Anti-Sm: Its predictive value in systemic lupus erythematosus

Summary The clinical manifestations of 131 rheumatic disease patients with anti-Sm antibody were studied. A variety of standard tests was utilized in the study, namely, the FANA test with mouse kidney as substrate for the assay of ANA, the Crithidia test for anti-double stranded DNA (anti-dsDNA) and double immunodiffusion for detecting antibodies to extractable nuclear antigens. The patients were grouped according to the presence of anti-Sm alone, or anti-Sm with some other antibodies. There were 17 with anti-Sm alone; 55 with anti-Sm + anti-RNP; 15 with anti-Sm + anti-dsDNA; and 44 with anti-Sm + anti-RNP. The result of our study showed that although anti-Sm could be found in other diseases, it was exclusively detected in SLE only if anti-dsDNA was also present. Further, the SLE patients with anti-Sm alone had more frequent central nervous system manifestations than other groups of patients. The renal manifestation was observed more frequently in the group of SLE patients with anti-Sm + anti-dsDNA (92.9%). Among other major manifestations, haematologic involvement had a tendency to be less common in the group of patients with anti-Sm alone. The study concludes that the presence of anti-Sm antibody may be of some value to predict the clinical outcome.     

Relation between serological data at the time of biopsy and renal histology in lupus nephritis

Summary As autoantibodies are thought to participate in the pathogenesis of renal inflammation in systemic lupus erythematosis (SLE) we investigated associations between serological markers of disease activity in SLE and the activity of renal histopathological lesions in thirty-five patients with lupus nephritis (LN). We found the following prevalence of serum auto-antibodies in LN: IgG antinuclear antibodies (ANA) 100%, IgM ANA 69%, IgA ANA 60%, IgG anti-dsDNA 60%, IgM antidsDNA 71%, IgA anti-dsDNA 60%, anti-RNP 20%, anti-Sm 14%, anti-SSA 31%, anti-SSB 14%, anti-histone 37%, anti-cardiolipin 80% and antibody to ribosomal protein (anti-P) 6%. No correlation was found between serological parameters and the WHO-classification of biopsies. The activity-index of histological lesion, assessed according to the NIH-renal histology scoring system, correlated with IgM ANA and IgM anti-dsDNA titers. Of all the specific features of histological renal inflammation, glomerular proliferation showed the best overall correlation with serological parameters of disease activity. Anticardiolipin antibodies were correlated with overall disease activity, but not with renal histological activity. Thus, serological markers of disease activity did not adequately reflect the amount of renal inflammation in LN and cannot replace renal biopsy as a diagnostic tool.     

Anti-tubulin-α-1C autoantibody in systemic lupus erythematosus: a novel indicator of disease activity and vasculitis manifestations

A variety of autoantibodies has been involved in the pathogenesis of systemic lupus erythematosus (SLE), some of which are well known and applied as disease biomarkers. This study aimed to determine the prevalence of a novel autoantibody, anti-tubulin-α-1C, in patients with SLE and investigate its clinical significance. Anti-tubulin-α-1C autoantibody levels were determined by enzyme-linked immunosorbent assay (ELISA) in 128 SLE patients, 38 primary Sjögren’s syndrome (pSS) patients, and 106 healthy controls (HCs).White blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IgM, IgG, C3, C4, RF, ANA, dsDNA, Sm, AnuA, aCL, anti-SSA, and anti-SSB were measured by standard laboratory techniques. SLE Disease Activity Index (SLEDAI) was evaluated accordingly. Anti-tubulin-α-1C antibody levels were significantly increased in SLE patients. Elevated anti-tubulin-α-1C were correlated with higher levels of SLEDAI, increased titers of anti-Sm antibody, and decreased titers of anti-dsDNA antibody and significantly associated with cutaneous and mucosal vasculitis and milder renal involvement. Anti-tubulin-α-1C may become a novel biomarker indicative of active vasculitis in SLE and could be applied in future clinical practice.     

Evaluating the diagnostic and prognostic value of lone anti-Sm for autoimmune diseases using Euroimmun line immunoassays

To investigate the value of lone anti-Smith antibody (anti-Sm) using Euroimmun line immunoassay (LIA) in a Chinese population. One thousand two hundred eight of 39,766 patients who were analyzed for anti-Sm had positive anti-Sm, and were divided into true group (having both positive Sm and nRNP/Sm bands) and lone group (only having Sm band without nRNP/Sm band). The proportions of clinical diagnosis of autoimmune diseases (AIDs), non-autoimmune diseases (NAIDs), concentration of C3, C4, and rheumatoid factor (RF), positive rate of autoantibodies of antinuclear antibody (ANA) profile, and titer of anti-Sm and ANA in systemic lupus erythematosus (SLE) patients were analyzed. Lone anti-Sm was evident in 271/1208 (22.42%) of all positive cases. One hundred seventy-five of them had definitive diagnoses with AIDs being the most prominent (69.71%, 122/175). Compared to the true group, SLE patients in the lone group showed significantly lower ANA and anti-Sm titers (both P?<?0.001). There was no difference in frequency of other autoantibodies or C3, C4, and RF levels of SLE patients between the two groups. In NAIDs patients, lone anti-Sm indicates less incidence of kidney injury than true anti-Sm (P?=?0.05). Lone anti-Sm has great diagnostic value in AIDs, especially SLE. Lone anti-Sm has relationship with mild kidney impairment. Positive anti-Sm patients with no clinical findings or SLE diagnosis should be submitted to new testing to identify changes in anti-Sm, because turning of lone anti-Sm to true anti-Sm indicates evolving kidney injury.     

Infliximab-induced autoantibodies: a multicenter study

The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p?=?0.001). Among patients that had ANA before treatment (n?=?92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p?=?0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was discontinued. Infliximab induced the formation of autoantibodies in the combined population (ANA and anti-dsDNA with no apparent clinical importance).     

抗细胞膜DNA抗体对系统性红斑狼疮的诊断价值及与其他抗体联合检测的意义

目的 探讨抗细胞膜DNA(mDNA)抗体在系统性红斑狼疮(SLE)患者的表达以及该特异性抗体对SLE患者的诊断价值及与其他抗体联合检测的意义.方法 用间接免疫荧光法观察培养的HL60细胞的特异性细胞膜的荧光图形,以细胞周连续的环状荧光为抗mDNA抗体阳性.同时检测SLE的其他常见抗体,采用pearsonχ~2检验进行统计学处理.结果 抗mDNA抗体在205例SLE患者中有145例阳性,阳性率70.7%,在55例类风湿关节炎(RA)患者中5例阳性,阳性率为9.1%,45例原发性干燥综合征(pSS)患者中10例阳性,阳性率为22.2%,35例皮肌炎/多肌炎(PM/DM)患者中4例阳性,阳性率14.3%,50名健康对照组中均为阴性.抗mDNA抗体对SLE诊断的敏感性为70.7%,特异性为86.7%.抗mDNA抗体阳性+抗核抗体(ANA)阳性联合检测的敏感性94.6%,特异性76.7%;抗mDNA抗体阳性+抗双链DNA(dsDNA)抗体阳性联合检测的敏感性76.8%,特异性95.5%;抗mDNA抗体阳性+抗Sm抗体阳性联合检测的敏感性79.6%,特异性100%;抗mDNA抗体阳性+抗核小体抗体(AnuA)阳性联合检测的敏感性93.0%,特异性100%.结论 抗mDNA抗体是一种诊断SLE的新的标记抗体,其敏感性较高,特异性强,较抗dsDNA抗体、抗Sm抗体检测更先进.与SLE常用其他抗体联合检测可进一步提高敏感性和特异性.     

Anti-nucleosome antibody: significance in lupus patients lacking anti-double-stranded DNA antibody

OBJECTIVE: To investigate the clinical significance of anti-nucleosome antibodies in SLE patients lacking anti-double stranded DNA (dsDNA) antibodies. METHODS: IgG anti-nucleosome antibodies were detected by enzyme-linked immunosorbent assays (ELISA) in the sera of SLE patients. Anti-dsDNA antibodies were measured by Farr assays and ELISA, not only in the samples taken for anti-nucleosome testing, but also in sera obtained regularly during the follow-up. RESULTS: Ninety-eight (76.0%) out of 129 patients with SLE had anti-nucleosome antibodies. Twenty-five patients (19.4%) consistently showed little or no anti-dsDNA reactivity during the course of their disease, and among these anti-nucleosome antibodies were present in the sera of 15 (60.0%). Of the patients with anti-dsDNA-negative SLE, renal disorders were present in 8 patients (32.0%), all of whom had anti-nucleosome antibodies. Renal disorders were not found in patients (n = 10) who had neither anti-dsDNA nor anti-nucleosome antibodies. Other autoantibodies such as anti-Ro, anti-Sm and anti-cardiolipin were not associated with renal disorders in this group. The levels of anti-nucleosome antibody strongly correlated with the SLEDAI scores, but inversely correlated with serum complement levels in anti-dsDNA negative SLE patients. CONCLUSION: Our data suggest that the anti-nucleosome antibody may be a useful marker for diagnosis and activity assessment of anti-dsDNA negative SLE. Anti-nucleosome antibody may be an important factor for renal involvement in this subgroup of patients.     

Clinico-biological classification of systemic lupus

Anti-nuclear and anti-cytoplasmic antibodies are found in nearly 99% of systemic lupus erythematosus (SLE) patients. Among the different antibodies described, 2 are highly specific for SLE although their frequencies differ considerably. Anti-dsDNA (anti-native DNA) antibodies are detected at some point during disease evolution in 65-95% of the patients, whereas anti-Sm antibodies occur in only 7-30% of the cases, with wide variations according to race and geographical origin. The present study attempts to correlate specific clinical manifestations as a function of certain antibodies: SLE with anti-U1 RNP, with or without anti-dsDNA; SLE with anti-histones; SLE with anti-Ro (SS-A); SLE with anti-phospholipid antibodies or anti-type 5 mitochondrial antibodies; and SLE with anti-ribosomal antibodies. The diversity of these clinical-biological subgroups tends to imply that SLE is a syndrome rather than a distinct disease state.     

抗细胞膜DNA抗体检测方法的建立及对系统性红斑狼疮诊断价值的临床应用研究

目的 应用间接免疫荧光法(IIF)检测抗细胞膜DNA(cmDNA)抗体,探讨抗cmDNA抗体对系统性红斑狼疮(SLE)的诊断价值.比较以人B淋巴细胞株Raji、人早幼粒白血病细胞株HL60为底物,抗cmDNA抗体在SLE中的检测效果.方法 选取306例SLE患者,192例非SLE疾病对照组,包括脊柱关节病(SPA) 52例,类风湿关节炎(RA) 70例,原发干燥综合征(pSS) 30例,其他结缔组织病(CTD)40例.50名健康志愿者作为对照组.采用IIF法观察培养的人B淋巴细胞株Raji、人早幼粒白血病细胞株HL60的细胞膜的荧光图形;用IIF法检测抗核抗体、抗双链DNA(dsDNA)抗体;联合应用免疫双扩散法和蛋白印迹法检测抗Sm抗体,酶联免疫吸附试验(ELISA)法测定抗核小体抗体(AnuA).配对资料比较用McNemarX2检验,相关性分析采用Spearman相关及Logistic回归分析.结果以Raji及HL60 2种细胞株为底物检测SLE患者抗cmDNA抗体,敏感性分别为72.5％、76.1％,特异性分别为91.7％、86.8％,差异均无统计学意义(P＞0.05).抗cmDNA抗体的敏感性明显高于抗Sm抗体及抗dsDNA抗体,差异有统计学意义(P＜0.01);特异性与抗dsDNA抗体相似(P＞0.05),日低于抗Sm抗体及AnuA(P＜0.01).抗cmDNA抗体分别与抗dsDNA抗体、抗Sm抗体及AnuA联合检测在SLE诊断中的敏感性均明显高于上述自身抗体单独检测,差异有统计学意义(P＜0.05).抗cmDNA抗体与SLE患者的黏膜溃疡之间有相关性(OR=2.343,P=0.029).抗cmDNA抗体与红细胞沉降率(ESR)有相关性(OR=1.031,P=0.012).抗cmDNA抗体与SLE疾病活动指数(SLEDAI)评分无相关性(r=0.070,P=0.600).本文研究还证实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.结论 抗cmDNA抗体对SLE诊断的敏感性高,特异性强,可能成为SLE诊断的相对特异性抗体之一.抗cmDNA抗体与抗dsDNA抗体、抗Sm抗体及AnuA联合检测可提高对SLE诊断的敏感性.选择Raji细胞株为底物检测抗cmDNA抗体较HL60细胞株更有优势.     

Clinical and serological features of 35 patients with anti-Ki autoantibodies

The objective of this study was to analyse clinical and serological associations of anti-Ki antibodies. Thirty-five patients with anti-Ki antibodies, detected by CIE, selected from laboratory routine, were studied. All patients were affected by autoimmune diseases: SLE and pSS were the most frequent diagnoses. The cohort was constituted by 27 female and eight males. Main clinical features were skin involvement (60%), xerophtalmia (48.6%), Raynaud's phenomenon (43%), photosensitivity (34%), xerostomia (31.4%). CNS involvement was present in four (11.4%) and renal disease in seven cases (20%). ANA, anti-dsDNA and RF were detected in 100%, 60% and 34.5%. In SLE, anti-Ki was detected in 6% of cases, more frequently in males compared to other SLE patients without anti-Ki (P < 0.004). Nineteen anti-Ki positive patients affected by SLE showed more frequently malar rash and multiple autoantibody specificities compared to 16 anti-Ki positive patients with other diseases (P = 0.044 and P = 0.0003, respectively). Our study confirms a preferential occurrence of anti-Ki antibodies in patients with sicca and skin involvement. Malar rash and multiple ANA specificities were significantly associated with SLE compared to other diseases in our study. Anti-Ki were detected in 6% of patients with SLE with a significant prevalence in males.     

Anti-dsDNA antibodies in sarcoidosis

BACKGROUND: Sarcoidosis is a chronic multisystem disorder characterized by an exaggerated cellular immune response to antigens with the production of various antibodies including rheumatoid factor and antinuclear antibodies (ANA). The prevalence and significance of antibodies to double-stranded DNA (anti-dsDNA) in sarcoid patients is unknown. The occurrence of anti-dsDNA antibodies is known to be a specific marker of systemic lupus erythematosus (SLE). Sarcoidosis can occur with SLE. It is unclear if anti-dsDNA antibodies in patients with sarcoidosis signify the eventual development of SLE. OBJECTIVES: To determine the prevalence of anti-dsDNA antibodies in patients with sarcoidosis in a university hospital and their significance in predicting the diagnosis of associated SLE. METHODS: In a retrospective study, 34 patient files with diagnosed sarcoidosis in a university hospital during a period of 15 years were reviewed for serological markers, including ANA, anti-dsDNA, and immunoglobulin and C3 levels. The occurrence of SLE in these patients also was evaluated. RESULTS: ANA were positive in 10 of 34 of the patients screened. Two patients with sarcoidosis had antibodies to dsDNA. C3 levels in these 34 patients were an average of 87.7 +/- 25.3 mg/100 mL, which is within the normal range. IgG immunoglobulin levels were an average of 2,206 +/- 999 mg/100 mL, which was above normal limits. The 2 patients who were positive for anti-dsDNA had normal C3 levels and SLE did not develop during a follow-up period of 10 to 15 years. CONCLUSIONS: Anti-dsDNA antibodies may occur in patients with sarcoidosis, but their presence does not predict the subsequent development of SLE.     

Demographic,autoimmune, and clinical profiles of patients with systemic lupus erythematosus in Oman

Seventy female and three male Omani systemic lupus erythematosus (SLE) patients are described. At disease onset, 45 (62%) were under 20 years of age, and the remainder were between 20 and 44. Of all cases, 48% were familial. Over 5 years, the cumulative frequencies of autoantibodies was: antinuclear antibodies (ANA) 97%, anti-double-stranded DNA (anti-dsDNA) antibodies 92%, extractable nuclear antigen (ENA) antibodies 64%, antineutrophil cytoplasmic antibodies (ANCA) 58%, antiphospholipid (APL) antibodies 80%, and rheumatoid factor (Rf) 22%. Ribonucleoprotein (RNP) antibodies were found in 15/45 younger-onset and 2/28 older-onset patients (chi(2)=6.63, P<0.02). The mean SLE disease activity score (SLEDAI) was 13.5+11.4, and the cumulative frequencies of systemic involvement were: neurological 33.8%, vascular 10.4%, musculoskeletal 53.9%, renal 50.7%, dermal 80.5%, serosal 23.9%, immunological 95%, constitutional 31.3%, and haematological 26.0%. Linear regression analysis showed that high-titre ANA were predictors for pyuria (odds ratio [OR] 9.06, P=0.01). Antiextractable nuclear antigen antibodies were predictors for disease of the neurological (OR 26.3, P=0.008) and serosal (OR 27.7, P=0.005) systems, and anti-Sm antibodies for alopecia (OR 5.93, P=0.088) and hypocomplementaemia (OR 14.6, P= 0.016). Antibodies of known diagnostic utility may also give insights into the pathogenesis of SLE.     

Circulating anti-double-stranded DNA antibody-secreting cells in patients with systemic lupus erythematosus: a novel biomarker for disease activity

Antibodies against double-stranded DNA (dsDNA) are widely used to diagnose systemic lupus erythematosus (SLE) and evaluate its activity in patients. This study was undertaken to examine the clinical utility of circulating anti-dsDNA antibody-secreting cells for evaluating SLE patients. Anti-dsDNA antibody-secreting cells quantified using an enzyme-linked immunospot assay were detected in the spleen, bone marrow and peripheral blood from MRL/lpr but not in control BALB/c mice. Circulating anti-dsDNA antibody-secreting cells were detected in 29 (22%) of 130 patients with SLE, but in none of 49 with non-SLE connective-tissue disease or 18 healthy controls. The presence of circulating anti-dsDNA antibody-secreting cells was associated with persistent proteinuria, high SLE disease activity index and systemic lupus activity measures, and a high serum anti-dsDNA antibody titre measured with an enzyme-linked immunosorbent assay. The positive predictive value for active disease was 48% for circulating anti-dsDNA antibody-secreting cells versus 17% for serum anti-dsDNA antibodies. A prospective cohort of patients with circulating anti-dsDNA antibodies and inactive SLE showed that the cumulative disease flare-free rate was significantly lower in patients with than without circulating anti-dsDNA antibody-secreting cells (p?相似文献   

Utility of anti-Sm,anti-RNP,anti–Ro/SS-A,and anti–La/SS-B (extractable nuclear antigens) detected by enzyme-linked immunosorbent assay for the diagnosis of systemic lupus erythematosus

Objective. To determine the utility of anti-extractable nuclear antigen (anti-ENA) antibodies detected by enzyme-linked immunosorbent assay as a predictor for the diagnosis of systemic lupus erythematosus (SLE). Methods. Among 2,185 serum samples sent for testing for antinuclear antibodies (ANA) by indirect immunofluorescence, 259 consecutive patients with positive ANA were identified. Medical charts of these patients were reviewed to assess the clinical diagnosis, with the reviewer having no knowledge of the anti-ENA result. Clinical data were abstracted for all patients, and diagnoses established using American College of Rheumatology criteria. The utility of ENA antibodies in the diagnosis of SLE was determined by univariate and multivariate analysis among all patients who were positive for ANA, patients who were positive for ANA and for anti-double-stranded DNA (anti-dsDNA), and patients who were positive for ANA and negative for anti-dsDNA. Clinical differences between SLE patients with and those without anti-ENA antibodies were assessed. Results. Anti-ENA antibodies, especially anti-Ro/SS-A, showed strong predictive diagnostic value among ANA+/anti-dsDNA– patients, but were of no utility among ANA+/anti-dsDNA+ patients. The only clinical manifestations that were more common among anti-ENA+ SLE patients were pleuritis and the use of hydroxychloroquine. Conclusion. The presence of anti-ENA antibodies, especially anti-Ro/SS-A, is a useful predictor for the diagnosis of SLE, primarily among patients attending a referral rheumatology center who are positive for ANA and negative for anti-dsDNA. No major clinical differences were noted among ANA+ SLE patients with versus those without ENA.     

Antinuclear autoantibodies in uveitis

We have studied 44 sera of patients with uveitis, and controls for the presence of ANF and other antinuclear antibodies (ss-DNA, ds-DNA, Poly (I), Poly (G), RNP, Sm, histones) and for the presence of a common anti-DNA idiotype (16/6 Id) employing the ELISA method. Various incidences of antinuclear antibodies were found in sera of patients with uveitis. The uveitis specimens were found to have high titers of autoantibodies to ss-DNA, ds-DNA, Poly (I), histones and Poly (G). High titers of anti-Sm antibodies were detected only in 9% of the uveitis patients, which is markedly lower than the reported percentage of anti-Sm antibodies in SLE. No significant differences were found in the incidence of antinuclear antibodies between sera of patients with localized uveitis and uveitis concomitant with a systemic disorder. Similarly, no relationship was found between location of uveitis (anterior versus posterior) and autoantibody profile. Our results imply that despite considering uveitis as a specific organ malady, it should be regarded serologically as an autoimmune condition.     

Autoantibodies and self-reported health complaints in relatives of systemic lupus erythematosus patients: a community based approach

First-degree relatives (FDRs) and spouses to a population-derived cohort of lupus patients were investigated for the occurrence of selected autoantibodies and self-reported health complaints. A healthy reference population was included. The lupus population consisted of 103 index cases. A total of 275/375 available relatives accepted to enter the study. Two hundred and twenty-six/315 (72%) were FDRs and 49/60 (82%) were spouses. Serum was analysed for ANA using indirect immunofluorescence on Hep-2 cells at the following dilutions: 1:40, 1:80 and 1:160 and in addition sera were tested for anti-dsDNA, IgM RF, ACA (IgM, IgG), anti-beta2GPI (IgM, IgG) and antibodies to prothrombin. ANA positivity occurred more frequently in FDRs compared with spouses and controls at serum dilution 1:160 (10 versus 0% and 2.5%, respectively, P = 0.04 and P < 0.01), 1:80 (24 versus 4% and 5%, respectively, P = 0.003 and P < 0.001) and 1:40 (31 versus 10% and 10%, respectively, P = 0.006 and P < 0.0001). ANA positivity in FDRs occurred randomly, irrespective of family relationship. Fifty-three/184 versus 2/32 FDRs to patients with definite SLE (D-SLE) and incomplete SLE (I-SLE), respectively, tested ANA positive at 1:80 (P < 0.05). FDRs with ANA titer at 80 were affiliated to lupus probands with high SLICC scores (P < 0.05). Self-reported health complaints, cardiovascular/thromboembolic events in particular, were more frequent among FDRs than in spouses. The population-based approach adopted in the present study supports previous clinic-based evidence of an increased propensity for autoantibody occurrence in relatives to SLE patients. In FDRs, present ANA positivity was associated with increased prevalence of health complaints and ANA positivity in FDRs was related to the criterial burden and cumulated damage in corresponding lupus probands. The low ANA frequency among spouses of SLE patients argues against a significant autoantibody triggering effect of shared environment in adult life.     

Association of alpha-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis

OBJECTIVE: Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with alpha-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity. METHODS: One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-alpha-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity. RESULTS: Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-alpha-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-alpha-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-alpha-actinin antibodies (P < 0.01). In patients with GN, anti-alpha-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with alpha-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA. CONCLUSION: The alpha-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.     

Presence of systemic autoimmune disorders in patients with autoimmune thyroid diseases

Methods: 168 consecutive patients with ATD with positive antithyroid antibodies and 75 healthy subjects were tested for the presence of ANA. ANA positive patients were further evaluated by complete history, physical examination, blood and urine tests, and immunological studies. Patients with subjective xerophthalmia and xerostomia were examined by objective tests. Results: 58/168 (35%) patients with ATD were ANA positive compared with 7/75 (9%) healthy controls (p = 0.001). Of 58 ANA positive patients, 6 (10%) had anti-Ro antibodies, 1 had anti-Ro and anti-La antibodies, 7 (12%) had anti-dsDNA antibodies, and 7 (12%) had medium levels of IgG and/or IgM anticardiolipin antibodies (aCL). No healthy subjects had positive anti-dsDNA, antibodies against the extractable nuclear antigens, or aCL. 5/58 (9%) patients fulfilled the criteria for Sjögren''s syndrome (SS). Two patients had features related to systemic lupus erythematosus. No healthy subjects had clinical or laboratory characteristics of systemic autoimmune disorders. Conclusion: ANA are detected in 1/3 of patients with ATD. Anti-dsDNA, anti-Ro, and aCL can also be found in ANA positive patients with ATD. SS occurs in about 1/10 of ANA positive patients with ATD.     

Studies of Filipino patients with systemic lupus erythematosus: autoantibody profile of first-degree relatives

This study surveyed the frequency of autoantibodies among un-affected first-degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients compared with healthy un-related Filipino controls. The sensitivity, specificity and predictive value of the autoantibodies for SLE diagnosis were also assessed in this Filipino cohort. Filipino patients included in the University of Santo Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls included those with no known personal or family history of autoimmune disease. The following autoantibodies were tested in all subjects: anti-nuclear antibody (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti-cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221 healthy controls. Median age of patients was 27 (range 8-66) years with median disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range 5-87) years. Compared with healthy controls, there were significantly more FDRs with positive ANA at titers 1?:?40 to 1?:?160 (p?相似文献   

Information on diagnosis and management of systemic lupus erythematosus derived from the routine measurement of 8 nuclear autoantibodies

OBJECTIVE: To determine the value of routine measurement of a panel of 8 nuclear autoantibodies (ANA/8) for the diagnosis and management of patients with systemic lupus erythematosus (SLE). METHODS: To estimate disease sensitivity of ANA/8, we studied 25 patients with new SLE and 114 with new and established SLE. To estimate disease specificity, 100 patients with other autoimmune rheumatic diseases were included. We used computerized statistical analysis of the level of 8 ANA in relation to clinical activity determined as Systemic Lupus Activity Measure disease activity scores (DAS). Data were collected retrospectively from the charts of 114 patients with 698 visits and evaluated by multiple and piece-wise linear regression analysis (PWLRA) and correlation and cluster analyses. RESULTS: The disease sensitivity of the 3 types of SLE profiles identified was 100% for new SLE patients (n = 25) and 87% for mixed SLE patients; the disease specificity was 98%. Autoantibody levels of anti-ssDNA, dsDNA, and Scl-70 were the best individual correlates of general and organ-specific DAS. Twenty-four percent (R2) of the variability in the general DAS was explained by the multiple regression (R = 0.49), with significant contribution made by anti-Scl-70 (beta = 0.39), dsDNA (beta = 0.17), Sm (beta = 0.10), and SSA (beta = 0.08). PWLRA indicated that for 68% of the 698 clinical presentations (average 6/patient), the observed DAS and the predicted DAS from autoantibody levels were both low and clustered; they were partially discrepant for the remaining 32%, which was explained by the relatively high correlation of DAS with prior changes in autoantibody levels (R = 0.6). The changes in DAS and in anti-dsDNA levels were significantly predicted by the multiple regression at one prior visit, with anti-ssDNA as the main contributor. CONCLUSION: The ANA/8 profile showed ~ 100% sensitivity and ~ 98% specificity for SLE and correlated with contemporary and subsequent changes in DAS and autoantibody levels. Among autoantibodies of this profile, anti-ssDNA (ssDNA) was the most sensitive indicator of SLE and the main contributor to prediction of subsequent changes in DAS.