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Objective:To investigate the therapeutic efficacy of Golimumab in the treatment of children with refractory juvenile dermatomyositis(JDM).Methods:The clinical data of a child diagnosed with JDM in the Department of Allergy, Immunology and Rheumatology of Guangzhou Women and Children′s Medical Center in February 2019 were collected.The treatment effect was studied and literature review was conducted.Results:The patient was a 7-year-old boy with subacute onset of the disease.The illness protracted, and main manifestations included skin rashes, limb weakness, and swallowing dysfunction.Physical examination showed heliotropic rashes, Gottron papules, positive Gower, proximal limb muscle strength grade Ⅲ-Ⅳ, distal limb muscle strength grade Ⅳ, and a choking cough when swallowing fluid food.Laboratory tests revealed alanine aminotransferase (ALT) of 36 U/L, aspartate aminotransferase (AST) of 115 U/L, alkaline phosphatase of 69 U/L, lactate dehydrogenase of 941 U/L, creatine kinase of 974 U/L, hypersensitive C-reactive protein of 26 mg/L and an erythrocyte sedimentation rate (ESR) of 52 mm/1 h. Antinuclear antibody spectra were negative.Electromyography suggested myogenic damage.Thigh magnetic resonance imaging indicated diffuse abnormal signal shadows in the subcutaneous fat, muscles and muscle spaces of both hips, thighs and knee joints.The child was diagnosed with JDM, and given standardized treatment of Methylprednisolone, intravenous immunoglobulin, Methotrexate and Hydroxychloroquine sulfate.However, after the treatment, the facial rashes were still red, proximal limb muscle strength and swallowing dysfunction did not improve, the choking cough symptom still existed, and a Cushing face appeared.Recheck results showed ALT of 24 U/L, AST of 32 U/L, alkaline phosphatase of 56 U/L, lactate dehydrogenase of 216 U/L, creatine kinase of 527 U/L, hypersensitive C-reactive protein of 8 mg/L and an ESR of 15 mm/1 h. Refractory JDM was considered.After negotiating with the patient′s family members, they agreed to treat the patient with Golimumab 50 mg by subcutaneous injection once a month.Then tapered prednisone gradually, stopped Hydroxychloroquine sulfate tablets and continued to give the patient oral Methotrexate.After two doses of Golimumab 50 mg, proximal limb muscle strength and swallowing function improved markedly.After the third subcutaneous injection of Golimumab, proximal limb muscle strength improved to grade Ⅳ-Ⅴ, and he was able to go up and down stairs, squat and stand up after squatting.Besides, dysphagia and the choking cough disappeared, and skin rashes improved.Recheck results suggested a normal ESR and creatine kinase levels.Magnetic resonance imaging of thighs indicated no muscle inflammation.Conclusions:Golimumab works well in the treatment of refractory JDM and can effectively improve muscle strength.Therefore, it can be used as a treatment option for refractory JDM.
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Objective@#By studying the efficacy of interleukin (IL)-6 receptor antagonist (tocilizumab) on acute inflammation of systemin juvenile id-iopathic arthritis (sJIA) and its effect on the downstream signaling pathways and inflammatory factors of IL-6 to further reveal the role of tocilizumab in sJIA.@*Methods@#From December 2015 to December 2018, 64 sJIA children were randomly divided into two groups: 31 cases who were treated with tocilizumab+ glucocorticoid+disease-modifying anti-rheumatic drugs (DMARDs) as the tocilizumab group, 33 cases who were treated with placebo (vitamin C) + glucocorticoid+DMARDs as the control group. They were treated for one year. The levels of IL-2, IL-4, IL-6, IL-10 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of p65 and receptor activator for nuclear factor-κB ligand (RANKL) in peripheral blood mononuclear cells (PBMCs) were detected by quantitative polymerase chain reaction (qPCR). The expressions of signal transducer and activator of transcription (STAT3)/phosphates signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signaling 3 (SOCS3) before and after treatment were detected by Western blotting. The differences between groups were analyzed by variance analysis. Normal distributed data was tested by K-W test. Twenty normal control subjects came from the pediatric clinic in our hospital.@*Results@#There was no significant difference in the demographic data between the two groups (P>0.05). Among them, 2 children who were treated with tocilizumab dropped out after one month treatment and three months due to un-affordability respectively. The C-reactive protein (CRP), ferritin (FER), erythrocyte sedimentation rate (ESR) in the tocilizumab treatment group decreased significantly after 6 months and 1 year when compared with the disease control group. The concentration of IL-6 in the tocilizumab group (77±46) pg/ml, control group (82±40) pg/ml were higher than that in the healthy control group (10±3) pg/ml (F=4.683, P=0.001; F=2.581, P=0.03). After one year, the concentration of IL-6 (316±42) pg/ml in the tocilizumab group was higher than that in the disease control group (62±40) pg/ml (F=11.2, P=0.001). The expression of RANKL and p65 mRNA in treatment group was significantly higher than that in healthy control group (K-W=10.03, P<0.01; K-W=9.42, P<0.01). After one year, the expression of RANKL and p65 mRNA in treatment group was lower than that in disease control group (K-W=9.964, P<0.01; K-W=10.75, P<0.01). The expression of STAT3/p-STAT3/SOCS3 in disease control group before medication was significantly higher than that in healthy control group, while the expression of p-STAT3/SOCS3 in the treatment group was significantly higher than that in healthy control group. The expression of STAT3/p-STAT3 in the tocilizumab group was significantly lower than that in the disease control group (K-W=12.54, P<0.01; K-W=10.52, P<0.01).@*Conclusion@#Tocilizumab can effectively alleviate the symptoms of sJIA in active phase, down-regulate the expression of STAT3/p-STAT3 protein, thereby reducing the transcription of downstream nuclear factor (p65, RANKL) mRNA, thereby affecting the proliferation of synovial cells and reducing bone destruction, but has no significant effect on the secretion of IL-6.
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Objective By studying the efficacy of interleukin (IL)-6 receptor antagonist (tocilizumab) on acute inflammation of systemin juvenile id-iopathic arthritis (sJIA) and its effect on the downstream signaling pathways and inflammatory factors of IL-6 to further reveal the role of tocilizumab in sJIA.Methods From December 2015 to December 2018,64 sJIA children were randomly divided into two groups:31 cases who were treated with tocilizumab+ glucocorticoid+disease-modifying anti-rheumatic drugs (DMARDs) as the tocilizumab group,33 cases who were treated with placebo (vitamin C) + glucocorticoid+DMARDs as the control group.They were treated for one year.The levels of IL-2,IL-4,IL-6,IL-10 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA).The expressions of p65 and receptor activator for nuclear factor-κB ligand (RANKL) in peripheral blood mononuclear cells (PBMCs) were detected by quantitative polymerase chain reaction (qPCR).The expressions of signal transducer and activator of transcription (STAT3)/phosphates signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signaling 3 (SOCS3) before and after treatment were detected by Western blotting.The differences between groups were analyzed by variance analysis.Normal distributed data was tested by K-W test.Twenty normal control subjects came from the pediatric clinic in our hospital.Results There was no significant difference in the demographic data between the two groups (P＞0.05).Among them,2 children who were treated with tocilizumab dropped out after one month treatment and three months due to un-affordability respectively.The C-reactive protein (CRP),ferritin (FER),erythrocyte sedimentation rate (ESR) in the tocilizumab treatment group decreased significantly after 6 months and 1 year when compared with the disease control group.The concentration of IL-6 in the tocilizumab group (77±46) pg/ml,control group (82±40) pg/ml were higher than that in the healthy control group (10±3) pg/ml (F=4.683,P=0.001;F=2.581,P=0.03).After one year,the concentration of IL-6 (316±42) pg/ml in the tocilizumab group was higher than that in the disease control group (62±40) pg/ml (F=11.2,P=0.001).The expression of RANKL and p65 mRNA in treatment group was significantly higher than that in healthy control group (K-W=10.03,P＜0.01;K-W=9.42,P＜0.01).After one year,the expression of RANKL and p65 mRNA in treatment group was lower than that in disease control group (K-W=9.964,P＜0.01;K-W=10.75,P＜0.01).The expression of STAT3/p-STAT3/SOCS3 in disease control group before medication was significantly higher than that in healthy control group,while the expression of p-STAT3/SOCS3 in the treatment group was significantly higher than that in healthy control group.The expression of STAT3/p-STAT3 in the tocilizumab group was significantly lower than that in the disease control group (K-W=12.54,P＜0.01;K-W=10.52,P＜0.01).Conclusion Tocilizumab can effectively alleviate the symptoms of sJIA in active phase,down-regulate the expression of STAT3/p-STAT3 protein,thereby reducing the transcription of downstream nuclear factor (p65,RANKL) mRNA,thereby affecting the proliferation of synovial cells and reducing bone destruction,but has no significant effect on the secretion of IL-6.
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1,25 (OH)2D,the active form of vitamin D,plays several roles in the body,influencing bone health as well as serum calcium and phosphate levels.Further,1,25(OH) 2D plays an important role in modifying immune function including improving innate immunity and suppressing autoimmune diseases by regulating adaptive immunity.For now,there is already some understanding of the links between 1,25 (OH)2D and rheumatic autoimmune diseases like rheumatoid arthritis and system lupus erythematosus and its regulatory mechanisms involved in these diseases.However,supplement vitamin D in these patients is still in the exploratory stage.The purpose of this article is to summary the recent advances in the links between the metabolism of vitamin D and rheumatic autoimmune diseases.
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A series of clinical problems caused by mucosal immune damage in children's immune diseases need to be paid more attention.The pathogenesis is complex and the clinical manifestations are various,which may lead to misdiagnosis and missed the right treatment.The clinical phenotypes of allergic,autoimmune and inflammatory diseases,and primary immunodeficiency diseases often overlap.The immunological characteristics of mucosal immune system,the characteristics of several related clinical immune diseases,the characteristics of serum immunoglobulin (Ig) E and IgG,the difference roles between specific IgE and IgG in allergic and autoimmune diseases,the role of mucosal immune system and probiotics,mucosal immune system and vaccine,the role of mucosal immune system in the diagnosis and treatment in the related immune diseases were reviewed in this article.The treatment of IgG4-related diseases and other aspects are elaborated to show the research progress of blood IgE and mucosal immune damage in immune diseases.
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A 2-year-old male child presented with recurrent diffuse desquamative red macules all over the body,without pustules or ulcers.The patient had repeated fever,which peaked at 39.3 ℃.The patient was diagnosed with erythroderma.Whole genome sequencing showed 2 compound heterozygous mutations (c.28C＞T and c.368C＞T) in the interleukin (IL)-36RN gene.The mutation c.28C＞T was inherited from his father,leading to p.Arg10X and premature termination of amino acid transcription.The mutation c.368C＞T was inherited from his mother,causing p.Thr123 Met.No mutation was found in the IL-1RN gene in the patient.The compound heterozygous mutations c.28C＞T and c.368C＞T may be responsible for erythroderma in this child.
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Objective To explore the expression of inflammasomes (NLRP3,NLRP12) and related signal proteins in the peripheral blood mononuclear cells (PBMCs) of patients with juvenile idiopathic arthritis (JIA).Methods Samples of children with definite diagnosis of active JIA in Guangzhou Women and Childrens' Medical Center were collected retrospectively.Fifty-five cases were included,among whom 30 were systemic type and 25 were joint type.Blood samples of 22 healthy controls were collected at the same time.Peripheral blood single nuclear cell (PBMCs) were separated and DNA were extracted and reverse transcription (RT) to cDNA.Fluorescent quantitative polymerase chain reaction (PCR) was used to detect NLRP3,NLRP12,ASC,and capase-1 in groups and the difference in their expression between groups were analyzed.Enzyme linked immunosorbent assay (ELISA) was utilized to test plasma levels of interleukin (IL)-6 IL-1,IL-4,IL-10,and their correlation were analyzed.Results The expression of NLRP3,NLRP12,ASC,Capase-1 in the case group (general-group and joint-group) were higher than those in the control group (P＜0.05),but there was no significant difference in the expression levels between groups (P＞0.05).The IL-1 concentration of the case group (body-type group,joint-group) was higher than the control group (P=0.001,U=l) (P=0.001,U=14),however,the level of IL-4 of the case group (body-type group,joint-group) was not significantly different from the control group (U=662,P=0.13) (U=823,P=0.535),IL-I0 of the systemic group was higher than that of the control group (U=750,P=0.023),while there was no difference between groups (U=672,P=0.212).There were no significant difference in the levels of IL-1 (U=658,P=0.408),IL-4 (U=475,P=0.068),IL-10 (U=475,P=0.195) between groups.The NLRP3 mRNA relative expression levels of the case group and the ASC (r=0.44,P=0.013 4) was significant,in addition,IL-1 (P=0.001,R=0.58),erythrocyte sedimentation rate (ESR) (r=0.415,P=0.039),C reactive protein (CRP) (r=0.438,P=0.046) were positively correlated with NLRP12 relative mRNA expression level and ASC (r=0.583 7,P=0.007),CRP (r=0.46,P=0.031 6),ESR (r=0.003,P=0.56),CD8+ T (r=0.414,P=0.036).Conclusion The abnormal expression of JIA inflammasomes in peripheral blood mononuclear cells (NLRP3,NLRP12) may be associated with juvenile idiopathic arthritis.
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Objective To analyze the relationship between Notch signaling pathway and levels of lymphocytes and cytokines in children with juvenile idiopathic arthritis (JIA),and to explore its role in the pathogenesis of JIA.Methods Thirty-five pediatric patients with JIA [males 20 cases,females 15 cases;aged (6.5 ±4.0) years old,(0.83-15.00 years old)] and 15 healthy children [males 6 cases,females 9 cases;aged (5.0 ± 2.9) years old,(1.0-11.0 years old)] from November 2015 to February 2016 in Guangzhou Women and Children's Medical Center were included in the study.The JIA group were divided into the systemonset JIA(So-JIA) group (22 cases) and psoriatic JIA(p-JIA) group (13 cases,polyarthritis 7 cases and oligoarthritis 6 cases).The expressions of Notch signaling's receptor,ligand and target gene mRNA in peripheral blood monouclear cells (PBMC) from the JIA group and the control group were determined by quantitative real-time PCR.The levels of cytokines interleukin (IL)-1 β,IL-10,IL-6,IL-17,IL-4 and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay.Results Compared with the healthy control group,the Notch2 receptors (1.6 ± 3.2 vs.0.4 ± 0.3) expression level,Jagged1 ligand (44.0 ± 79.0 vs.11.3 ± 1.2) expression levels and the levels of target gene HES1(0.4 ±0.3 vs.0.1 ± 0.1) mRNA in the JIA group showed a significant increase,and the differences were all statistically significant (all P ＜0.05).Compared with the healthy control group,the JIA group showed an increased level of IL-1β [(182.22 ± 309.13) ng/L vs.(54.71 ± 20.33) ng/L],IL-10 [(32.99 ± 34.28) ng/L vs.(22.68 ±4.56) ng/L],IL-6 [(100.48 ±305.57) ng/L vs.(13.98 ±2.78) ng/L],IL-17 [(9.11 ± 17.57) ng/L vs.(2.42 ±0.29) ng/L] and TGF-β [(14.37 ±9.33) ng/L vs.(5.49 ±4.49) ng/L],and there were statistically significant differences (all P ＜ 0.05).The expression level of HES1 mRNA was positively correlated with STAT3 mRNA in the So-JIA group (r =0.573,P ＜0.05).The expression level of HES1 mRNA was positively correlated with CD3 + T(r =0.528),CD19 + B (r =0.480),CD3 + CD4 + TH(r =0.457) and CD16 + CD56 + NK (r =0.598) cell absolute count in the So-JIA group (all P ＜0.05).The expression level of HES1 mRNA was positively correlated with CD3 + T cell absolute count in the p-JIA group (r =0.577,P ＜ 0.05).Conclusion Imbalance between Notch pathway and lymphocytes and cytokines in children with JIA may play an important role in the pathogenesis of JIA.
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Objective To explore the expression of miR-21 and miR-19a in juvenile idiopathic arthritis (JIA) and the relationship among the key target genes (SOCS3,STAT3) in JAK/STAT pathways.Methods The venous blood from 33 cases of active JIA in Guangzhou Women and Children Medical Center were collected.All cases were divided into two groups:the systemic group (n=20),polyarthritis group (n=13).Twenty subjects were used as the normal control group.Peripheral blood mononuclear cells (PBMCs) were extracted and separated with Ficoll.miRNA was extracted and purified and real-time quantitative polymerase chain reaction (RT-PCR) was used to obtain cDNA.Target genes of miRNA were detected through Targetscan and RNA22.U6 was used for reference of miR-19a,miR-21 and β-actin were used for STAT3,SOCS3,IL-6,TNF-α mRNA.All the expression were detected by fluorescence quantitative PCR among the groups and calculated the result in standardized 2-ΔΔCT value,non-parametric test was used to test the differences.Results The expression of miR-21 were significantly reduced in the case group than the control group (Z=2.11,P=0.036),in which miR-21 was 7(7-8.5) times reduced than the SJIA group,6.49 (6-7) times than the pJIA group,the difference was statistically significant (Z=2.615,P=0.014 9;Z=2.654,P=0.0291).But no significant difference of miR-21 expression could be found between the SJIA and PJIA groups (Z=0.221,P =0.827 1).The expression of miR-19a was significantly reduced in the case group than the control group (Z=2.41,P=0.014),in which miR-19a was 11.3 (10-12.1) times to the SJIA group,12.2 (12-13.5) times to the pJIA group,the difference was statistically significant (Z=2.334,P=0.015 7;Z=2.414,P=0.026 6).But no significant difference could be detected in the miR-21 expression between the SJIA and the PJIA groups (Z=0.538,P=0.596).Software estimated that STAT3,SOCS3,TNF-α were the target genes of miR-21 and miR-19a in the JAK/STAT pathways respectively.Fluorescence quantitative PCR had shown that mRNA expression of STAT3 [6.24(2.81,7.54) and 3.97(1.81,5.75),P=0.001,0.008],TNF-α [3.03(2.07,3.80) and 3.42(2.46,4.68),P=0.002,0.001],IL-6[4.75(3.59,6.32) and 3.52(2.31,7.51),P=0.006,0.036],SOCS3[2.54(1.77,4.00) and 3.57(1.95,3.83),P=0.003,0.001] was higher in the case Group (SJIA group,the PJIA group) than the control group;STAT3 mRNA expression was negatively correlated with the miR-21 (r=-0.585 4,P=0.006 7;r=-0.613 4,P=0.044 7) and there was statistically significant difference.TNF-α,SOCS3 mRNA expression in the case group (SJIA group,PJIA group) was negatively correlated with the miR-19a.TNF-α (r=-0.664 2,P=0.001 4),SOCS3 (r=-0.790 3,P=0.000 1) of the SJIA group,was higher than those of the PJIA group TNF-α (r=-0.626 1,P=0.039 3),SOCS3 (r=-0.8824,P=0.003),the difference was significant.Conclusion The expression of miR-21,miR-19a in PBMC in the JIA patients are lower than the control group.The high expression of the target genes,miR-21,miR-19a of STAT3,SOCS3,TNF-α suggest that these genes might associate with,activating of JAK/STAT pathway.
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<p><b>OBJECTIVE</b>To explore the clinical characteristics and genetic mutations in two children with Omenn syndromes.</p><p><b>METHODS</b>Peripheral venous blood samples were collected from 2 children suspected with severe combined immunodeficiency (SCID) and their family members. The samples were subjected to RAG1 and RAG2 gene sequencing and TCR Vβ subclone analysis.</p><p><b>RESULTS</b>Both patients had recurrent infections, erythroderma rashes and alopecia baldness. One patient has fit with immunophenotype T-B-NK+, while another was consistent with typical Omenn syndrome combined with T+B-NK+ immunophenotype, IgE and eosinophil increase. Both children have carried compound heterozygous mutations of the RAG1 gene. The first patient carried c.1328 G>A (p.R443K) and c.2486-2490delGGAAA (p.R829fsX869) mutations, both were of de novel type. The second patient has carried c.1209C>T (p.R403W) and c.2892delT (p.ASN964LYSfs*14), with c.2892delT (p.ASN964LYSfs*14) being a de novel mutation. The parents of both patients were heterozygous carriers. The same mutations were not found in 100 healthy children. Both patients' 24 TCR Vβ subfamilies have presented monoclonal or oligoclonal peaks, with TCR Vβ polymorphism being severely disrupted.</p><p><b>CONCLUSION</b>Three novel mutations have been identified in two children with Omenn syndrome, which featured early onset and rapid progression. Early recognition of the disease and prompt treatment may reduce the mortality.</p>
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Adult , Female , Humans , Infant , Male , Base Sequence , DNA-Binding Proteins , Genetics , Heterozygote , Homeodomain Proteins , Genetics , Molecular Sequence Data , Mutation , Nuclear Proteins , Genetics , Pedigree , Severe Combined Immunodeficiency , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore use of interleukin-10 receptor (IL-10R) gene mutation in diagnosis and pathogenesis of neonatal inflammatory bowel disease (IBD) in 2 suspected cases.</p><p><b>METHOD</b>Two cases of sibling brothers who had suspected IBD from Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University during the year 2010-2014 were enrolled in the study. The proband, male, 26 days old, weight 3.73 kg, presented with recurrent fever, increased stool frequency since 9 days of age, and was hospitalized at the age of 6 months in 2014. The proband's brother, male, 6 months old, weight 8 kg, had repeated bloody and mucous diarrhea for more than five months, recurrent fever five days, and was hospitalized in 2010. The blood samples were collected from the children and their families for IL-10 receptor genes including IL-10 receptor α subunit (IL-10RA) and β subunit (IL-10RB) PCR amplification. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the proband IL-10RA transcripts. Sequencing was performed on the PCR products forward and reversely. Western blot analysis was used for protein expression of the proband and normal control's IL-10RA and P-STAT3 (Tyr705) expression after IL-10 stimulation, TNF-α level was detected using Human TNF-α ELISA Kit after PBMC was cultured and stimulated.</p><p><b>RESULT</b>The proband and his brother were IBD patients. Genome sequencing showed mutation in c.537G>A, namely the exon 4 and intron 4 connections changed CA/GT for CG/GT. Sequencing of the RT-PCR products and T-A clone showed that the mutation was (c.519-537del GGTGCCGGGAAACTTCAC, p.LYS173ASNfs*7), as the splice mutation. Two gene mutations were novel mutation. The parents were the mutations carrier. Both of the children were compound heterozygous mutations in IL-10RA. The Western blot analysis showed that the patient and normal children can express IL-10RA protein, however, the function of IL-10RA had obvious defects in the patient, IL-10RA downstream signaling pathways P-STAT3 had no expression. The average level of TNF-α secreted by PBMC after LPS + IL-10 co-stimulation in patient was significantly increased as compared with control group ((2 100±356) vs. (200±50) ng/L, t=9.154, P=0.001), suggesting that interleukin-10-dependent negative feedback regulation is disrupted in the patient.</p><p><b>CONCLUSION</b>IL-10 receptor mutations can cause neonatal-IBD, for which common treatment effect is poor. Early diagnosis and allogeneic stem-cell transplantation performed may save the children's life.</p>
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Objective To investigate the clinical characteristics of 34 systemic onset juvenile idiopathic arthritis (SoJIA) complicated with macrophage activation syndrome (MAS) and analyzed the gene PRF1,UNC13D,STX11,STXBP2 to figure out the genetic pathogenesis mechanism.Methods The clinical characteristics of 34 SoJIA complicated with MAS were analyzed retrospectively and coding sequences of PRF1,UNC13D,STX11 were amplified and tested.The Chi-square test was applied to compare the distribution of alleles and genotypes frequencies between SLE patients and healthy controls.Statistical significance was defined as P value ＜0.05.Results A total number of 34 SoJIA complicated with MAS were included.Boys accounted for 69％(23/34),and the median age was 6 years.85％(29/34) cases had genetic tests and four SNPS loci were detected:PRF1 c.1061 C＞T (rs885822); UNC13D c.659 C＞T (rs3744007); STXBP2 c.1483 T＞cC (rs10001) and STXBP2 c.1616 A＞G (rs6791).Compared with the control group,genotype and allele frequency of PRF1 rs885822 and STXBP2 rs10001 in MAS cases were statistical significantly different (rs885822:allele frequency x2=4.52,P=0.03 ; genotype frequency:x2=5.52,P=0.02.rs10001:allele frequencyx2=21.33,P=0.00; genotype frequency:x2=19.58,P=0.00).There was no statistical significant difference in genotype frequency and allele frequency of UNC13D rs3744007 and STXBP2 rs6791 between the MAS and control group (rs3744007:allele frequencyx2=1.89,P=0.17; genotype frequency:x2=1.59,P=0.45.rs6791:allele frequency x2=l.69,P=0.19; genotype frequency:x2=2.09,P=0.35).Persistent fever,progressive hepatos-plenomegaly,a sharp decline in blood cells counts,pleural effusion,markedly increased serum liver enzymes,hyperlipidemia were the main characteristics.Some children had mucosal bleeding,neurological dysfunction.More than 82％ children had upper respiratory tract infection before the occurrence of MAS.90％ of children were in remission,while three children had multiple organ failure and died.Conclusion MAS is a fatal complication caused by immune disturbance.Early detection and tre-atment is the key to improve the prognosis.The SNP PRF1 rs885822 and STXBP2 rs1001 may be concurrent with the pathogenesis of SoJIA-MAS.The SNP UNC13D rs3744007 and STXBP2 rs6791 may not participate in the pathogenesis of SoJIA-MAS.
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Objective To study the intestinal microflora changes in children with Henoch-Sch?nlein purpura (HSP). Methods The feces of 64 children with HSP (the experimental group) and 25 healthy children (the control group) were collected. 16S rRNA/DNA fluorescent quantitative polymerase chain reaction were performed to detect bacterial content of Lactobacillus, Biifdobacterium and Escherichia coli in feces. Results The amounts of Lactobacillus, and Biifdobacterium in the HSP group were lower than those of the healthy group, and the amounts of E.coli were higher, but the differences were not statistically signiifcant. The amounts of Lactobacillus and Biifdobacterium in the HSP children with gastrointestinal symptoms (abdominal pain, vomiting, e.g.) were signiifcantly lower than those in HSP children without gastrointestinal symptoms and in the healthy group. The difference was signiifcant (P<0.05). Conclusions It suggests that intestinal microlfora in children with HSP in acute phase may exist disorders, especially in the HSP children with gastrointestinal symptoms.
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Objective To study the clinical outcomes and safety of immunoadsorption therapy for refractory autoimmune disease in children.Methods Three boys who suffered of severe autoimmune disease-one boy suffered of severe dermatomyositis and pulmonary infection; one suffered of severe anaphylactoid purpura with alimentary tract hemorrhage and entero ablation for intestinal perforation ; other one suffered of systemic juvenile idiopathic arthritis and severe prosopo-cellular tissue infection,macrophage active syndrome,were treated with blood immunoadsorption by resin immunoadsorbent of HA280.Then evaluated the clinical outcome of 3 cases,including symptom improvement,change of serum immune globulin,complement,enzyme of liver and heart,autoantibody.Results After the treatment of immunoadsorption,the symptom of 3 cases improved obviously; the sensitivity of the corticosteroids increased; autoantibody of antinuclear antibody (ANA) and anti-cyclic citrullinated peptide antibody (CCP) changed to negative; C-reactive protein (CRP) dropped (P ＜ 0.05) ; descending scale of IgM,IgA,C3,C4 increased (P ＜ 0.05) ; the normal scale of immunoglobulin didn't changed (P ＞ 0.05) ; besides aspartate aminotransferase (AST) dropped in the case of dermatomyositis,the other enzyme of liver and heart didn't changed.Conclusions The body could be restored quickly by the treatment of immunoadsorption together with the drug; CRP in the blood could be removed by immunoadsorbent of resin; 1 or 2 times blood immunoadsorption could not change the level of enzyme,but it need to do more on severe cases,especially those with poor organ function; for the safe of the treatment of immunoadsorption for the young age,low weigh and severe cases,the operative procedure should be critical care.
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With the improvement of the therapy and the drugs we known more results in a therapeutic ambitious goals of juvenile idiopathic arthritis.Selection of individualized sequential therapy is beneficial to the recovery of the disease.
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Pediatric allergy,immunology and rheumatology (PAIR) discipline is one of the important branch of pediatrics in China.It covers the pediatric allergic diseases,immunodeficiency diseases,rheumatic diseases and the clinical and research aspect which is associated with infection and immunity including inflammation,and inflammatory diseases,et al.Though it is an interdisciplinary discipline which has a long history and being paid great attention and construction rapidly in early a decade,but it is still in the early stages of development in China.How to promote its reasonable,scientific,and further development quickly to adapt to the high-speed social medical service growth of demand in this field is an important task which we have to face to.This article reviews the discipline development history,present situation and futue trend.
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Objective To analyze the outcome of children with juvenile idiopathic arthritis (JIA) treated with recombinant human tumor necrosis factor receptor antibody fusion protein (rhTNFR:Fc) for 2 years,and to evaluate the long-term efficacy and safety as well as the related factors that affect the curative effect of rhTNFR:Fc.Methods Fifty-seven JIA patients treated with rhTNFR:Fc were followed up for 2 years.Clinical data were registered including age of onset,disease duration before rhTNFR:Fc treatment,disease activity assessment,medication before treatment,dosage regimen of infection or adverse reactions.Pearson Chi-Square statistical test and logistic regression model of binomial classification were used for statistical analysis.Results ①Twenty-two JIA cases completed 2-year therapy.Some were in the process of dosage tapering.Eight cases reached ACR Pedi 50,14 cases reached ACR Pedi 70.All of them were included in the clinical effectiveness analysis.Thirty-five cases withdrawal in 2 years because of disease remission or treatment failure or side effects or infection.Seven who withdrew and then maintained with DMARDs under the supervision of doctors were evaluated by assessment of ACR Pedi 70.They were stable at the end of 2 years,and were included for the clinical effectiveness analysis group.Nineteen cases were withdrew by the doctor because they failed to reach ACR Pedi 30 within 3 months.They were included in the treatment failure analysis.Seven cases were lost during the follow up.② The remission rate (ACR Pedi 50,70) of SO-J1A in 2 years was 33％.Oligoarthritis rate was 60％,while that of polyarthritis rate was 79％.The statistical analysis showed that different categories and RF level were significantly different in effectiveness and treatment failure (x2=31.6,P＜0.05; x2=5.488,P＜0.05).There was no significant difference in age,sex,duration before treatment,AKA,CCP,ANA between the two groups (P＞0.05).③ Logistic regression analysis showed that different categories of JIA and RF levels were correlated with therapy,P＜0.05.The relative risk (OR) value of different categories of JIA was 2.983 (P＜0.05).Negative RF might be the predictive factor for treatment response (OR =0.029,P＜0.05).④ Eight cases (2％) had recurrence and other adverse reations during treatment,the majority (7 cases) was SO-JIA.Conclusions ① The long-term therapeutic effect and safety for oligoarthritis and Polyarthritis by rhTNFR:Fc are better than SO-JIA.② Negative RF maybe the factor associated with favourable rhTNFR:Fc efficacy.③ The long-term safety of rhTNFR:Fc for SO-JIA is good.Physicians should be cautious to infection and other adverse reactions.
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The current management for juvenile dermatomyositis includes the initial use of corticosteroids followed by various conventional second-line treatments such as methotrexate and azathioprine.Intravenous immunoglobulin is a reasonable short-term treatment with proven benefit.Cyclosporine or tacrolimus have shown efficacy in juvenile dermatomyositis including those patients with interstitial lung disease,whereas mycophenolate mofetil is effective in both polymyositis and refractory dermatomyositis.The curative effect of biological agents needs to be further studied.
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Objective To study the influence of gamma globulin to serum B cell activating factor (BAFF) in therapy of neonatal thrombocytopenic purpura.Methods Fifteen cases with neonatal thrombocytopenic purpura(treatment group) were treated with gamma globulin.Serum BAFF levels of treatment group before and after treatment and 20 healthy neonates(control group) were tested.Results Serum BAFF level of the treatment group before treatment was(0.96±0.48) μg/L,which was statistically significant compared with that of the control group[(0.48 ±0.35) μg/L](P ＜0.05).Serum BAFF level of treatment group after treatment was (0.45 ± 0.37) μg/L,which was statistically significant compared with that of before treatment (P ＜ 0.05),but was not statistically significant compared with that of the control group.Conclusion Gamma globulin can play a role in the therapy of neonatal thrombocytopenic purpura by reducing the BAFF.
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Objective Through the application of recombinant human Ⅱ tumor necrosis factor-Fc function protein (rhTNFR:Fc) in the treatment of juvenile idiopathic arthritis (JIA) with randomized control study,clinical characteristic and clinical effect were summarized.Methods According to the randomized controlled principle,124 patients with JIA were divided into control group and treatment group.The basic treatment in two groups were one antirheumatic slow-acting drug,nonsteroidal drug,adrenal cortical hormone.There were no significant differences between clinical type and basic treatment in two groups (P ＞ 0.05).Sixty-two patients of JIA treated with rhTNFR:Fc by subcutaneous injection.The doses was 0.8mg /kg per week.There were 17 cases of oligoarthritis,15 cases of polyarthritis,30 cases of systemic arthritis in the treatment group and control group respectively.The basic antirheumatic drugs,nonsteroidal anti-inflamatory drugs ( NSAIDs),adrenal cortex hormone were allowed to continued.Clinical evaluation index included ACR Pedi 30,ACR Pedi 50 and ACR Pedi 70.The adverse drug reactions were recorded.Results The remission rate of ACR Pedi 30,50,70 in 2 weeks,one month,three monthes and six monthes were different in types of JIA patients in the treatment group ( P ＜ 0.05 ).The remission rate of systemic arthritis was lower than the other two groups of arthritis ( P ＜ 0.05 ).Only 44％ ACR Pedi 50 remission was achieved after three monthes medication in systemic arthritis and 41.7％ ACR Pedi 50,29.2％ ACR Pedi 70 were achieved after six monthes.The remission rate in the types of oligoarthritis and polyarthritis at different time points (2 weeks,one month,three monthes,six monthes) of ACR Pedi 30,50,70 were similar.After six monthes,more than 80％ reached ACR Pedi 50 remission,more than half of patients reached ACR Pedi 70 remission.Three cases of macrophage activation syndrome in systemic arthritis group was effective treated with rhTNFR:Fc.In the treatment group,2 cases of systemic arthritis appeared ache and discomfort after one week treatment,3 cases appeared repeated mild upper respiratory tract infection and diarrhea during treatment,including one varicella infection.The incidence of adverse reactions in the treatment group of systemic arthritis were 16.7％,Other 2 types of patients did not show adverse reaction during rhTNFR:Fc treatment.Conclusion rhTNFR:Fc has good effect on oligoarthritis and polyarthritis of JIA.The adverse reactions of six monthes were rare.The cases of systemic arthritis could reach some clinical remission,but need to guard against infection and the occurrence of adverse reactions.To whom did not respond to conventional therapy in systemic arthritis or systemic arthritis combined with macrophage activation syndrome,it could be considered with rhTNFR:Fc.