45例抗GQ1b抗体阳性患者临床疾病谱

目的：分析具有不同临床特征的抗GQ1b抗体阳性患者的临床疾病谱。方法：回顾性分析45例抗GQ1b抗体阳性患者的临床症状、体征、辅助检查、治疗及预后等临床资料。结果：45例（男24，女21）抗GQ1b抗体阳性患者中，抗GQ1b抗体综合征32例，抗GQ1b抗体阳性吉兰巴雷综合征（GBS）10例，抗GQ1b抗体阳性慢性炎症性脱髓鞘性多发性神经病（CIDP）3例。平均年龄（49.8 ±11.5）岁。血清抗GQ1b-IgG阳性40 例，抗GQ1b-IgM阳性5例，神经节苷脂抗体重叠阳性19例。抗GQ1b抗体综合征分为：经典型Miller-Fisher 综合征（MFS）12例（43.8%），Bickerstaff脑干脑炎（BBE）3例（9.4%），伴有眼肌麻痹的GBS 5例（15.6%），不完全形式的MFS 12例 [（43.8%，包括无共济失调的急性眼轻瘫（AO）8例，急性瞳孔扩大2例，急性球麻痹1例，急性前庭综合征1例)]。10例抗GQ1b抗体阳性GBS与抗体阴性的GBS在临床经过及症状体征方面比较，差异无统计学意义（P均＞0.05），3例抗GQ1b抗体阳性CIDP中，抗GQ1b-IgM阳性2例，临床表现为经典CIDP。结论：抗GQ1b抗体综合征是一组血清抗GQ1b抗体阳性、临床表现多样的自身免疫性疾病连续谱。     

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.     

抗膜联蛋白A2抗体在抗磷脂综合征中的作用

目的 研究抗膜联蛋白A2抗体在抗磷脂综合征(APS)、系统性红斑狼疮(SLE)的血栓/病态妊娠中的可能作用.方法 先用分子克隆方法表达纯化出重组膜联蛋白A2,然后以重组膜联蛋白A2为抗原,采用酶联免疫吸附试验(ELISA)法分别检测了,101例APS患者,41例SLE合并血栓患者,124例无血栓的SLE患者及120名健康人的血清中IgG型抗膜联蛋白A2抗体水平.结果 APS组和SLE合并血栓组的IgC型抗膜联蛋白A2抗体阳性率分别为21.8%,26.8%,均品著高于单纯SLE组(6.5%)(P值均<0.0.).IgG型抗膜联蛋白A2抗体与血栓/病态妊娠有关联(P<0.01).IgG型抗膜联蛋白A2抗体对血栓/病态妊娠诊断的敏感性、特异性、预测值分别为0.232、0.935、0.805.结论 IgG型抗膜联蛋白A2抗体与APS和SLE患者的血栓/病态妊娠表现相关,将有助于一些潜在的APS患者的诊断.     

抗心磷脂抗体与系统性红斑狼疮高血压的相关性

目的 探讨抗心磷脂抗体在系统性红斑狼疮(SLE)高血压患者中的临床意义.方法 应用酶联免疫吸附法(ELISA)检测110例SLE患者和50名健康者血清中抗心磷脂抗体IgG(IgG-ACA)、抗心磷脂抗体IgM(IgM-ACA)、抗β2糖蛋白I(β2-GP1)抗体的浓度水平.结果 SLE高血压组IgG-ACA、IgM-ACA、抗β2-GP1抗体浓度水平高于SLE正常血压组、健康对照组(P＜0.05),而SLE正常血压组与健康对照组比较差异无统计学意义(P＞0.05).结论 SLE患者合并高血压时IgG-ACA、IgM-ACA、抗β2-GP1抗体浓度水平升高,提示ACA升高与狼疮性高血压的发生有关,抗心磷脂抗体检测对预测狼疮性高血压有一定参考价值.     

抗环瓜氨酸肽抗体与系统性红斑狼疮关节炎的相关性研究

目的 研究抗环瓜氨酸肽(CCP)抗体在系统性红斑狼疮(SLE)患者中的临床意义,探讨抗CCP抗体与SLE患者关节炎及骨侵蚀的关系.方法 采用酶联免疫吸附试验(ELISA)方法检测138例SLE患者血清中抗CCP抗体水平,并与SLE患者关节表现及其他临床指标进行相关性分析.结果 抗CCP抗体在SLE患者中的阳性率为13.8%(19/138).SLE患者关节炎的发生率为50.7%,关节炎组抗CCP抗体阳性率(20%)高于非关节炎组(7.4%)(P＜0.05).在SLE关节炎患者中,抗CCP抗体阳性者类风湿因子(RF)阳性率显著高于抗CCP抗体阴性者(71.4%与14.3%)(P＜0.01).而且,抗CCP抗体与RF之间显著相关(r=0.36,P=0.002).抗CCP抗体阳性的SLE患者关节炎的发生率明显高于抗CCP抗体阴性者(73.7%与47.1%,P＜0.05).138例SLE患者中有8例出现受累关节的影像学改变,与抗CCP抗体阴性患者相比,抗CCP抗体阳性患者表现出侵蚀性关节炎的比例显著为高(35.7%与5.4%,P＜0.01).在8例表现为侵蚀性关节炎的患者中有2例患者抗CCP抗体和RF均阴性,而抗RA33抗体阳性.此8例患者均满足美国风湿病学学会(ACR)1987年类风湿关节炎(RA)的分类标准.SLE相关其他临床指标分析显示,关节炎组.与非关节炎组、抗CCP抗体阳性组与阴性组之间差异均无统计学意义.结论 13.8%的SLE患者体内存在抗CCP抗体.抗CCP抗体的出现与SLE患者关节炎和骨侵蚀密切相关,并对判断SLE关节炎的预后具有重要的临床价值.     

细小病毒B19感染与系统性红斑狼疮相关性研究

目的通过检测系统性红斑狼疮(SLE)患者血清中细小病毒B19(PVB19)特异性抗体,观察B19 IgM阳性与SLE病情及活动程度的相关性,探讨PVB19感染与SLE之间可能存在的联系。方法采用德国IBL Hamburg公司PVB19-VP2-IgM、IgG酶联免疫吸附试验(ELISA)检测试剂盒,检测51例SLE患者及20名正常人血清PVB19的特异性抗体。结果51例SLE患者中B19 IgM抗体阳性11例(22%)。而正常对照组都为阴性,差异有统计学意义(P＜0．01)。根据B19 IgM阳性/阴性对SLE患者分组后发现,B19 IgM阳性组SLE疾病活动评分(SLEDAI)显著高于阴性组(P＜0．05)；B19 IgM阳性组与阴性组临床特征相比,除丙氨酸转氨酶(ALT)或天冬氨酸转氨酶(AST)上升差异有统计学意义(P＜0．05)外,其余差异均无统计学意义(P＞0．05)。对5例B19 IgM阳性的SLE患者随访2年发现,这些患者临床症状显著改善,SLEDAI评分显著下降(P＜0．05),但自身抗体水平[抗核抗体(ANA)、抗双链DNA(dsDNA)]无显著性改变(P＞0．05),ALT或AST均恢复正常。结论PVB19感染在诱发SLE活动中起作用,但与SLE预后可能无关。     

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.     

骨桥蛋白在系统性红斑狼疮中的临床意义

目的 研究血清骨桥蛋白(OPN)与系统性红斑狼疮(SLE)临床表现、实验指标、疾病活动的相关性,探讨血清OPN在SLE中的意义及SLE的发病机制.方法 用酶联免疫吸附(ELISA)法检测68例SLE患者和20名正常对照组血清中OPN的水平,并监测SLE患者的临床表现及实验室指标,分析其与OPN的相关性.结果 68例SLE患者中79%血清OPN阳性,20名正常对照组0PN均阴性,SLE组患者血清OPN阳性率及OPN水平显著高于正常对照组(P＜0.01).血清OPN阳性组的SLE患者与OPN阴性组的SLE患者相比,在年龄、性别及病程上差异均无统计学意义(P＞O.05 .血清OPN阳性组SLE患者发热、脱发、白细胞降低、肝脏损害、补体C4降低、免疫球蛋白IgA增高、蛋白尿及抗dsDNA抗体阳性的发生率明显高于OPN阴性组(P＜0.05). SLE患者血清OPN阳性率明显高于抗dsDNA抗体、抗sm抗体的阳性率,差异具有统计学意义(P＜0.01). SLE患者血清OPN水平与SLE疾病活动指数(SLEDAI)积分呈明显的正相关(r=0.292;P＜0.05);SLE活动期患者血清OPN阳性率及水平明显高于SLE缓解期患者,两组比较差异具有统计学意义(P＜O.05).结论 SLE患者血清中OPN水平升高,与SLE疾病活动性密切相关,可作为SLE的病情活动指标.     

抗心磷脂抗体与系统性红斑狼疮高血压的相关性

目的探讨抗心磷脂抗体在系统性红斑狼疮(SLE)高血压患者中的临床意义。方法应用酶联免疫吸附法(ELISA)检测110例 SLE 患者和50名健康者血清中抗心磷脂抗体 IgG(IgG-ACA)、抗心磷脂抗体 IgM(IgM-ACA)、抗β_2糖蛋白Ⅰ(β_2-GP1)抗体的浓度水平。结果 SLE 高血压组 IgG-ACA、IgM-ACA、抗β_2-GP1抗体浓度水平高于 SLE 正常血压组、健康对照组(P<0.05),而 SLE 正常血压组与健康对照组比较差异无统计学意义(P>0.05)。结论 SLE 患者合并高血压时 IgG-ACA、IgM-ACA、抗β_2- GP1抗体浓度水平升高,提示 ACA 升高与狼疮性高血压的发生有关,抗心磷脂抗体检测对预测狼疮性高血压有一定参考价值。     

格林-巴利综合征(GBS)抗-GM1和抗-GD1a lgG呈高效价滴度,可与慢性炎症脱髓鞘性多神经病鉴别

近来研究表明抗神经节苷酯(GM)1和抗-GDla IgG抗体与急性轴索性周围神经病(轴索型GBS)关系密切,而与急性炎症脱髓鞘性多神经病(脱髓鞘型GBS)无关。虽然多灶性运动神经病中抗-GM1 IgM抗体的诊断价值已经肯定,但抗-GM1 IgG在GBS中的诊断价值尚未明确。Komberg等报道高效价的抗-GM1 IgG对轴索型GBS有特异性,但70例慢性炎症脱髓鞘性多神经病(CIDP)、35例多灶性运动神经病、66例感觉运动多神经病及18例感觉性神经节病均无此自身抗体。然而,有些研究人员认为抗-GM1 IgG缺乏诊断的特异性及临床实用性。Carpo等检测抗-GD1a IgG阳性在GBS为2/73,CIDP为1/20。为此,作者对GBS和CIDP患者进行抗-GM抗体检测,以了解IgG自身抗体的特异性和临床实用性。     

Detection of serum anti-ganglioside antibodies by latex agglutination assay in Guillain-Barré syndrome: comparison with ELISA

OBJECTIVE: Rapid detection of serum anti-ganglioside antibodies in Guillain-Barré syndrome (GBS) could facilitate early diagnosis and early initiation of treatment, which might shorten the term of illness and reduce sequelae. We examined serum anti-ganglioside antibodies in patients with GBS using the latex agglutination assay developed by Alaedini and Latov (J Immunoassay 21: 377-386, 2000) with some modifications. MATERIALS AND METHODS: We used 75 sera from GBS patients, which exhibited IgG anti-GM1, GD1b, or GQ1b, or IgM anti-GM2 antibodies on previous enzyme-linked immunosorbent assay (ELISA). Blue latex beads (2.5% solution of 0.3 microm) were coated with 1 mg/ml of GM1, GD1b, GQ1b or GM2. Aliquots (4 microl) of serum and the ganglioside-coated particles were mixed and rocked on a glass slide for 30 to 40 seconds. The reaction was observed under a microscope and compared with the antiganglioside antibody titers determined with ELISA. RESULTS: Agglutination was strong in sera of which the IgM or IgG titers of anti-GM1, GD1b, GQ1b or GM2 antibodies were found to be more than 1:6,400 on ELISA except for 2 samples, but weak or absent in sera with titers of 1:3,200. Agglutination was absent in sera of which the antibody titers were less than 1:3,200 on ELISA. CONCLUSION: We could rapidly detect serum IgM and IgG anti-GM1, GD1b, GQ1b and GM2 antibodies in patients with GBS by means of the latex agglutination assay when sera exhibited high titers of the respective antibodies on ELISA. The sensitivity of our agglutination assay was much lower than that of ELISA.     

Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases: antinucleosome antibodies of the IgG3 subclass are markers of renal pathogenicity in systemic lupus erythematosus

OBJECTIVE: To study the frequency and disease specificity of antinucleosome antibody reactivity in diverse connective tissue diseases (CTD), and to determine factors, such as antibody subclass, that may influence the pathogenicity of these antibodies in relation to disease activity. METHODS: IgG and IgM antinucleosome activities on nucleosome core particles from 496 patients with 13 different CTD and 100 patients with hepatitis C were measured by enzyme-linked immunosorbent assay (ELISA). Of the patients with CTD, 120 had systemic lupus erythematosus (SLE), 37 had scleroderma (systemic sclerosis; SSc), 20 had mixed connective tissue disease (MCTD), and 319 had other CTD, including Sj?gren's syndrome, inflammatory myopathy, rheumatoid arthritis, primary antiphospholipid syndrome, Wegener's granulomatosis, Takayasu arteritis, giant cell arteritis, relapsing polychondritis, Beh?et's syndrome, and sarcoidosis. Antinucleosome-positive sera were further analyzed, by isotype-specific ELISA, for antinucleosome and anti-double-stranded DNA (anti-dsDNA) IgG subclasses. RESULTS: SLE, SSc, and MCTD were the only 3 CTD in which antinucleosome IgG were detected (71.7%, 45.9%, and 45.0% of patients, respectively). Antinucleosomes of the IgG3 subclass were present at high levels in patients with active SLE and were virtually absent in those with SSc, MCTD, or inactive SLE, and their levels showed a positive correlation with SLE disease activity. Of note, an increase in levels of antinucleosome of the IgG3 isotype was observed during SLE flares, and this increase was found to be closely associated with active nephritis. Levels of antinucleosome of the IgG1 subclass showed a trend toward an inverse correlation with SLE disease activity. No significant fluctuation in the anti-dsDNA isotype profile was observed in relation to SLE severity or clinical signs. CONCLUSION: Our data suggest that IgG antinucleosome is a new marker that may help in the differential diagnosis of CTD; antinucleosome of the IgG3 isotype might constitute a selective biologic marker of active SLE, in particular, of lupus nephritis.     

Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE

OBJECTIVE: To assay anti-ganglioside antibodies (aGM1) in sera of a large cohort of European patients with systemic lupus erythematosus (SLE) to define the prevalence of these autoantibodies in SLE; to evaluate the association of aGM1 with clinical manifestations and other autoantibodies found in SLE; and to search for aGM1 association with HLA class II alleles. METHODS: Four hundred forty-eight patients with SLE were consecutively enrolled in 8 centers from 6 European countries. All sera were tested for antinuclear antibodies by immunofluorescence on HEp-2 cells as substrate, anti-dsDNA, aGM1, aCL, abeta2-glycoprotein I (abeta2-GPI) antibodies by ELISA, and antineutrophil cytoplasmic antibodies (ANCA) by immunofluorescence and by ELISA. Genomic typing for HLA class II loci was performed by polymerase chain reaction-sequence specific oligonucleotide probe method. Clinical assessment was done at the time of enrolment. RESULTS: We found 41.9% of patients with clinical signs of neuropsychiatric involvement; 15.5% of patients were positive for aGM1, 8% of the IgG isotype and 8.6% of the IgM isotype; aGM1-IgG were associated with neuropsychiatric manifestations (NPM) (RR = 3.7), with migraine (RR = 2.4), with OBS (RR = 7.3), and with peripheral neuropathy (RR = 8.5). aGM1-IgM were associated with NPM (RR = 4) and with depression (RR = 3.4). Furthermore, the genetic study showed that aGM1-IgG were associated with HLA-DQB1*0404 (RR = 7.2) while aGM1-IgM were associated with HLA-DQB1*0605 (RR = 33.3). No associations were found between aGM1 and anti-dsDNA, aCL, abeta2GP1, or ANCA. CONCLUSION: Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition.     

Anti-ganglioside antibodies in coeliac disease with neurological disorders

BACKGROUND: Anti-ganglioside antibodies have been described in sera of coeliac patients with peripheral neuropathy and cerebellar ataxia. AIMS: To investigate the correlation between anti-ganglioside antibodies and neurological involvement in coeliac disease before and after gluten-free diet. PATIENTS AND METHODS: Twenty-two untreated coeliac patients with neurological dysfunction and 30 untreated coeliacs without neurological dysfunction, 20 patients with neurological disorders, 50 autoimmune disease and 20 blood donors were tested for anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked immunosorbent assay. RESULTS: IgG antibodies to at least one of the three antigens tested were positive in 64% of coeliac patients with neurological symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02), 50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet determined anti-ganglioside antibody disappearance in about half of coeliacs. CONCLUSIONS: A significant correlation between anti-ganglioside antibodies and neurological disorders in patients with an underlying coeliac disease has been found. Anti-ganglioside antibodies may represent a new immunological marker to identify neurological impairment in patients with coeliac disease.     

PREDOMINANCE OF IgM ANTI-U1RNP ANTIBODIES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Anti-UIRNP antibodies occur in patients with mixed connectivetissue disease (MCTD), systemic sclerosis (SSc), systemic lupuserythematosus (SLE) and other ill-defined connective tissuediseases. To associate the isotypes of anti-UlRNP antibodieswith the diagnosis of the disease, namely SLE or MCTD, sequentialsera of patients positive for anti-UlRNP antibodies by counterimmunoelectrophorcsis(CIE) (32 with SLE, 35 with MCTD) were tested for IgG and IgManti-UlRNP antibodies by enzyme-linked immunosorbent assay (ELISA)using affinity-purified UlsnRNP complexes. Results from ELISAwere confirmed by RNA precipitation. IgG RNA precipitation ofHeLa cellular extracts was performed using the bulk of the IgGfraction removed from each serum after binding to protein A-Sepharosebeads. IgM RNA precipitation was carried out on the IgM fractionof the serum bound to protein A-Scpharose-rabbit anti-humanIgM immune complexes. RNAs were electrophoresed in 10.5% acrylamide-7m urea gels and detected with the silver stain. ELISA showedthat all sera were positive to IgG anti-UlRNP, while 12 of the35 MCTD and 21 of the 32 SLE patients possessed IgM anti-UlRNP(P<0.025). IgM anti-UlRNP reactivity was found during thefollow-up in 20% of 44 sera from 17 MCTD patients and 68% of112 sera from 23 SLE patients (P<0.0001). IgG from all thesera precipitated UlRNPs. Eight of the MCTD sera also precipitatedU2RNPs and 14 of the SLE sera U2 and/or U4/U6, U5 RNPs. IgMfrom MCTD sera did not precipitate URNPs, while IgM from SLEsera precipitated predominantly UlRNPs. These data suggest thatIgM anti-UlRNP antibodies occur predominantly in patients withSLE. The occurrence of IgG anti-UlRNP without IgM is more frequentin MCTD. KEY WORDS: Anti-UIRNP, Anti-Sm, Autoanubodies, Isotypes, SLE, MCTD     

CLINICAL MANIFESTATIONS AND ANTI-(U1)snRNP ANTIBODIES: A PROSPECTIVE STUDY OF 29 ANTI-RNP ANTIBODY POSITIVE PATIENTS

Twenty-nine anti-RNP positive patients were followed prospectivelywith a mean observation time of 65 months (29–120 months).The clinical course was correlated to the presence of IgM andIgG anti-(U1)snRNP antibodies as revealed by immunoblottingfrom sequentially obtained sera. There was a striking dissociationbetween the fluctuating course, with the appearance of new manifestationsfollowed by remissions, and the stability of the anti-snRNPantibody specificities where an appearance or a disappearanceof anti-snRNP specificities was a rare phenomenon. The mainepitope recognized by the IgG antibodies was the 70 kDa proteinand of the IgM antibodies the B/B' proteins. No shift from theIgM to the IgG isotype was observed. The presence of IgG anti-70kDa and IgM anti-B/B' antibodies was highly associated withpresence of arthralgias, Raynaud's phenomenon and arthritis.Further, an association was noted between the combined presenceof IgG anti-70 kDa, anti-A and anti-C antibodies and IgM anti-B/B'and puffy hands, myositis, pulmonary fibrosis and sclerodactyly,i.e. all manifestations of mixed connective tissue disease (MCTD).On the contrary, serositis as often seen in SLE was correlatedto the presence of IgG anti-B/B' antibodies. Thus the longitudinalanalysis of the correlation between anti-snRNP antibody specificitiesand clinical manifestations support the concept of MCTD as adistinct entity. KEY WORDS: Anti-RNP antibodies, snRNP proteins, MCTD, SLE     

VH4-34 encoded antibody in systemic lupus erythematosus: effect of isotype

OBJECTIVE: To determine the clinical significance of elevated serum levels of VH4-34 encoded IgM and IgG antibodies with respect to the clinical characteristics of systemic lupus erythematosus (SLE). METHODS: VH4-34 encoded IgM and IgG immunoglobulin was measured in 95 patients with SLE by ELISA using antiidiotype monoclonal antibody (Mab) 9G4. SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Presence of VH4-34 encoded antibodies on patients' B lymphocytes was analyzed by flow cytometry using Mab 9G4. RESULTS: Fifty-two of 95 patients with SLE had elevated levels of VH4-34 encoded antibodies of IgG isotype; 17 patients with VH4-34 IgG had elevated VH4-34 of the IgM isotype. Forty-three of the 95 patients had normal levels of VH4-34 encoded antibodies. When disease severity was correlated to VH4-34 isotype, patients with circulating VH4-34 IgG but without IgM had significantly more severe disease compared to patients who had VH4-34 of both isotypes. Eighty-six percent of patients with SLE nephritis and 100% of those with central nervous system (CNS) lupus had VH4-34 IgG without IgM. In vivo, VH4-34 encoded antibodies were found to bind autologous B lymphocytes. CONCLUSION: Presence of VH4-34 IgG in the absence of VH4-34 IgM was the finding most strongly associated with severe SLE, nephritis, and CNS lupus, suggesting that isotype switching of VH4-34 encoded antibodies or loss of VH4-34 IgM encoded antibodies may influence the progression of disease in SLE.     

Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis

The objective of this paper is to investigate the association between patterns of anti-dsDNA antibody isotypes and specific clinical manifestations (categorized in renal, musculoskeletal, cutaneous, hematological, pulmonary, neurological and cardiac). Sera of 202 systemic lupus erythematosus (SLE) patients, 33 patients suffering from other autoimmune diseases and 115 healthy blood donors were analysed for anti-dsDNA antibodies by IgG-, IgA- and IgM-specific ELISA, Farr-assay and CLIF. A subset of 24 SLE patients was investigated in a longitudinal study over a period of one to six years. Disease activity of 105 SLE patients was measured according to the ECLAM score. In the cohort of SLE patients 63% were positive for the IgG class, 40% for the IgA and 57% for the IgM class specific anti-dsDNA ELISA. Sensitivity (79%) and specificity (99%) for the diagnosis of SLE appeared to be highest for the ELISA measuring all isotypes of anti-dsDNA antibodies. The concentrations of anti-dsDNA isotypes showed a strong correlation with disease activity. Analysing the relationship between IgG, IgA and IgM anti-dsDNA antibody isotypes and clinical manifestation, we found a significant association of the IgM isotype with cutaneous involvement and of the IgG isotype with lupus nephritis. The IgG/IgM ratio of anti-dsDNA antibodies represented a significant parameter to distinguish patients with lupus nephritis from those without renal involvement. In the longitudinal study, a continuous ratio under 0.8 was associated with absence of renal involvement throughout the investigated period. In conclusion, the evaluation of anti-dsDNA isotypes provides a diagnostic tool to define subsets within SLE patients with different clinical manifestations. In particular, the IgG/IgM ratio of anti-dsDNA antibodies could be used as a prognostic marker for lupus nephritis during the course of the disease.     

Anti-sulfatide reactivity in patients with celiac disease

Objective: To explore a possible significance of the presence of anti-ganglioside and anti-sulfatide antibodies in sera of adult patients with celiac disease (CD) in different clinical scenario.

Methods: We selected 22 adult patients with newly diagnosed CD and 20 age–sex matched non-CD controls. Patients’ serum was tested – before and after at least 6 months on a gluten-free diet (GFD) – for anti-GM1, GM2, GM3, GD1a, GD1b, GD3, GT1a, GT1b, GQ1b and sulfatide IgM, IgG and IgA auto-antibodies, by means of a dot blot technique and enzyme-linked immunosorbent assay (ELISA).

Results: We found the presence of auto-antibodies in untreated patients. In particular, anti-sulfatide IgG antibodies were present in 8 (36%) patients independently of the presence of neurological symptoms. Anti-sulfatide IgA antibodies were present in 3 (19%) patients. During GFD, anti-sulfatide IgG disappeared in all the patients, whereas IgA were observed in 2 patients. Anti-sulfatide, anti-GM1 and anti-GM2 IgM antibodies were also observed in 2 patients on a GFD. All the other auto-antibodies were absent and no demographic or clinical parameters were associated. Non-CD controls did not present any auto-antibody.

Conclusions: We found anti-sulfatide IgG antibodies in CD patients on a gluten-containing diet. Anti-sulfatide IgA antibodies persisted during GFD together with the occurrence of other IgM auto-antibodies. These data suggest a possible link between gluten and IgG auto-antibodies.