抗神经节苷脂抗体与神经精神性狼疮相关性研究

目的 探讨抗神经节苷脂抗体在神经精神性狼疮(NPSLE)中的意义.方法 采用酶联免疫吸附试验(ELISA)法,检测68份血清(包括NPSLE患者33例.无神经精神症状的狼疮患者35例)和18例脑脊液(包括NPSLE患者10例,非NPSLE的狼疮患者8例)中的抗神经节苷脂抗体IsG和IgM.结果 血清中抗神经节苷脂抗体IgG、IgM在系统性红斑狼疮患者中的阳件率分别为21%、24%,在NPSLE患者中的阳性率均为18%,在无神经精神症状的狼疮患者中的阳性率分别为22%、29%,二者在抗体水平和阳性率上差异无统计学意义(P＞0.05).脑脊液中抗神经节苷脂抗体IgG、IgM在系统性红斑狼疮患者中的阳性率分别为10/18、9/18,在神经精神性狼疮患者中的阳性率均为7/10、8/10,在非NPSLE的狼疮患者中的阳性率分别为3/8、1/8,二者在抗体水平和阳性率上差异有统计学意义(P＜0.05).结论 脑脊液中AGA与NPSLE密切相关.     

抗心磷脂抗体与神经精神性狼疮

用酶联免疫吸咐试验检测神经精神性狼疮(NPLE)、非NPLE狼疮患者,非SLE脑血管疾病患者及正常对照者血清及脑脊液中抗心磷脂抗体(ACL抗体)。结果显示NPLE组ACL抗体阳性率在血清为90％,脑脊液为33％,非NPLE狼疮组ACL阳性率在血清为44％,脑脊液为8.3％,非SLE脑血管疾病组ACL阳性率在血清为50％,脑脊液为40％,无神经精神症状的非SLE手术患者,阳性率在血清及脑脊液均为0。ACL抗体在NPLE组与其它组之间(除非SLE脑血管疾病组脑脊液中ACL抗体)有显著差别,它的检测将有助于NPLE的临床诊断。     

神经精神狼疮的诊断和治疗

目的对神经精神狼疮患者的诊断和治疗进行临床总结。方法对83例SLE患者进行回顾性分析总结。42例为神经精神狼疮(NPSLE)患者;41例为无临床神经精神症状的SLE对照组。对两组病人实验室检查,包括血液:细胞计数、电解质、肝肾功能、血糖、血脂、血沉;免疫学检测:补体、抗dsDNA抗体、可提取的核抗原(ENA)、间接荧光抗核抗体(IFANA)、抗磷脂抗体等;尿:尿常规、24h尿蛋白;脑脊液:常规、生化、脑脊液压力、细菌、霉菌学检查、免疫球蛋白检测;影像学检查:脑电图(EEG)、脑CT、脑核磁共振。治疗:对于昏迷、癫痫大发作、急性意识障碍的重症NPSLE患者治疗的甲泼尼龙(MP)起始剂量约200~500mg/d;对于一般认知障碍、磷脂抗体综合征、局灶性NPSLE(FNPSLE)的泼尼松剂量约1~2mg·kg-1·d-1。当MP剂量渐减至100mg/d应及时适当应用环磷酰胺(CTX)、甲氨蝶呤(MTX)、硫唑嘌呤(AZA)等免疫抑制剂。统计学分析:Fisher's精确试验和t检验。结果临床症状方面,NPSLE和SLE对照组比较,面部红斑(71%∶44%)和皮肤/胃肠道血管炎的发生率(67%∶27%)差异有显著性(P<0.001)。血清学检测,两组比较,仅抗磷脂抗体(aCL)和/或抗β2糖蛋白1(β2GP1)差异有显著性,其发生率分别为43%和22%(P<0.05)。42例NPSLE患者,其中33例为弥漫性NPSLE(DNPSLE),9例为F     

抗N-甲基-D-天冬氨酸型受体亚型NR2a/2b抗体与神经精神性狼疮

目的 探讨抗N-甲基-D-天冬氨酸型(NMDA)受体亚型NR2a/2b抗体(抗NR2抗体)在神经精神性狼疮(NPSLE)患者免疫发病机制中的作用和意义.方法 采用酶联免疫吸附试验(ELISA)法检测59例NPSLE患者、54例无神经精神症状的系统性红斑狼疮(SLE)患者血清及20例NPSLE患者脑脊液中抗NR2抗体的水平,评价抗NR2抗体与NPSLE的临床表现、病情活动度评分(SLEDAI)、抗dsDNA抗体水平、抗核糖体P蛋白抗体、抗核抗体(ANA)、抗Sm抗体的相关性.结果 59例NPSLE患者血清中的抗NR2抗体水平显著高于54例非NPSLE患者.同时2组患者SLEDAI评分、抗Sm抗体阳性率、抗dsDNA抗体水平及抗核糖体P蛋白抗体水平差异均有统计学意义;59例NPSLE患者中,15例器质性脑病(认知功能障碍、记忆力减退)患者血清中的抗NR2抗体水平显著高于其他NPSLE患者;20例NPSLE患者脑脊液中仅有2例抗NR2抗体高滴度阳性,二者血清中的抗NR2抗体同样高滴度阳性,此2例患者均表现为认知功能障碍、记忆力减退,二者预后差.结论 检测SLE患者血清中的抗NMDA受体亚型NR2a/2b抗体对于NPSLE具有初步筛选作用;在表现为认知功能障碍、记忆力减退的NPSLE患者的血清及脑脊液中存在高滴度的抗NMDA受体亚型NR2a/2b抗体.     

抗细胞膜DNA抗体的测定及其在系统性红斑狼疮诊断中的意义

目的建立抗细胞膜DNA(mDNA)抗体测定的方法,研究其在系统性红斑狼疮(SLE)诊断中的敏感性和特异性,以及与SLE临床特点及免疫学异常的关系.方法检测SLE患者、疾病对照组和正常对照组血清中的抗mDNA抗体,并分析SLE患者的各种临床表现及实验室指标与抗mDNA抗体的关系.同时研究细胞膜DNA分子在不同细胞表面的表达,用DNA酶、RNA酶及胰酶鉴定抗原性质.结果抗mDNA抗体在SLE中检测敏感性73.3%(152/207),特异性96.4%,疾病对照组阳性率5.4%(9/167),82名正常对照组均为阴性,抗mDNA抗体阳性率在SLE组明显高于疾病对照组和正常对照组(P＜0.01).抗mDNA抗体在其他自身抗体阴性的SLE患者中有较高的检出率,在抗双链DNA(dsDNA)抗体、抗Sm抗体、快速狼疮因子(DNP)、抗组蛋白抗体(AHA)、抗核小体抗体(AnuA)阴性的SLE患者中抗mDNA抗体的阳性率分别是73.8%、62.7%、65.3%、57.8%和51.6%.该抗体阳性组SLE患者皮疹,脱发,关节痛,白细胞和C3、C4减低及IgG、IgA、IgM升高较为常见,但与SLE患者病情活动指数无关.本文还证实细胞膜DNA在人B细胞、T细胞上均有表达,以Raji细胞株表达较好.用DNA酶预处理的细胞涂片再行检测后膜荧光图形消失,而用RNA酶、胰酶预处理后并不消失,证实其为膜DNA抗原.结论抗mDNA抗体是一种诊断敏感性高、特异性强的SLE血清学指标之一,尤其对抗dsDNA、抗Sm、抗DNP、AHA、AnuA阴性的SLE的诊断有参考意义.     

抗神经元抗体的检测及其在狼疮中枢神经系统病变中的临床应用研究

目的　建立检测抗神经元抗体 (anti neuronalantibodies,anti N)的细胞 ELISA方法 ,并评价其对系统性红斑狼疮中枢神经系统病变 (CNS SLE)的诊断价值。方法　以 1%多聚甲醛固定的SK N MC成神经瘤细胞株为抗原 ,采用细胞 ELISA方法 ,检测 12 3份血清 (包括CNS SLE 2 8例 ,无中枢神经系统受累的SLE 2 2例 ,其他结缔组织病 36例 ,正常血清 37例 )和 138份脑脊液 (包括CNS SLE 38例 ,无中枢神经系统受累的SLE 2 9例 ,其他结缔组织病 12例 ,有神经精神症状的其他疾病 5 9例 )中anti N。结果　血清中anti N在SLE中阳性率为 6 2 0 % (31/ 5 0 ) ,特异性为 91 8% ;脑脊液中anti N在CNS SLE中阳性率为 47 4% (18/ 38) ,特异性为 89 7% ,而无中枢神经系统受累的SLE (non CNS SLE)阳性率仅为 10 3 % (3/ 2 9) ,且抗体水平低于前者 ,二者在抗体水平和阳性率上差异存在显著性 (P均 <0 0 0 1) ;以意识障碍 /精神症状为主要表现的CNS SLE脑脊液中该抗体阳性率最高 ,分别为 75 0 %和 72 7% ,显著高于其他类型CNS SLE (P =0 0 1) ;8例CNS SLE患者治疗前后脑脊液中anti N水平分别为 0 47± 0 2 2和 0 2 2± 0 0 6 ,二者之间差异有显著性 (P <0 0 5 )。结论　血清中anti N对诊断SLE特异性较高 ;脑脊液中anti N是     

抗核小体抗体对系统性红斑狼疮的诊断价值及临床意义

目的评价抗核小体抗体(AnuA)对系统性红斑狼疮(SLE)诊断的敏感性和特异性。方法选取2004-01—2004-12天津市第一中心医院风湿免疫科住院患者及门诊健康体检者,用酶联免疫吸附法(ELISA)检测64例SLE患者、46例疾病对照组和30例正常对照组血清中的AnuA。结果64例SLE患者血清AnuA阳性率为73·44%,46例疾病对照组为13·04%,正常对照组全部为阴性;AnuA对SLE诊断的敏感性和特异性分别为73·44%、88·68%。AnuA在狼疮肾炎中的阳性率比在非狼疮肾炎中高(χ2=5·246,P=0·022)。在抗dsDNA抗体、抗Sm抗体、抗组蛋白抗体(AHA)阴性的SLE患者中AnuA阳性率分别为60·71%、69·57%、64·10%。结论AnuA在SLE血清中水平明显增高,AnuA测定在SLE诊断和治疗中有重要意义,特别对抗dsDNA抗体、抗Sm抗体、抗组蛋白抗体阴性的SLE的诊断有重要意义。     

抗核小体抗体在系统性红斑狼疮诊断中的意义

目的探讨抗核小体抗体(AnuA)在系统性红斑狼疮(SLE)诊断中的敏感性、特异性及其与疾病活动的相关性。方法采用ELISA检测SLE组、疾病对照组、正常对照组血清中的AnuA,将AnuA与疾病活动度(以SLEDAI评分)、抗ds-DNA抗体、抗Sm抗体等指标进行比较。结果AnuA在SLE中的阳性率高于作为SLE诊断标准中的抗ds-DNA抗体及抗Sm抗体,而抗ds-DNA抗体及抗Sm抗体阴性患者的AnuA阳性率仍可达到32.2%和57.4%。结论AnuA对SLE诊断的敏感性高、特异性强,且与病情活动呈正相关,可作为诊断和反映SLE病情活动的新指标。     

神经精神狼疮与自身抗体

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种累及多系统的自身免疫性疾病,其发病与血清具有多种自身抗体相关[1].累及到中枢神经系统并伴有精神障碍称为神经精神狼疮(NPSLE),NPSLE临床表现复杂多样,中枢、外周及自主神经系统均可受累,它以认知功能障碍和记忆力减退为临床特征,是SLE患者最常见、最严重的并发症.SLE若累及到中枢神经系统一般表示预后很差,常导致病死率增加[2].迄今为止,在SLE中已证实存在约200种自身抗体,并且数量上还在不断增加[3].然而,只有少数自身抗体被证实可作为诊断标志物,在评估疾病的活动度、预测疾病的分型或预后方面具有一定的临床意义或价值.而被证实在SLE发病机制中有因果关系的自身抗体更是屈指可数[4-5].因此,多数与SLE相关的自身抗体被解释为继发于组织损伤的免疫反应或B细胞多克隆活化后自身抗体数量的增加[6-8].目前认为,在SLE中发现抗磷脂抗体、抗N-甲基-D-天(门)冬氨酸(NMDA)受体抗体、抗神经元抗体等自身抗体有助于NPSLE的诊断,这些自身抗体也被认为是与NPSLE相关的几个特异自身抗体[4,9-13].     

系统性红斑狼疮患者抗核糖体P0蛋白抗体的临床意义

目的 探讨系统性红斑狼疮(SLE)患者抗核糖体P0蛋白抗体的临床意义.方法 采用线性免疫分析法和免疫印迹法检测49例SLE患者及61例其他结缔组织病患者血清抗P0抗体和抗核糖体抗体(rRNP),分析抗P0抗体与rRNP抗体在SLE和其他结缔组织病中阳性率的差异及抗P0抗体与SLE临床表现和其他自身抗体的关系.结果 SLE患者中抗P0抗体的阳性率为36.7%,rRNP抗体的阳性率为6.1%,二者之间差异有统计学意义(P＜0.01);抗P0抗体在其他结缔组织病中均为阴性.在SLE患者中,抗P0抗体阳性组皮疹的发生率为77.8%,阴性组为35.5%(P＜0.05);抗SmD1抗体的阳性率在抗P0抗体阳性组中为61.1%,在阴性组中为19.4%(P＜0.01).抗P0抗体对诊断SLE的敏感性为36.73%,特异性为100%,阳性预测值为100%,阴性预测值为66.30%.结论 抗P0抗体对诊断SLE的特异性强,阳性预测值高.抗P0抗体与SLE皮疹和抗SmDl抗体阳性相关.     

Neuropsychiatric manifestations in pediatric systemic lupus erythematosus: a 20-year study

The objective of this study was to investigate the manifestations, treatment and outcome of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (SLE) patients. The charts of 185 pediatric patients with SLE diagnosed between 1985 and 2005 in a tertiary referral hospital were retrospectively reviewed. NPSLE were defined using the American College of Rheumatology NPSLE case definitions. NPSLE developed in 34.6% (64/185) of the patients. The mean onset age was 15.2 years. Fourteen patients (21.9%) had NP manifestations on initial diagnosis of SLE. The median duration from the onset of SLE to NP manifestation was 11 months. The most frequent NP manifestations were seizure disorder (84.4%), ischemic stroke (28.1%) and psychosis (21.9%). However, the prevalence of manifestations of NPSLE might be underestimated by the retrospective design of our study. Higher mean C3/C4 levels, less percentage of anti-dsDNA antibodies elevation and higher percentage of elevated anticardiolipin antibodies were observed in NPSLE events than in non-NPSLE events (P < 0.05). The mortality rate of NPSLE patients decreased from 52.2% in 1985-1994 cohort to 27.8% in 1995-2005 cohort. In the past 10 years, the leading cause of death in NPSLE patients was NPSLE itself. NPSLE is common in pediatric SLE patients. It has diverse manifestations and a high mortality.     

The heterogeneity of neuropsychiatric systemic lupus erythematosus is reflected in lack of association with cerebrospinal fluid cytokine profiles

The objective was to study the occurrence of autoantibodies and cytokines in serum and cerebrospinal fluid (CSF) in neuropsychiatric systemic lupus erythematosus (NPSLE). In total, 28 consecutive patients with NPSLE and 16 systemic lupus erythematosus (SLE) patients without neuropsychiatric involvement (non-NPSLE) were studied. IFN-alpha, IL-6, IL-10, soluble terminal complement complex (TCC), anti-ribosomal P protein antibodies (anti-P) and anti-cardiolipin antibodies (aCL) were measured in serum and CSF by immunoassays. Analyses of white blood cell differential count, CSF-albumin/serum-albumin ratio, IgG-index in CSF and isoelectric focusing in serum and CSF were also performed. CSF specimens from 23 healthy individuals were used as controls. IFN-alpha was elevated in the CSF of 5 of 28 NPSLE patients compared to three of 14 among the non-NPSLE patients. IL-6 was elevated in CSF in three of 26 NPSLE patients. Normal concentration of IL-10 was found in CSF in all 27 NPSLE-patients analysed. IFN-alpha in serum was elevated in 18 of 28 NPSLE patients. No distinct clinical phenotype was related to elevated cytokine concentration in serum or CSF. One patient with cerebral involvement complicated by progressive multifocal leukoencephalopathy displayed a very high IFN-alpha concentration in serum. High concentration of TCC was present in CSF from only one patient with systemic vasculitis and focal cerebral symptoms. In conclusion, the results of this study suggest that the diagnostic value of serum and CSF concentrations of IFN-alpha, IL-10, IL-6 and TCC is limited in unselected neuropsychiatric SLE, probably due to the heterogeneity of NPSLE pathogenesis.     

Antineurofilament antibody evaluation in neuropsychiatric systemic lupus erythematosus. Combination with anticardiolipin antibody assay and magnetic resonance imaging

We used Western blot analysis to examine the occurrence and titer of antibody to cytoskeletal neurofilament protein antigens in patients with neuropsychiatric manifestations of systemic lupus erythematosus (SLE) and in controls. Twenty-two patients with neuropsychiatric SLE (NPSLE) had an increased incidence of antineurofilament antibody (ANFA) compared with 34 patients with SLE without neuropsychiatric symptoms, 78 patients with other disease processes, and 22 healthy controls. ANFA were found to be directed against the 205,000- and 160,000-dalton proteins of the neurofilament triplet. Patients with a diffuse NPSLE clinical presentation had the greatest frequency of serum ANFA (7 of 12, 58%) compared with all other groups examined. Magnetic resonance imaging and serum anticardiolipin antibody testing were also performed in selected patients with NPSLE. Patients with a focal clinical presentation of NPSLE, positive magnetic resonance imaging findings, and negative serum ANFA had significantly elevated levels of anticardiolipin antibody.     

Raised monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebrospinal fluid of patients with neuropsychiatric lupus

BACKGROUND: An imbalance in cytokine homoeostasis is thought to have a key role in the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), and recently, a role for chemokines has been noted. OBJECTIVE: To compare concentrations of monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebral spinal fluid (CSF) of patients with SLE, and with and without neuropsychiatric symptoms. METHODS: CSF was obtained from 185 patients with SLE: 96 with NPSLE and 89 patients with SLE without neuropsychiatric symptoms (non-NPSLE patients). MCP-1/CCL2 concentrations were measured with an ELISA. RESULTS: The average concentration of CSF MCP-1/CCL2 in patients with NPSLE was 1959 pg/ml, and in non-NPSLE patients 712 pg/ml. The average MCP-1/CCL2 concentration was significantly higher in the NPSLE group than in the non-NPSLE group (p<0.001). In one representative patient with NPSLE, MCP-1/CCL2 levels in the CSF decreased in parallel with a decline in neuropsychiatric symptoms. CONCLUSIONS: CSF MCP-1/CCL2 levels are higher in patients with NPSLE than in non-NPSLE patients. MCP-1/CCL2 may have an important role in the expression of NPSLE. These results indicate that CSF MCP-1/CCL2 reflects an inflammatory activity in the brain, suggesting that it might be used as a diagnostic tool and a monitor for therapeutic responses in patients with NPSLE.     

Seroprevalence and specificity of NMO-IgG (anti-aquaporin 4 antibodies) in patients with neuropsychiatric systemic lupus erythematosus

Neuropsychiatric manifestations are present in 30–40% of patients with systemic lupus erythematosus (SLE). Recently, antibodies to aquaporin-4 (termed AQP4-Ab, or NMO-IgG), a water channel protein, were reported to be present in a subset of patients with SLE and neurological involvement. To evaluate the syndrome specificity and prevalence of serum NMO-IgG/anti-AQP4 antibodies in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Sera of 76 patients with SLE and neurological symptoms, 50 of whom met the ACR case definitions of NPSLE, were tested for AQP4-Ab in an indirect immunofluorescence assay employing HEK293 cells transfected with recombinant human AQP4. Only one of the examined sera was positive for NMO-IgG/AQP4-Ab. This patient suffered from TM, ranging over two vertebral segments on spinal MRI. None of the 75 NPSLE without TM was found to be seropositive for NMO-IgG/AQP4-Ab. NMO-IgG/AQP4-Ab in NPSLE were present only in a patient with TM and were not detectable in NPSLE patients with other neurological manifestations. Testing for NMO-IgG/AQP4-Ab positivity should be considered in patients presenting with SLE and TM. Non-longitudinally extensive lesions do no not exclude NMO-IgG/AQP4-Ab in patients presenting with SLE and TM.     

Quantitative electroencephalography: A new approach to the diagnosis of cerebral dysfunction in systemic lupus erythematosus

Objective. Neuropsychiatric manifestations are common in patients with systemic lupus erythematosus (SLE), but accurate diagnosis is often difficult. We conducted a prospective study to determine the utility of neurometric quantitative electroencephalography (QEEG) as an indicator of cerebral dysfunction in SLE patients. Methods. Fifty-two SLE patients were divided into 4 groups based on the results of neuropsychiatric evaluations. These included patients with objective evidence of neuropsychiatric SLE (NPSLE), patients with neuropsychiatric symptoms, patients with no evidence of NPSLE, and patients with a prior history of NPSLE. All QEEG findings were compared with data in an age-regressed normative database and with findings in an independent sample of normal subjects. Results. QEEG sensitivity was 87%, and specificity was 75%. QEEG results were abnormal in 74% of the SLE patients with neuropsychiatric symptoms and in 28% of the patients with no evidence of active NPSLE. QEEG profiles varied as a function of the severity and type of neuropsychiatric manifestation present. Within this patient population, QEEG was more sensitive than magnetic resonance imaging, computed tomography scanning, or conventional EEG. Conclusion. Neurometric QEEG may be a sensitive indicator of cerebral dysfunction in patients with NPSLE and can differentiate patients with diverse neuropsychiatric manifestations. When combined with a careful clinical history and evaluation, QEEG provides information that may be useful for the early detection of NPSLE and for serial evaluation of disease activity and treatment efficacy.     

Quantitative electroencephalography. A new approach to the diagnosis of cerebral dysfunction in systemic lupus erythematosus.

OBJECTIVE. Neuropsychiatric manifestations are common in patients with systemic lupus erythematosus (SLE), but accurate diagnosis is often difficult. We conducted a prospective study to determine the utility of neurometric quantitative electroencephalography (QEEG) as an indicator of cerebral dysfunction in SLE patients. METHODS. Fifty-two SLE patients were divided into 4 groups based on the results of neuropsychiatric evaluations. These included patients with objective evidence of neuropsychiatric SLE (NPSLE), patients with neuropsychiatric symptoms, patients with no evidence of NPSLE, and patients with a prior history of NPSLE. All QEEG findings were compared with data in an age-regressed normative database and with findings in an independent sample of normal subjects. RESULTS. QEEG sensitivity was 87%, and specificity was 75%. QEEG results were abnormal in 74% of the SLE patients with neuropsychiatric symptoms and in 28% of the patients with no evidence of active NPSLE. QEEG profiles varied as a function of the severity and type of neuropsychiatric manifestation present. Within this patient population, QEEG was more sensitive than magnetic resonance imaging, computed tomography scanning, or conventional EEG. CONCLUSION. Neurometric QEEG may be a sensitive indicator of cerebral dysfunction in patients with NPSLE and can differentiate patients with diverse neuropsychiatric manifestations. When combined with a careful clinical history and evaluation, QEEG provides information that may be useful for the early detection of NPSLE and for serial evaluation of disease activity and treatment efficacy.     

Antibodies to microtubule-associated protein-2 in the cerebrospinal fluid are a useful diagnostic biomarker for neuropsychiatric systemic lupus erythematosus

Objective: Previous reports indicate that serum anti-microtubule-associated protein 2 (MAP-2) antibodies are common in sera from patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Differential diagnosis of NPSLE is occasionally difficult because of differential diagnosis which can mimic NPSLE. Therefore, specific biomarkers for NPSLE are needed. We conducted this study to clarify whether cerebrospinal fluid (CSF) anti-MAP-2 antibodies are a useful diagnostic biomarker for NPSLE.

Methods: Enzyme-linked immunosorbent assay was conducted to measure CSF concentrations of anti-MAP-2 and anti-ribosomal P antibodies and of IL-6 in NPSLE patients (n?=?24) and non-NPSLE controls (n?=?17). The non-NPSLE controls consisted of systemic lupus erythematosus patients with neuropsychiatric symptoms caused by non-NPSLE conditions (n?=?10) and patients with other connective tissue diseases (n?=?7).

Results: Significantly higher anti-MAP-2 antibody titers were found in the CSF of patients with NPSLE versus non-NPSLE controls. The prevalence of anti-MAP-2 antibodies was 33.3% (8/24) in NPSLE patients when a positive cutoff value was 3 standard deviations above the mean optical density of non-NPSLE controls. None of the controls had anti-MAP-2 antibodies in their CSF. Both anti-ribosomal P antibody titers and concentration of IL-6 in the CSF were significantly higher in patients with NPSLE having anti-MAP-2 antibodies than in patients with non-NPSLE controls.

Conclusion: Anti-MAP-2 antibodies could be detected in the CSF of 33.3% of patients with NPSLE, and its presence was highly specific for NPSLE. We propose that CSF anti-MAP-2 antibodies are a novel and useful diagnostic biomarker for NPSLE.     

Lymphocytotoxic antibodies in systemic lupus erythematosus are associated with disease activity irrespective of the presence of neuropsychiatric manifestations

OBJECTIVES: To evaluate the association of the presence of lymphocytotoxic, anti-beta2-glycoprotein I (anti-beta2-GPI) and anti-ribosomal P (anti-P) antibodies in patients with systemic lupus erythematosus (SLE), presenting or not neuropsychiatric (NP) manifestations, stratified according to the activity of the disease. METHODS: A total of 138 patients with SLE (59 with active NPSLE, 49 with active non-NPSLE, and 30 with inactive disease) and 57 healthy controls were studied. Disease activity was assessed by the SLE Disease Activity Index (SLEDAI). The presence of lymphocytotoxic antibodies was assessed using a complement-dependent lymphocytotoxicity assay. The presence of anti-beta2-GPI and anti-P antibodies was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Lymphocytotoxic antibodies were detected primarily in patients with active disease, that is in 35 out of 59 (59.3%) NPSLE and 23 out of 49 (46.9%) non-NPSLE patients, whereas only four out of 30 (13.3%) inactive SLE patients and none of the healthy controls exhibited the autoantibody. The frequency of lymphocytotoxic antibodies in active SLE patients, considered as a whole or stratified into NPSLE or non-NPSLE, was significantly increased in relation to inactive SLE patients (p<0.001 for each comparison). No significant difference was observed when comparing active NPSLE with non-NPSLE patients. No associations were observed between the presence of anti-beta2-GPI or anti-P antibodies and the activity of SLE or the presence of lymphocytotoxic antibodies. CONCLUSIONS: Lymphocytotoxic antibodies occurred more frequently in patients with active SLE than in patients with inactive disease, irrespective of the presence of NP manifestations, a finding that is similar to classical biomarkers of lupus activity (anti-dsDNA and complement). These results indicate that the assessment of the presence of lymphocytotoxic antibodies may be an additional useful tool for the evaluation of SLE activity.     

Antiribosomal P protein antibodies in cerebrospinal fluid are associated with neuropsychiatric systemic lupus erythematosus

OBJECTIVE: To investigate whether antiribosomal P protein antibodies (anti-P) are present in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE), and if presence of anti-P in CSF is more strongly related to the appearance of neuropsychiatric SLE (NPSLE) than anti-P in serum. METHODS: CSF and serum samples from 70 patients with SLE were used. Patients were divided into 4 groups: 21 patients with neurologic syndromes of the central nervous system (CNS); 19 patients with diffuse psychiatric/neuropsychological syndromes; 10 patients with complex presentations (neurologic syndromes of the CNS plus diffuse psychiatric/neuropsychological syndromes); and 20 patients without NPSLE based on diagnostic criteria for 19 NPSLE syndromes proposed by the American College of Rheumatology. IgG anti-P in CSF and serum samples were detected by Western blotting using rat liver ribosomes. Inhibition assay was performed using 5 anti-P-positive CSF samples preincubated with synthetic ribosomal P peptide. Western blotting results were compared with those from ELISA with synthetic ribosomal P peptide as antigen. The association of CSF and serum anti-P with NPSLE was analyzed. RESULTS: CSF and serum IgG anti-P by Western blotting were detected, respectively, in 20 (28.6%) and 32 (45.7%) of 70 patients. The presence of IgG anti-P by Western blotting in the CSF was supported by positive results in the inhibition assay and significant association with CSF IgG anti-P titers by ELISA. The frequency of CSF anti-P by Western blotting in SLE patients with serum anti-P was significantly higher than in SLE patients without serum anti-P (18/32 vs 2/38; p < 0.001). The frequency of CSF anti-P by Western blotting in patients with NPSLE was significantly higher than in patients without NPSLE (19/50 vs 1/20; p < 0.01). The frequency of CSF anti-P by Western blotting in the group with complex presentations (10/10) was significantly higher than in the other 3 groups [neurologic syndromes of CNS (5/21); diffuse psychiatric/neuropsychological syndromes (4/19); and patients without NPSLE (1/20)] (p < 0.001). The frequency of serum anti-P by Western blotting in patients with NPSLE was not significantly higher than in patients without NPSLE (25/50 vs 7/20; p = 0.192). CONCLUSION: These results suggest that the presence of IgG anti-P in CSF of SLE patients may be involved in the appearance of NPSLE, especially in complex presentations. Measurement of IgG anti-P in CSF by Western blotting may be more useful for diagnosis of NPSLE than measurements in serum.