14/15 patients with lupus nephritis were improved after 2-3 months. Four cases of lupus pneumonia were significantly improved within 1 month. Decreased blood cells counts were relieved at 1 month in 16/18 cases. Cellular immune function was assessed 2 weeks after application of anti-CD20 monoclonal antibody; we found B-cell clearance in 19 patients (95%). B lymphocyte count of 18 patients (90%) was restored within one year. SLEDAI score was reduced obviously. Dose of corticosteroid ranged from (45.0 ± 4.7) mg/m(2) before drug use to (12.0 ± 2.7) mg/m(2) 12 months later (P < 0.001). After the drug use, 5 patients had pneumonia within 6 months; 2 cases who suffered from aspergillus pneumonia and Pneumocystis carinii pneumonia respectively were severe. They accepted mechanical ventilation and anti-inflammatory support after being transferred to the intensive care unit, and their conditions improved at last. No death occurred. In 2 patients the disease recurred with B-cell recovery after 15 months and 18 months. Administration of another cycle of rituximab resulted in remission again in one case but not in the other.

CONCLUSIONAnti-CD20 monoclonal antibody is effective and safe in treatment of severe PSLE. But severe infections may occur in some cases. Focusing on prevention and early treatment can reduce the probability of adverse reactions.

Adolescent ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; adverse effects ; therapeutic use ; B-Lymphocytes ; drug effects ; immunology ; Biomarkers ; blood ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Follow-Up Studies ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Immunologic Factors ; administration & dosage ; adverse effects ; therapeutic use ; Lupus Erythematosus, Systemic ; complications ; drug therapy ; immunology ; Lupus Nephritis ; etiology ; pathology ; Male ; Pneumonia ; etiology ; pathology ; Prednisolone ; administration & dosage ; therapeutic use ; Rituximab ; Severity of Illness Index ; Treatment Outcome

OBJECTIVETo observe the therapeutic effect of total glucosides of paeony (TGP) on lupus nephritis (LN) in MRL/lpr mice.

METHODSMRL/lpr mice with lupus nephritis were randomized into model group and TGP group. The urinary protein content was detected using Coomassie brilliant blue, and the serum levels of IgG anti-double-stranded DNA (dsDNA) antibodies and antinuclear antibodies (ANA) were measured by enzyme-linked immunosorbent assay (ELISA). The changes in the renal pathology were examined microscopically, and the spleen and thymus were weighed to calculate the spleen and thymus indexes.

RESULTSAt 15 and 30 days after TGP administration, the urinary protein content in the TGP group was significantly lower than that in the model group (P<0.05). TGP treatment significantly lowered the serum levels of anti-dsDNA antibodies and ANA and the weight and index of spleen (P<0.05), resulting also in lessened renal pathology at 30 days after the administration. Compared to those before TGP treatment, the urinary protein content and the levels of anti-dsDNA antibodies and ANA decreased significantly at 15 and 30 days after TGP administration (P<0.05), while in the model group, the level of anti-dsDNA increased significantly without obvious changes in urinary protein content or ANA. At 30 days after TGP administration, the urinary protein content was significantly lowered in the TGP group as compared to that at 15 days (P<0.05), but the antibodies showed no significant changes.

CONCLUSIONTGP can reduce urinary protein content and serum levels of anti-dsDNA antibodies and ANA, and lessen renal pathology in MRL/lpr mice with lupus nephritis, suggesting its therapeutic effect on lupus nephritis.

Animals ; Antibodies, Antinuclear ; blood ; Autoantibodies ; blood ; DNA ; immunology ; Female ; Glucosides ; pharmacology ; Lupus Nephritis ; blood ; drug therapy ; urine ; Male ; Mice ; Mice, Inbred MRL lpr ; Paeonia ; chemistry ; Proteinuria ; drug therapy

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown cause. SLE can involve various major organs including heart, lung, kidney, nervous system and bone marrow. Abnormality in immune system producing various autoantibodies is one of the marked features of this disease. Although most diagnostic items primarily depends on clinical symptoms, four of them are the results of laboratory tests; hematologic abnormalities, antinuclear antibody (ANA), immunologic abnormalities and urinalysis. Most patients with SLE have anemia during the disease course. Anemia with chronic disease is the most common in SLE, followed by immune mediated hemolytic anemia and iron deficiency anemia. Fifteen percent of SLE patients have leukopenia and 20% of them have lymphopenia. Leukopenia in SLE is mostly associated with immune mechanism, drugs, bone marrow dysfunction and hyperspenism. Thrombocytopenia in SLE is induced by immune-mediated destruction of platelet, aggregation of platelet in hemolytic anemia, decreased production of platelet by immunosuppressant and concurrent antiphospholipid syndrome. ANA is the most typical blood test in SLE and can be useful screening test. ANA can be also detected in healthy people and patients with other rheumatic and non-rheumatic diseases. Anti-ds DNA Ab and anti-Sm Ab are specific autoantibodies for SLE and are associated clinical manifestations. Anti-ds DNA Ab is well correlated with disease activity of SLE. Lupus nephritis can be classified into six patterns by light microscopy, immunofluorescence and electron microscopy. Class III and IV represent focal and diffuse glomerulonephritis and relatively poor prognosis. Thus patients having these classes of glomerulonephritis need intensive immunosuppressive treatment. The risk of development of lupus nephritis increases in male and younger patients. In SLE patients with end stage renal disease, SLE activity is usually low.
Anemia ; Anemia, Hemolytic ; Anemia, Iron-Deficiency ; Antibodies, Antinuclear ; Antiphospholipid Syndrome ; Autoantibodies ; Autoimmune Diseases ; Blood Platelets ; Bone Marrow ; Chronic Disease ; DNA ; Glomerulonephritis ; Heart ; Hematologic Tests ; Humans ; Immune System ; Kidney ; Kidney Failure, Chronic ; Leukopenia ; Light ; Lung ; Lupus Erythematosus, Systemic ; Lupus Nephritis ; Lymphopenia ; Male ; Mass Screening ; Microscopy, Electron ; Microscopy, Fluorescence ; Nervous System ; Prognosis ; Thrombocytopenia ; Urinalysis