Spondyloenchondrodysplasia with immune dysregulation caused by ACP5 gene mutation: a case report and literature review / 中华实用儿科临床杂志

Objective:To summarize the clinical features and gene phenotype of children with spondyloenchondrodysplasia with immune dysregulation (SPENCDI) caused by ACP5 gene mutation. Methods:The medical data and genetic phenotype of a child diagnosed with SPENCDI in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University in February 23, 2017 were analyzed retrospectively.Besides, " spondyloenchondrodysplasia" were taken as the search terms to perform the retrieval in CNKI, Wanfang Data, and PubMed, in an attempt to conduct the literature review.χ 2 test was used to compare the factors among children with different mutations. Results:The 4.5-year-old girl was admitted to hospital for complaint of " fever and chilblain-like rash" when she was 2 years old.She was diagnosed with systemic lupus erythematosus (SLE) concomitant with lupus nephritis.Methylprednisolone combined with cyclophosphamide, mycophenolate mofetil was used for the treatment.However, she experienced multiple infections, thrombocytopenia, limp, and growth retardation during the treatment.Genetic detection identified ACP5 gene compound hybrid mutation: c.779C>A and c. 770T>C.She was diagnosed with SPENCDI, and was subjected to follow-up.A total of 78 SPENCDI patients were retrieved from the databases, with various clinical manifestations of SPENCDI, commonly with skeletal involvement and immune phenotypes; 73.08% of the cases were positive for antinuclear antibodies, 57.69% of cases were positive for anti-double stranded-DNA antibodies and 34.62% of cases had neurological symptoms.In 58 cases, ACP5 gene mutations were detected, including 44 homozygous mutations and 14 compound heterozygous mutations.Patients with ACP5 gene homozygous mutation had a higher probability of consanguineous marriage in parents [56.82% (25/44 cases) vs.14.29% (2/14 cases)]; patients with ACP5 gene heterozygous mutation were more likely to develop SLE [64.29% (9/14 cases) vs.34.09% (15/44 cases)]( χ2=7.722, 3.992; all P<0.05). Conclusions:The majority of the ACP5 gene mutations are homozygous mutations in patients with SPENCDI, and heterozygous mutations are rare.The clinical manifestations of SPENCDI are various and complex, it is prone to develop autoimmune diseases, and there was no clear correlation between clinical features and gene phenotype in SPENCDI patients.

Clinical Relevance of Autoantibodies against Interleukin-2 in Patients with Systemic Lupus Erythematosus / 中华医学杂志(英文版)

<p><b>Background</b>Increased serum autoantibodies against interleukin-2 (anti-IL-2 autoantibodies) were reported in patients with systemic lupus erythematosus (SLE) and in patients receiving IL-2 therapy. This study aimed to explore the clinical relevance of serum anti-IL-2 autoantibodies and the interactions between low-dose IL-2 therapy and serum anti-IL-2 autoantibodies.</p><p><b>Methods</b>Serum samples were collected from 152 SLE patients and 100 age- and gender-matched healthy controls (HCs). Among them, 75 SLE patients were followed up for 10 weeks, and all of them were treated with corticosteroids, antimalarials, and/or immunosuppressants. Forty-six out of the 75 SLE patients received low-dose IL-2 therapy additionally. Clinical and laboratory parameters were collected at baseline and week 10. Serum anti-IL-2 autoantibodies were determined by enzyme-linked immunosorbent assay.</p><p><b>Results</b>Compared with HCs, median levels and positive rates of serum anti-IL-2 autoantibodies were higher in SLE patients (32.58 [23.63, 45.23] arbitrary unit [AU] vs. 37.54 [27.88, 60.74] AU, P = 0.006, and 5.0% vs. 18.4%, P = 0.002, respectively). Compared to those without the corresponding disorders, serum anti-IL-2 autoantibody was increased in patients with alopecia (49.79 [36.06, 64.95] AU vs. 35.06 [25.40, 58.46] AU, P = 0.033), but it was decreased in those with lupus nephritis (31.71 [22.60, 43.25] AU vs. 44.15 [31.43, 68.52] AU, P = 0.001). Moreover, serum anti-IL-2 autoantibody was positively correlated with serum IgA (r = 0.229, P = 0.005), total IgG (r = 0.327, P < 0.001), and total IgM (r = 0.164, P = 0.050). Treatment with exogenous IL-2 was not significantly associated with serum anti-IL-2 autoantibody. In addition, no significant difference was found in serum anti-IL-2 autoantibody between responders and nonresponders to low-dose IL-2 therapy.</p><p><b>Conclusions</b>Serum anti-IL-2 autoantibody was increased and associated with disease severity in SLE. Exogenous low-dose IL-2 did not significantly induce anti-IL-2 autoantibody production.</p>

Effect of HMG-CoA Reductase Inhibitor Drugs (Statins) on Systemic Lupus Erythematosus Disease Activity: A systematic review and meta-analysis

Introduction@#Statins have been shown to have antiinflammatory and immunomodulatory effects. In vitro studies show that these drugs inhibit inflammatory cells, decrease the expression of major histocompatibility complex (MHC), decrease adhesion molecules and inflammatory cytokines (IL6 and IL10), that are also implicated in SLE pathogenesis. In terms of immunomodulary effects, animal studies demonstrate that statins exacerbate/trigger cellular apoptosis and induce a shift in the Th1/Th2 balance leading to B-cell reactivity and production of pathogenic autoantibodies. Whether statins have clinical effects in SLE have not been widely studied. In terms of disease activity, studies show contradicting results. The researchers aim to determine the effect of statins on the disease activity of SLE based on the best available evidence@*Methods@#A systematic literature search of PubMed, Scopus, and Cochrane databases was done with no date and language restrictions. Included studies were on adult SLE patients and randomized controlled trials that used statins as intervention and reported SLE disease activity as an outcome measure. Two reviewers did quality appraisal, risk bias assessment, and data extraction.@*Results@#Three studies met the eligibility criteria and were included in this review. Quantitative synthesis was done. The pooled analysis of these studies suggests that atorvastatin has no significant effect on disease activity using random effects model with an overall effect of 0.12 (P=0.90, 95% CI -1.65, 1.88).@*Conclusion@#Atorvastatin neither increased nor decreased SLE disease activity. Therefore possibly it can be safely given to SLE patients without the risk of triggering or exacerbating a flare.

Hyperuricemia in systemic lupus erythematosus: is it associated with the neuropsychiatric manifestations of the disease? / Hiperuricemia no lúpus eritematoso sistêmico: está associada a manifestações neuropsiquiátricas da doença?

ABSTRACT Objectives: To assess the association between hyperuricemia and different neuropsychiatric manifestations and stroke risk factors in systematic lupus erythematosus (SLE) patients. Methods: This study was conducted on 204 SLE patients who were admitted to a tertiary referral center. A standardized questionnaire was completed for all the participants and the medical records were reviewed regarding the occurrence of arterial or venous thrombotic events, stroke, seizure, depression, headache, psychosis, and peripheral neuropathy. In addition blood samples were drawn to obtain serum uric acid, triglyceride (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol levels. Results: Hyperuricemia (serum uric acid ≥6 mg/dl for women and ≥7 mg/dl for men) was detected in 16.1% of SLE patients and was significantly associated with the occurrence of stroke (OR, 2.38; 95%CI, 1.2-7.24), and peripheral neuropathy (OR, 3.49; 95% CI, 1.52-12.23), independent of hypertension and hyperlipidemia. Hyperuricemia was also significantly associated with hypertension (OR, 7.76; 95% CI, 2.72-15.76), hyperlipidemia (OR, 5.05; 95% CI, 1.59-11.32), and history of arterial thrombosis (OR, 4.95; 95% CI, 1.98-15.34), independent of age and body mass index. Conclusions: Hyperuricemia in SLE patients is independently associated with the occurrence of stroke and peripheral neuropathy. It is also independently associated with hypertension, hyperlipidemia, and history of arterial thrombosis, which are the major stroke and myocardial infarction risk factors in SLE patients.

RESUMO Objetivos: Avaliar a associação entre a hiperuricemia e diferentes manifestações neuropsiquiátricas e os fatores de risco para AVE em pacientes com lúpus eritematoso sistêmico (LES). Métodos: Este estudo foi feito em 204 pacientes com LES que foram internados em um centro de referência de atenção terciária. Todos os participantes preencheram um questionário padronizado e os prontuários médicos foram analisados quanto à ocorrência de eventos trombóticos arteriais ou venosos, acidente vascular encefálico, convulsão, depressão, cefaleia, psicose e neuropatia periférica. Além disso, foram coletadas amostras de sangue para se mensurarem os níveis de ácido úrico, triglicerídeos (TG), lipoproteínas de alta densidade (HDL), lipoproteínas de baixa densidade (LDL) e colesterol total do sangue. Resultados: A hiperuricemia (ácido úrico sérico ≥ 6 mg/dL para mulheres e ≥ 7 mg/dL para homens) foi detectada em 16,1% dos pacientes com LES e esteve significativamente associada à ocorrência de AVE (OR, 2,38; IC 95%, 1,2-7,24) e neuropatia periférica (OR, 3,49; IC 95%, 1,52-12,23), independentemente da hipertensão arterial e da hiperlipidemia. A hiperuricemia também esteve significativamente associada à hipertensão arterial (OR, 7,76; IC 95%, 2,72-15,76), hiperlipidemia (OR, 5,05; IC 95%, 1,59-11,32) e história de trombose arterial (OR, 4,95; 95% CI, 1,98-15,34), independentemente da idade e do índice de massa corporal. Conclusões: A hiperuricemia em pacientes com LES está independentemente associada à ocorrência de acidente vascular encefálico e neuropatia periférica. Também está independentemente associada à hipertensão, hiperlipidemia e história de trombose arterial, que são os principais fatores de risco para acidente vascular encefálico e infarto agudo do miocárdio em pacientes com LES.

Mechanism Study on Nano-Realgar Intervention of TWEAK-NF-κB Signal Pathway through Downregulation of Chemokines in Kidney Expression among MRL/lpr Mice / 世界科学技术-中医药现代化

This study was aimed to explore the molecular mechanism of nano-realgar in treatment of systematic lupus erythematosus (SLE) lupus nephritis (LN). Intragastric administration of equal volume of high-, middle-, low-dose nano-realgar suspension, and normal saline (NS) were given to MRL/lpr mice, respectively. The observations were made on levels of ANA, ds-DNA antibody, IgG and IgM in blood serum, as well as TWEAK, NF-κB, MCP-1 mRNA and protein expression levels in renal tissues. The results showed that compared with the NS group, levels of ANA, ds-DNA antibody, IgG and IgM were obviously reduced (P < 0.05); the levels of TWEAK, NF-κB and MCP-1 mRNA were obviously reduced (P < 0.05); the protein expression levels of TWEAK, NF-κB and MCP-1 mRNA were obviously reduced (P < 0.05) in the high-, middle-, low-dose nano-realgar group. It was concluded that nano-realgar intervened the TWEAK-NF-κB signal pathway through downregulating MCP-1 expression among MRL/lpr mice, in order to reduce the levels of ANA, ds-DNA antibody, IgG and IgM for relieving autoimmune damages in the treatment of SLE (LN).

Effects of Blood-cooling and Blood-stasis-removing Decoction on Autoantibody and Serum Levels of Interleukins 6, 17, 21 in MRL/lpr Experimental Rats / 广州中医药大学学报

Objective To observe the effect of blood-cooling and blood-stasis-removing Decoction on anti-double-strain DNA ( anti-dsDNA) antibody, anti-nucleosome antibody ( AnuA) and serum levels of interleukin ( IL) -6, 17, 21 in spontaneous systemic lupus erythematosus ( SLE) MRL/lpr experimental rats. Methods The experimental rats were divided into blank control group, model group, and high- and low- dose Chinese medicine groups ( 25.2, 12.6 g/kg respectively) , the treatment lasting 8 weeks. At the end of the experiment, the blood taken from the orbital veins was separated for obtaining serum, and then the serum anti-dsDNA antibody, AnuA, IL-6,17,21 levels were tested by enzyme-linked immunosorbent assay ( ELISA). Results The serum autoantibody and IL-6, 17, 21 levels of rats in the model group were increased significantly as compared with the blank control group ( P<0.01). The serum antibody and cytokine levels of Chinese medicine groups were reduced as compared with the model group, the difference between high-dose Chinese medicine group and model group being significant ( P<0.01). Conclusion Blood-cooling and blood-stasis-removing Decoction has certain effect on reducing the serum levels of anti-dsDNA antibody, AnuA, and IL-6,17,21, which may coniribute to one of its therapeutic mechanisms for SLE.

Factores de riesgo convencionales, no convencionales y lúpicos para ateroesclerosis en pacientes con lupus eritematoso sistémico / Conventional risk factors, unconventional and lupus for atherosclerosis in patients with systemic lupus erythematosus

El lupus eritematoso es un desorden inmune multisistémico e inflamatorio crónico que esta asociado con el desarrollo prematuro y severo de ateroesclerosis permitiendo de este modo colocar a las enfermedades cardiovasculares como la principal causa de morbi-morbilidad en pacientes con dicha enfermedad. La presente investigación se propuso, evaluar los factores de riesgo convencionales, no convencionales y lúpicos en pacientes con lupus eritematoso sistematico que contribuyen al desarrollo de ateroesclerosis. Para ello, a los pacientes (femenino n=14 y masculino n=1) se le realizaron las siguientes determinaciones: índice de masa corporal (IMC), circunferencia abdominal (CA), perfil lipídico (colesterol, HDL-c, LDL-c, VLDLc y triglicéridos), ácido úrico, velocidad sedimentación globular (VSG) y fibrinógeno. Donde se encontró, 85,71% (12/15) y 100% (14/15) de las pacientes padecían obesidad, ya que presentaron valores elevados del IMC (38,20±5,30 kg/mm2) y de CA(92,32±7,25 cm), respectivamente; 100% (15/15) baja concentraciones sérica de HDL-c (26,00±13,03 mg/dL); 93,33% (14/15) mostraron un estilo de vida sedentario; 33,33% (5/15) eran hipertensos diagnosticados y con tratamiento hipotensor, 33,33% (5/15) presentaban antecedentes familiares de enfermedad cardiovascular 6,66% (1/ 15) niveles elevados de VLDL-c; 6,66% (1/15) hipertrigliceridemia. También se encontró que 20% (3/15) presentaron hiperfibrinogenemia (434,50±38,90 mg/dL), 26,66% (4/15) hiperuricemia (10,46±2,45 mg/dL) y 100% presentó valores por encima del rango de referencia para la VSG. Estos resultados sugieren que los factores de riesgo cardiovascular evaluados en conjunto favorecen el alto riesgo de desarrollar ateroesclerosis en pacientes co lupus eritematosos sistémico.

Systemic lupus erythematosus is a chronic and multisystemic autoimmune disorder that is associated with early and severe development of atherosclerosis, thus permitting place cardiovascular diseases as the leading cause of morbidity and mortality in patients with this pathology. The present research aimed to evaluate conventional risk factors, unconventional and lupus that contribute to cardiovascular disease development in these individuals. To do this, patients with SLE (n=14 female and male n=1) were performed the following measurements: body mass index (BMI), waist circumference (WC), lipid profile (cholesterol, HDL-c, LDL -C, VLDL-C and triglycerides), uric acid, erythrocyte sedimentation rate (ESR) and fibrinogen. Where found, 85.71% (12/15) and 100% (14/15) of patients were obese, as they showed high values of BMI (38.20±5.30 kg/mm2) and the CA (92.32±7.25 cm), respectively; 100% (15/15) low serum concentrations of HDL-c (26.00±13.03 mg/dL), 93.33% (14/15) exhibited a sedentary lifestyle, 33.33% (5/15) were hypertension patients with hypotensive treatment, 33.33% (5/15) had a family history of cardiovascular disease 6.66% (1/15) elevated VLDL-C, 6.66% (1/15) hypertriglyceridemia. Also found that 20% (3/15) presented hyperfibrinogenemia (434.50±38.90 mg/dL), 26.66% (4/15) hyperuricemia (10.46±2.45 mg/dL) and 100% had values above the reference range for ESR. These results suggest that cardiovascular risk factors evaluated together favor a high risk of developing atherosclerosis with these patients.