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*

Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged

BACKGROUND: The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. METHODS: Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. RESULTS: In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P  = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P  = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P  = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P  = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P  = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P  = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P  = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P  = 0.002), musculoskeletal damage (P  = 0.023), cardiovascular impairment (P  = 0.009), and CYC use (P  = 0.001); while leukopenia (P  = 0.017), arthritis (P  = 0.014), and mycophenolate usage (P  = 0.013) rates were lower. CONCLUSIONS Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.
Humans ; Female ; Male ; Cross-Sectional Studies ; Sex Characteristics ; East Asian People ; Severity of Illness Index ; Lupus Erythematosus, Systemic/diagnosis* ; Lupus Nephritis/pathology* ; Registries ; Cyclophosphamide/therapeutic use* ; Thrombocytopenia ; Leukopenia/drug therapy* ; Arthritis

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs, and lupus nephritis (LN) is the most common renal complication of SLE. Belimumab is a fully humanized monoclonal antibody that can reduce the number of B cells, thereby reducing the formation of autoantibodies. Belimumab can improve SLE response index and SLE disease activity score and delay the progression of LN in both adults and children and thus plays an important role in the treatment of SLE and LN. This article reviews related research reports of belimumab used in the treatment of children and adults with SLE in China and overseas and analyzes the efficacy and safety of belimumab in pediatric patients, in order to provide a reference for the clinical application of belimumab in children with SLE.
Antibodies, Monoclonal, Humanized ; Child ; Humans ; Immunosuppressive Agents ; Kidney ; Lupus Erythematosus, Systemic/drug therapy* ; Lupus Nephritis ; Treatment Outcome

Lupus-like glomerulonephritis is an immune complex disease with features of lupus nephritis in the absence of systemic lupus erythematosus (SLE). We report a 49-year-old man diagnosed with lupus-like glomerulonephritis associated with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). He was admitted to the hospital for edema. At admission, the serum creatinine was 2.2 mg/dL and the urine protein level was 3.9 mg/day. A renal biopsy showed features of lupus nephritis with no clinical or serological evidence of SLE. Extranodal marginal zone B-cell lymphoma of MALT was discovered concurrently. After successful chemotherapy, the lupus-like glomerulonephritis and lymphoma entered complete remission.
Biopsy ; Creatinine ; Drug Therapy ; Edema ; Glomerulonephritis* ; Humans ; Immune Complex Diseases ; Lupus Erythematosus, Systemic ; Lupus Nephritis ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Middle Aged

OBJECTIVETo observe the therapeutic effect of a drug pair of Radix Astragali and Rehmanniae Radix combined with glucocorticoid (GC) in treating lupus nephritis (LN) patients and its influence on some experimental indices.

METHODSTotally 52 LN patients were randomly assigned to the treatment group (treated by routine Western medicine and a drug pair of Radix Astragali and Rehmanniae Radix, 25 cases) and the control group (treated by Western medicine, mainly by GC and cyclophosphamide, 27 cases). All patients received 6-month therapy. The GC dosage, the withdrawal and reduction dosage of GC, clinical efficacy, systemic lupus erythematosus disease activity index (SLEDAI) score, adverse reactions, and laboratory indicators were recorded.

RESULTS(1) All patients got relieved to some degree with the dosage of GC reduced. The total withdrawal and reduction dosage of GC was slightly higher in the treatment group than in the control group [(50.23 +/- 12.43) mg vs (48.76 +/- 13.61) mg, P > 0.05]. Besides, the prednisone dosage in the treatment group was lower than that in the control group, but without statistical difference (P > 0.05). The ratio of patients in need of adding prednisone for aggravating disease was 24.0%, significantly lower than that in the control group (44.44%, P < 0.05). (2) There was no statistical difference in the SLEDAI score, inflammatory indicators, liver and renal functions, blood electrolytes, blood glucose, blood and urine routines between the two groups (P > 0.05). The 24-h urinary protein count was (1.06 +/- 0.22) g/L in the treatment group, obviously lower than that in the control group (1.43 +/- 0.55 g/L, P < 0.05). (3) There was no statistical difference in the incidence rate of infection, gastrointestinal hemorrhage, psychoneuroses, Cushing's syndrome, cardiovascular anomalies, and femoral head necrosis between the two groups (P > 0.05). But the incidence of adverse reactions such as insomnia, tidal fever, spontaneous sweat, and obesity was less in the treatment group than in the control group (P < 0.05).

CONCLUSIONSUsing a drug pair of Radix Astragali and Rehmanniae Radix combined with GC in treating LN could withdraw the dosage of GC and relieve symptoms it induced. It was advantageous in reducing the dosage of GC and stabilizing patients' conditions.

Adolescent ; Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Lupus Nephritis ; drug therapy ; Treatment Outcome ; Young Adult

BACKGROUNDLupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Although there have been substantial improvements in LN treatment over the last decade, the outcome remains unoptimistic in a considerable percentage of patients. The aim of this study was to evaluate the efficacy and safety of mizoribine (MZR), a novel selective inhibitor of inosine monophosphate dehydrogenase, as induction treatment for active LN in comparison with mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC).

METHODSNinety patients with active LN were observed. Thirty patients were given MZR orally at the dose of 300 mg every other day. Thirty patients took MMF at 2 g per day in two divided doses. Thirty patients received CYC intravenously 0.5 g every 2 weeks. Therapeutic effects and adverse events (AEs) were evaluated at the end of 24-week treatment. One-way analysis of variance (ANOVA) followed by Dunn's test was applied to compare the difference among the groups. For comparing categorical data between two groups, χ(2) test was employed.

RESULTSEarly responses at week 12 were achieved by 73.3%, 90.0%, and 96.7% in MZR, MMF, and CYC groups, respectively. There was no significant difference in the complete remission rates (22.7%, 24.0%, and 25.0%, respectively) or overall response rates (68.2%, 72.0%, and 75.0%, respectively) among the three groups at week 24. The most prominent drop-down of Systemic Lupus Erythematosus Disease Activity Index scores was observed in MMF or CYC group, and the decline of health assessment questionnaire scores in MZR or MMF group was more prominent than that in the CYC group at week 12. Serum complement 3 (C3) or C4 levels were elevated in all groups after the treatments. CYC was more effective in inhibiting anti-double-stranded DNA antibody, while MZR was more effective in inhibiting antinuclear antibody. The incidences of AEs in patients treated with CYC were significantly higher than those in patients treated with MZR or MMF (24.2% for CYC vs. 3.3% for MZR, and 2.6% for MMF, P = 0.01).

CONCLUSIONSMZR is well tolerated and has an effect similar to MMF in the induction therapy of active LN. MZR may serve as an alternative approach for LN patients.

Administration, Intravenous ; Adolescent ; Adult ; Aged ; Cyclophosphamide ; administration & dosage ; therapeutic use ; Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lupus Nephritis ; drug therapy ; Male ; Middle Aged ; Mycophenolic Acid ; administration & dosage ; therapeutic use ; Ribonucleosides ; administration & dosage ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo analyze the clinical and immunological features of children with lupus nephritis (LN).

METHODSChart records of 40 (4 male and 36 female) LN children who were admitted consecutively between January, 2005 and December, 2010 were reviewed. The baseline demographic, pathological and immunological data were analyzed.

RESULTSIn the 40 LN patients analyzed, the mean age of the disease onset was 10.6 ± 2.6 (range from 2.6 to 14.3) years, and 35 cases (88%) were school-age children. Proteinuria was detected in all 40 cases, including nephrotic-range proteinuria in 12 (30%) cases, and isolated proteinuria in 9 (22%) cases. Twenty-six (65%) patients had varying degrees of hematuria. Acute nephritis was the most common sub-type, accounting for 47% of the total cases. Among the 39 cases undergoing renal biopsy, 3 were unclassified and the remaining 36 were classified, respectively, as type IV LN (50%, 18 cases), type II LN (22%, 8 cases). In the histopathologcally classified case, 100% were antinuclear antibody-positive, 61% were anti-dsDNA-positive, and 89% showed varying degrees of decrease in serum C3 and C4 concentrations. Following treatment for 6 months, a high LN remission rate (95%) was achieved; the acute renal activity index remained higher in IV, V+III and V+IV subtypes than in other subtypes, while the chronic index and the degree of tubulointerstitial damage were not different between histopathological subtypes.

CONCLUSIONSThe clinical manifestations of LN children are diverse. Clinically, acute nephritis is the most common form of LN in children. Histopathologically, type IV is the most frequent subtype of LN. Early treatment may result in significant disease remission.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Lupus Nephritis ; drug therapy ; immunology ; pathology ; Male ; Retrospective Studies

Antirheumatic Agents ; administration & dosage ; therapeutic use ; Biological Products ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Evidence-Based Medicine ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lupus Erythematosus, Systemic ; drug therapy ; pathology ; Lupus Nephritis ; drug therapy ; pathology ; Severity of Illness Index

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.
Adult ; Anti-Inflammatory Agents/therapeutic use ; Antirheumatic Agents/therapeutic use ; Antithyroid Agents/*adverse effects/therapeutic use ; Blister/chemically induced/pathology ; Drug Therapy, Combination ; Female ; Graves Disease/diagnosis/drug therapy ; Humans ; Hydroxychloroquine/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Lupus Erythematosus, Systemic/chemically induced/*diagnosis/drug therapy ; Lupus Nephritis/diagnosis/drug therapy ; Methimazole/*adverse effects/therapeutic use ; Mycophenolic Acid/analogs & derivatives/therapeutic use ; Prednisolone/therapeutic use ; Skin/pathology