抗核小体抗体检测在儿童系统性红斑狼疮诊断价值中的研究

儿童系统性红斑狼疮（SLE）是儿科常见的自身免疫性疾病,患儿体内产生多种自身抗体,导致多系统、多器官损伤。目前儿童SLE诊断的血清学指标以抗核抗体（ANA）、抗双链DNA抗体（抗dsDNA抗体）和抗Sm抗体为主,但这些抗体的敏感度和特异度差异较大,临床上常可以见到抗dsDNA抗体和抗Sm抗体阴性的SLE患儿。最近研究发现,在抗dsDNA抗体阴性的成人SLE患者中可以检出抗核小体抗体（AnuA）,对成人SLE诊断和疾病监测有重要意义。本研究旨在探讨AnuA检测对儿童SLE的诊断价值,并与成人SLE患者进行比较。[第一段]     

不同底物间接免疫荧光法检测细胞膜DNA抗体在儿童系统性红斑狼疮的临床价值研究

目的：比较两种细胞株为底物间接免疫荧光法( indirect immunofluorescence assay,IIF)检测细胞膜DNA( cell membrane DNA,cmDNA)抗体在儿童系统性红斑狼疮( juvenile systemic lupus erythema-tosus,JSLE)中的检测效果。评价cmDNA抗体单独及与核小体抗体( anti-nucleosome antibody,AnuA)、史密斯( Smith,Sm)抗体和双链DNA( double-stranded DNA,dsDNA)抗体联合检测对JSLE的诊断价值;探讨cmDNA抗体与临床特点的相关性。方法选取92例JSLE为研究对象,71例非JSLE风湿病患儿为对照组。留血清采用IIF分别观察培养的人B细胞株Raji、人早幼粒白血病细胞株HL60细胞膜的荧光图形;同时用IIF检测抗核抗体( antinuclear antibody,ANA);联合酶联免疫吸附法( enzyme-linked immuno sorbent assay,ELISA)和IIF检测dsDNA抗体;联合应用免疫双扩散法和免疫印迹法检测Sm抗体、ELISA法测定AnuA,收集同期临床资料。结果以两种细胞株为底物检测JSLE患儿血清cmDNA抗体,发现Raji细胞株较HL60细胞株更易复苏、荧光图形亮度更强,表达效果更好。 cmDNA抗体在JSLE组较对照组有更高的阳性率。以Raji细胞株为底物检测cmDNA抗体,cmDNA抗体的敏感性明显高于Sm抗体及dsDNA抗体(P<0．01),特异性与dsDNA抗体相似(P>0．05),但低于Sm抗体及AnuA(P<0．01)。 cmDNA抗体分别与dsDNA抗体、Sm抗体及AnuA联合检测在SLE诊断中的敏感性均明显高于单独检测( P<0．05)。cmDNA抗体与SLE疾病活动度评分无相关性( P=0．907)。结论 cmDNA抗体对儿童SLE诊断的敏感性高,特异性强,可能成为儿童SLE诊断的相对特异性抗体之一。 cmDNA抗体与dsDNA抗体、Sm抗体及AnuA联合检测可提高对儿童SLE诊断的敏感性。选择Raji细胞株为底物检测cmDNA抗体较HL60细胞株更有优势。     

抗核小体抗体在儿童系统性红斑狼疮中的诊断意义

目的 了解儿童系统性红斑狼疮(systemic lupus erythematosus,SLE)临床特点,探讨抗核小体抗体(anti-nucleosome antibodies,AnuA)与SLE临床特点的关系.方法 回顾性分析2011年4月至2017年4月在江西省儿童医院住院确诊的SLE患儿病历资料.结果 58例SLE患儿中,29例AnuA阳性与29例AnuA阴性SLE患儿比较,两组间水肿、贫血、肾功能、狼疮性肾炎的病理活动性指数、慢性指数、抗dsDNA抗体阳性率、抗组蛋白抗体阳性率、抗心磷脂抗体阳性率和补体C4下降程度等指标差异均有统计学意义.AnuA阳性SLE患儿肾脏损害程度更重,且病理损害活动度更高,抗dsDNA抗体阳性率、抗组蛋白抗体阳性率、抗心磷脂抗体阳性率更高,补体C4下降程度和贫血程度更重.结论 AnuA对SLE的诊断具有一定指导意义,并可作为SLE患儿进行肾活检的参考指标之一.     

自身抗体检测在儿童自身免疫性疾病中的意义

目的 研究抗核抗体（ANA）、ANA荧光分型、抗可溶性抗原（ENA）抗体和抗双链DNA（ds-DNA）抗体检测在儿童自身免疫性疾病中的意义。方法 对住院患儿中ANA、抗ENA，或抗ds-DNA抗体至少1项阳性者共135例进行总结，分别计算其阳性预测值（PV）。结果 ANA阳性中自身免疫性疾病的PV=0．36，ANA荧光强度与PV成正比，ANA荧光分型中细颗粒型对于SLE有较高的PV；抗ENA抗体和抗ds-DNA抗体对自身免疫性疾病PV高于ANA。结论 ANA荧光强度，抗ENA抗体和抗ds-DNA抗体阳性对自身免疫性疾病有较高的诊断价值。     

抗环瓜氨酸肽抗体用于幼年特发性关节炎诊断和鉴别诊断的临床意义

本研究用ELISA法检测抗CCP抗体,探讨它在早期幼年特发性关节炎(JIA)中的诊断和在鉴别诊断中的意义。1材料与方法1.1研究对象已确诊的JIA患儿组75例,男性43例,女性32例;年龄5～16岁。儿童SLE患儿组41例,男性18例,女性23例;年龄4～14岁。小儿SA患儿组67例,男性33例,女性34例,年龄     

抗中性粒细胞胞浆抗体与儿童风湿性疾病

目的探讨抗中性粒细胞胞浆抗体(ANCA)与儿童风湿性疾病包括系统性红班狼疮(SLE)、过敏性紫癜(HSP)及混合性风湿性疾病(MRD)肾损伤的关系.方法采用间接免疫荧光法(IIF)和酶联免疫吸附试验(ELISA)检测105例患儿于疾病急性期血清ANCA,检测并比较这些患儿肾损伤情况与ANCA的相关性.结果血清ANCA阳性率为SLE7/23(30.43%)、HSP15/64(23.44%)、MRD6/18(33.33%),其中核周型即P-ANCA18例(SLE5例、HSP9例、MRD4例);胞浆型即C-ANCA7例(SLE2例、HSP4例、MRD1例);未确定型即A-ANCA3例(HSP2例、MRD1例).比较患儿疾病急性期肾功能受损与血清ANCA水平的相关性,提示血清ANCA阳性患儿早期肾损伤率明显高于ANCA阴性患儿(P<0.05).结论本文提示ANCA可能对鉴别小儿风湿性疾病肾损伤具有重要意义,并可能成为该类疾病针对其肾损伤给予早期评价预后、选择积极治疗的重要免疫学血清指标.     

风湿病及结缔组织病

932138血清抗EVA抗体在儿童风湿性疾病中的意义/陈燕…//实用儿科临床杂志一1993,8(2)一82一83 对56例结缔组织病患儿常规进行抗核抗体(ANA)及抗DNA抗体测定,随机取样进行抗ENA抗体分析.结果:抗ENA抗体仅特异性存在儿童系统性红斑狼疮(SLE)及混合结缔组织病(MCTD)病人血清中,SLE阳性例数24/31例,MCTD为2/2例,余均阴性.在抗ENA抗体阳性的SLE病例中,抗Sm、RNP屯ssA、SSB抗体阳性率分别为87.5%,62.5%,65%和65%。血清抗ENA抗体的滴度,与ANA滴度不一致,而与荧光抗核抗体(FANA)的图型有关。出现狼疮脑炎的患儿,FANA滴度与…     

抗环瓜氨酸肽抗体和隐匿性类风湿因子免疫球蛋白M型在诊断早期幼年类风湿关节炎中的意义

目的 检测抗环瓜氨酸肽(CCP)抗体及隐匿性类风湿因子IgM型(HRF-IgM),并探讨其在幼年类风湿关节炎(JRA)早期诊断中的临床意义。方法 用人工合成CCP链为抗原检测抗CCP抗体;对27例早期诊断的JRA做动态检测,通过阳性预测值(PPV)和阴性预测值(NPV)确定抗CCP抗体和HRF-IgM对早期诊断的JRA的特异性和敏感性。结果 抗CCP抗体和HRF-IgM总阳性率分别为58.5％、65.0％。后者敏感性要高于前者,病情越重或受累的关节越多,抗体检出率越高。对早期JRA的PPV、抗CCP抗体特异性要高于HRF-IgM。当两种实验联合应用时,对具有早期关节炎表现发展成JRA的PPV为93.7％。结论 抗CCP抗体和HRF-IgM在JRA患儿均有较高的检出率,并与疾病严重程度有关。抗CCP抗体与HRF-IgM联合应用时,可使JRA的PPV进一步提高。     

系统性红斑狼疮患儿血清抗β2-糖蛋白Ⅰ抗体亚型与抗心磷脂抗体对比性分析

目的　通过分析伴有继发性抗磷脂综合征和无抗磷脂综合征的儿童系统性红斑狼疮 (SLE)血清的抗 β2 糖蛋白I( β2 GPⅠ )抗体亚型 ,对其抗心磷脂 (aCL)抗体亚型及抗磷脂综合征的临床症状进行评价。方法　对 2 0 0 0年 1月至 2 0 0 3年 9月北京儿童医院收治的SLE患儿 110例 ,采用酶联免疫吸附技术进行抗 β2 GPⅠ抗体和抗aCL抗体的测定 ,用酶标记特异性抗体进行各亚型的分析。采用脑磷脂 白陶土法进行狼疮抗凝集物的测定。同时对 6例伴有继发性抗磷脂综合征的SLE患儿进行了动态监测。结果　 110例SLE患儿中有 2 2 7%( 2 5 / 110 )抗β2 GPⅠ抗体升高 ,其中伴有继发性抗磷脂综合征的SLE组中占 5 7 1% ( 2 4 / 4 2 ) ;无继发性抗磷脂综合征的SLE组中仅占 1 5 % ( 1/ 6 8) ,两组差异具有非常显著性意义。 110例SLE患儿中有 5 1 8% ( 5 7/ 110 )抗aCL抗体升高 ,其中 ,在伴有继发性抗磷脂综合征患儿中占 6 6 7% ( 2 8/ 4 2 ) ;无继发性抗aCL抗体的SLE者中占 4 2 7% ( 2 9/ 6 8) ,两组相比 ,差异具有显著性意义。在类风湿性关节炎对照组中 ,有 32 1%的患儿抗aCL抗体呈阳性但均为低阳性。SLE患儿组与正常对照组、类风湿性关节炎对照组相比 ,差异均具有显著性意义。 6例在动态观察中抗体亚型和水平随疾病     

系统性红斑狼疮患儿肿瘤坏死因子-α、抗ds-DNA抗体水平变化

目的探讨系统性红斑狼疮（SLE）及狼疮性肾炎（LN）患儿血清肿瘤坏死因子-α（TNF-α）、抗ds-DNA抗体水平的变化及其与病情的相关性。方法选择67例SLE患儿(其中52例为LN患儿),以30例健康体检儿童为对照组,采用酶联免疫吸附法检测血清TNF-α水平,放射免疫法检测抗ds-DNA抗体水平。结果 SLE和LN患儿的血清TNF-α、抗ds-DNA抗体水平均高于对照组,差异均有统计学意义（P均<0.01）;SLE和LN患儿中活动期患儿的血清TNF-α、抗ds-DNA抗体水平均高于静止期患儿,差异均有统计学意义（P均<0.01）;67例SLE患儿TNF-α与SLE疾病活动指数、抗ds-DNA水平均呈明显正相关（P<0.01）。结论 SLE及LN患儿血清TNF-α、抗ds-DNA抗体水平升高,且与病情活动性相关。     

Usefulness of antinuclear antibody testing to screen for rheumatic diseases

OBJECTIVE: To assess the usefulness of the indirect immunofluorescence antinuclear antibody test (FANA) using human laryngeal epithelial carcinoma cells as nuclear substrate, to screen for childhood rheumatic diseases. STUDY DESIGN: A review of all FANA tests performed on children at British Columbia's Children's Hospital between 7 March 1991 and 31 July 1995. RESULTS: FANA tests were positive at titres of 1:20 or greater in 41% of all subjects tested, and in 65% of all subjects in whom the diagnosis was obtained. FANA positivity occurred in 67% of those with a rheumatic disease, compared with 64% of those with a non-rheumatic disease (p = 0.4). More girls had high titre FANA positivity than boys independent of whether or not they had a rheumatic disease (p = 0.05). At a screening serum dilution of 1:40 a positive test has a sensitivity of only 0.63, and a positive predictive value of only 0.33 for any rheumatic disease. For systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), or overlap syndrome at a screening dilution of 1:40 the test has a very high sensitivity of 0.98, but a very low positive predictive value of only 0.10, the test having slightly better characteristics for boys than girls. CONCLUSION: Although a negative FANA test makes a diagnosis of SLE or MCTD extremely unlikely, a positive test even at moderately high titres of 1:160 or higher is found so frequently in children without a rheumatic disease that a positive result has little or no diagnostic value. It is suggested that a screening serum dilution of 1:160 or 1:320 would increase the usefulness of the test, by decreasing false positive tests, without significantly increasing false negative tests for SLE or MCTD, and would have the potential for considerable cost savings.     

Tumor suppressor protein p53 and anti-p53 autoantibodies in pediatric rheumatological diseases

The tumor suppressor protein p53 plays an important role in cell cycle regulation. One of the major features in rheumatic diseases is the abnormal proliferation of lymphocytes. p53 expression in peripheral blood mononuclear cells (by flowcytometry) and serum anti-p53 antibodies (by ELISA) were therefore measured in 18 children and adolescents with juvenile rheumatoid arthritis (JRA) and 17 with systemic lupus erythematosus (SLE) in comparison to 20 healthy controls, to determine their role. p53 expression in patients was insignificantly higher than that of controls (2.28 ± 2.71% vs. 1.08 ± 1.02%, respectively, p > 0.05) with 29.4% of the patients showing values above a cut-off level of 2.55% (95th percentile of controls). SLE patients with active disease had significantly higher p53 expression compared to controls and to patients with quiescent disease although no significant correlation with ESR or complement 3 was detected. Seropositivity to anti-p53 antibodies was observed in none of controls but in 22.8% of patients, all of whom, except one, had active disease. Seropositivity to anti-p53 antibodies was more prominent in lupus nephritis than in other presentations of SLE (p < 0.05). The mean p53 expression in seropositive patients was insignificantly higher than in seronegatives. p53 expression and seropositivity to anti-p53 were slightly higher in SLE than in JRA and were not significantly affected by the mode of therapy. Thus, the overexpression of p53 in some patients with active SLE and JRA might explain the abnormal proliferation of autoreactive lymphocytes that perpetuates the inflammatory response. The presence of anti-p53 antibodies might cause malfunctioning of p53 protein interfering with its regulatory functions.     

羟氯喹在儿童患者的应用及其安全性观察

目的分析儿童使用羟氯喹的主要疾病谱,初步评价儿童使用该药物的安全性和依从性。方法以2008年1月至2019年12月在复旦大学附属儿科医院住院或出院后随访期间使用羟氯喹的528例患儿为研究对象,回顾性分析该药使用疾病谱,对其中持续使用羟氯喹超过3个月且随访超过6个月的患儿进行药物安全性及依从性评价。收集人口学信息、诊断、羟氯喹使用初始剂量、持续使用时间、累积使用剂量、相关不良反应报告,眼科检查项目与结果等资料进行分析。系统性红斑狼疮(SLE)与其他病种间持续使用时间和累积使用剂量的差异比较采用Mann-Whitney检验。结果12年共计528例患儿使用羟氯喹,其中男156例、女372例,初次用药年龄为(10.5±3.2)岁。其中风湿性疾病514例(97.4%),肺间质病变5例(0.9%)和其他系统疾病9例(1.7%)。风湿性疾病中前3位依次为SLE(316/514,61.5%),幼年型特发性关节炎(69/514,13.4%),幼年型皮肌炎(56/514,10.9%)。同期SLE诊断397例,羟氯喹使用比例最高(316/397,79.6%),且逐年增多。肺间质病变包括4例SFTPC基因缺陷相关间质性肺病。528例使用羟氯喹的患儿中397例纳入药物安全性及依从性分析,初始剂量为(4.2±1.0)mg/kg,持续使用时间为29.6(14.9,48.8)个月,最长者127个月,最大累积使用剂量为566.8 g。SLE患儿的持续使用时间(Z=-3.191,P=0.001)和累积使用剂量(Z=-5.355,P=0.001)均显著高于其他病种。所有随访患儿用药前均进行全面眼科检查,354例(89.2%)在本院眼科随访,其中65.5%(232/354)可达到每年1次及以上的定期随访。随访期间1例患儿在用药32.7个月时发生皮肤严重不良反应,无其他严重不良反应发生,无羟氯喹相关视网膜病发生,5例自行停药。结论羟氯喹主要用于SLE为主的儿童风湿性疾病中。长期使用安全性好,严重不良反应少;用药及眼科随访依从性好。     

Cardiac Operations for North American Children with Rheumatic Diseases: 1985–2005

Certain pediatric rheumatic diseases are known to affect the heart, sometimes requiring surgical intervention. The Pediatric Cardiac Care Consortium database was used to characterize cardiac surgical intervention among children with rheumatic diseases from 1985 to 2005. From this large database, the records for patients younger than 21 years who underwent cardiac surgery for any rheumatic disorder were extracted. The data collected included the type of procedure performed, the age at the time of the procedure, and the year the procedure was performed. The 261 pediatric patients identified underwent 361 cardiac surgical procedures for complications of rheumatic heart disease (RHD; 160 patients), neonatal lupus (NLE; 53 patients), Kawasaki disease (KD; 28 patients), systemic lupus erythematosus (SLE; 13 patients), and juvenile rheumatoid arthritis (JRA; 7 patients). Multiple procedures were performed for 23% of the patients. The most common procedures included pacemaker implantations among infants with NLE, coronary artery bypass grafts for KD primarily in 5- to 15-year-olds, and cardiac valve operations among adolescents with RHD, SLE, and JRA. Six perioperative deaths occurred. The proportion of annual pediatric cardiac surgical volume attributable to rheumatic diseases did not change during the period studied. Despite advances in their medical care, children with rheumatic diseases continue to sustain measurable morbidity and mortality due to the cardiovascular manifestations of their disease.     

Usefulness of antinuclear antibody testing to screen for rheumatic diseases

OBJECTIVE—To assess the usefulness of the indirect immunofluorescence antinuclear antibody test (FANA) using human laryngeal epithelial carcinoma cells as nuclear substrate, to screen for childhood rheumatic diseases.
STUDY DESIGN—A review of all FANA tests performed on children at British Columbia''s Children''s Hospital between 7 March 1991 and 31 July 1995.
RESULTS—FANA tests were positive at titres of 1:20 or greater in 41% of all subjects tested, and in 65% of all subjects in whom the diagnosis was obtained. FANA positivity occurred in 67% of those with a rheumatic disease, compared with 64% of those with a non-rheumatic disease (p=0.4). More girls had high titre FANA positivity than boys independent of whether or not they had a rheumatic disease (p=0.05). At a screening serum dilution of 1:40 a positive test has a sensitivity of only 0.63, and a positive predictive value of only 0.33 for any rheumatic disease. For systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), or overlap syndrome at a screening dilution of 1:40 the test has a very high sensitivity of 0.98, but a very low positive predictive value of only 0.10,the test having slightly better characteristics for boys than girls.
CONCLUSION—Although a negative FANA test makes a diagnosis of SLE or MCTD extremely unlikely, a positive test even at moderately high titres of 1:160 or higher is found so frequently in children without a rheumatic disease that a positive result has little or no diagnostic value. It is suggested that a screening serum dilution of 1:160 or 1:320 would increase the usefulness of the test, by decreasing false positive tests, without significantly increasing false negative tests for SLE or MCTD, and would have the potential for considerable cost savings.

     

Diagnosis of tuberculous meningitis by detection of antigen and antibodies in CSF and sera

OBJECTIVE: To evaluate diagnostic potential of three immunological tests, namely, detection of H37Rv antigen of M. Tuberculosis in CSF, detection of antibodies (IgG) against H37Rv in CSF and detection of antibodies (IgG) against H37Rv in serum for diagnosis of tuberculous meningitis in children. SUBJECTS: 50 children diagnosed as patients of tuberculous meningitis were included as cases and 48 children with CNS diseases of nontubercular etiology [pyogenic meningitis (n = 31), encephalitis (n = 10), seizure disorder of unknown etiology (n = 5), brain tumor (n = 2)] served as controls. METHODS: H37Rv antigen of M. tuberculosis was detected in CSF by Dot ELISA, and antibodies (IgG) against H37Rv in CSF and serum were detected by Plate ELISA. RESULTS: Detection of H37Rv antigen in CSF was the most sensitive (90%) and specific (95.83%) with positive and negative predictive values of 95.74% and 90.19%, respectively, followed by detection of antibodies in CSF (sensitivity-74%, specificity-89.58%, positive predictive value-88.10%, negative predictive value-76.78%). Detection of antibodies in serum had low sensitivity (50%), specificity (91.67%), positive predictive value (86.21%) and negative predictive value (63.76%). CONCLUSIONS: Detection of antigen in CSF is a rapid, sensitive and specific test for diagnosis of tuberculous meningitis in children. Detection of antibody in CSF may be useful in some cases but needs further evaluation. Detection of antibody in serum does not appear to be useful for diagnosis of tuberculous meningitis.     

Clinical and immunological profile of systemic lupus erythematosus

Pediatric onset systemic lupus erythematosus (SLE) is not uncommon and female to male ratio varies. Pediatric SLE patients have more severe disease at onset, higher rates of organ involvement and more aggressive clinical course than adults. We compared the clinical and immunological parameters among pediatric SLE and adult SLE from Western India. Twenty five children and 60 adult patients fulfilling American College of Rheumatology SLE criteria were included. Anti-nuclear antibodies, anti-dsDNA and complement (C3, C4) levels were tested. Of 25 pediatric SLE patients studied, 24% showed CNS involvement vs. 8.3% in adults SLE (P=0.0499). Lupus nephritis was seen in 75% adult patients vs. 52% among children. Hepatosplenomegaly was noted more among adult SLE 26.8% vs 12% among children. Alopecia was an exclusive features among adult SLE.     

Initial presentation of childhood-onset systemic lupus erythematosus: a French multicenter study

OBJECTIVE: To describe the clinical and laboratory manifestations of childhood-onset systemic lupus erythematosus (SLE) at presentation. STUDY DESIGN: This retrospective French multicenter study involved 155 patients in whom SLE developed before the age of 16 years. Mean patient age at onset was 11.5 +/- 2.5 years (range, 1.5-16 years). The female to male ratio was 4.5. RESULTS: The most common initial manifestations were hematologic (72%), cutaneous (70%), musculoskeletal (64%), renal (50%), and fever (58%). Thirty-two percent of children had atypical symptoms, mainly including abdominal involvement in 26 patients, which lead to negative laparotomy results for presumed appendicitis. Severe renal, neurologic, hematologic, abdominal, cardiac, pulmonary, thrombotic, and/or cutaneous manifestations occurred within the first month after the diagnosis in 40% of patients. The mean erythrocyte sedimentation rate was 72 +/- 29 mm/h, and the mean C-reactive protein value 22 +/- 21 mg/L. Antinuclear antibodies an, anti-double stranded DNA antibodies, and low C3 or C4 level were retrieved in 97%, 93%, and 78 % of patients, respectively. CONCLUSION: Initial manifestations of childhood-onset SLE are diverse and often severe. The diagnosis of SLE should be promptly considered in any febrile adolescent with unexplained organ involvement, especially when associated with an increased erythrocyte sedimentation rate.