Indroduction SLE is an autoimmune multisystem disease. Glucocorticoid is an irreplaceable medication for SLE. Glucocorticoid and inflammatory mediators impact bone remodeling by OPG/RANKL/RANK signal system, which could lead to osteoporosis. Our aim is to detect the expression of RANKL/OPG in children with SLE, and to preliminarily explore the changes of bone remodeling serum markers in children with SLE. Methods Serum RANKL and OPG of 40 children with SLE and healthy children were detected by ELISA, while 25(OH)VitD3 was detected routinely. Clinical data of children with SLE were recorded, including gender, age, height, weight, BMI, SLEDAI, duration of the disease, cumulative dose of glucocorticoid, and correlation analysis was conducted with RANKL, OPG and 25(OH)VitD3. Results Serum RANKL concentrations in SLE group were significantly higher than health group (9.82 ± 7.20 vs. 6.80 ± 4.35 pg/ml and 0.081 ± 0.072 vs. 0.042 ± 0.034, P < 0.05) respectively, and the concentrations of OPG and 25(OH)VitD3 in serum were significantly lower than health group (156.34 ± 57.33 vs. 189.16 ± 68.70 pg/ml and 43.66 ± 31.27 vs. 59.04 ± 21.56 mmol/L, P < 0.05). Serum RANKL in children with SLE was positively correlated with the duration of SLE, cumulative dose of GC(r = 0.593, 0.727, P < 0.05). And it was negatively correlated with serum OPG and 25(OH)VitD3 (r = -0.601, -0.469, P < 0.05). In addition, serum OPG and 25(OH)VitD3 concentrations were inversely correlated with cumulative dose of GC (r = -0.66, -0.508, P < 0.05). Conclusion Low levels of vitamin D3 and bone metabolic abnormalities still persist in children with SLE even if the disease is in remission, while serum RANKL level was elevated, OPG expression was reduced. In the case of disease remission, GC is involved in the occurrence and development of abnormal bone remodeling through RANKL/OPG.

Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β −/−/CKD, Il6−/−/CKD and Tnfα −/−/CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β −/−/CKD mice but were only partially rescued in Il6−/−/CKD and Tnfα −/−/CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg.kg.day, IP) or saline for 6 weeks and compared with WT/sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.

Objective To explore the clinical characteristics of autoimmune diseases in children with ELANE mutations. Methods Three cases of children with ELANE mutations manifesting as autoimmune diseases, who were under treatment from April 2020 to May 2021, were retrospectively analysed. Results Among the three children, two were boys aged 15 years and 22 months (cases 1 and 3) respectively, and the other one was a 22-month-old girl (case 2). All the cases had recurrent infections. Case 1 presented with cyclic neutropenia and systemic lupus erythematosus (SLE). Case 2 presented with severe neutropenia and autoimmune haemolytic anaemia (AHIA). Case 3 presented with severe neutropenia and anti-neutrophil cytoplasm antibodies (ANCA)-associated small vasculitis. Genetic tests showed that they all had heterozygous mutations in the ELANE gene. Case 1 was treated with methylprednisolone and hydroxychloroquine sulphate for 2 years, making neutrophil level return to normal. Case 2 received allogeneic hematopoietic stem cell transplantation and has stopped taking antibiotics, steroids and all the immunosuppressors. Case 3 received subcutaneous injections of granulocyte colony-stimulating factor, oral prednisone and cyclophosphamide. The boy in case 3 has been followed up for one year, and his absolute neutrophil count has increased to 1.56 × 109/L. Conclusion Patients with ELANE mutations, combined with autoimmune diseases, may have recurrent infections. Disease-modifying antirheumatic drugs (DMARDs) are effective for autoimmune diseases. Autoimmune diseases with ELANE mutations associated with neutropenia can be cured through allogeneic hematopoietic stem cell transplantation.

Objective To explore the clinical characteristics of autoimmune diseases in children with ELANE gene mutation. Methods: Three cases of children with ELANE gene mutation manifested as autoimmune disease were retrospectively analyzed from April 2020 to May 2021. Results: They were 2 males and 1 female, aged 15 years, 1 year and 10 months and 1 year and 10 months, respectively. All of them had recurrent infection. Case 1 presented with cyclic neutropenia and systemic lupus erythematosus. Case 2 presented with severe neutropenia and autoimmune hemolytic anemia. Case 3 presented with severe neutropenia and ANCA-associated small vasculitis. Genetic tests showed that they all had heterozygous mutations in ELANE gene. Case 1 was treated with methylprednisolone and hydroxychloroquine sulfate for 2 years, and had normal neutrophils. Case 2 received allogeneic hematopoietic stem cell transplantation and has stopped taking all drugs. Case 3 received subcutaneous injection of granulocyte colony-stimulating factor, oral prednisone and cyclophosphamide. He has been followed up for one year, and his neutrophils increased to 1.56×109/L. Conclusion Patients with ELANE gene mutation may have recurrent infection, and combined with autoimmune disease. DMARDs are effective for autoimmune disease. Allogeneic hematopoietic stem cell transplantation can cure the disease.

No abstract

Purpose: Exploring efficacy and safety for first single dose of rituximab(RTX) in children with steroid dependent-minimal change nephrotic syndrome(SD-MCNS) by retrospective analysis in two years after RTX and established the model of prediction for relapsing. Methods: Children with SD-MCNS, admitted in our hospital and received single dose of RTX(375mg/m2) by first time from Oct 2011 to Dec 2018, were included. They were followed by 24 months. The clinical and laboratory data before and after RTX were collected and analyzed. Results: 77 patients (M/F: 51/26) were included. The median age was 8.17 years old. The median dependent dosage of steroids was 7.87mg/m2·d. The efficacy for the first single dose of RTX in children with SD-MCNS was 90.91%(70/77), 60 patients (77.9%) for complete remission and 10(13.0%) for partial remission. The relapse rate was 78.3%. There were no severe side effects. Age using RTX, dependent dosage of steroids and CD4+ level before RTX had relationship with efficacy of RTX (B=0.390, -0.091, 0.134, P<0.05). Sex, ageing using RTX, IgE before RTX, WBC and CD3+ when stopping steroids were related to relapsing (B=-1.485, -0.373, 1.278, -0.417, 0.135, P<0.05). The model of prediction for relapsing after RTX in children with SD-MCNS was established.Conclusion: Single dose of RTX is efficiency and safe in children with SD-MCNS, but with high recurrence rate. Patients with older age using RTX, or smaller dependent-dosage of steroids, or higher CD4+ have better efficacy for RTX. Male younger patients with higher IgE relapse more easily.