BACKGROUND & AIMS: The expression and localization of hepatocyte growth factor/scatter factor (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions retrieved by directional coronary atherectomy and compared with the localization of transforming growth factor beta isoforms (TGF-beta 1, -beta 2, and -beta 3). In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and 0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel, respectively. Immunoreactivity for HGF was much weaker than that for TGF-beta isoforms in these components except in thrombotic tissue. These cells exhibiting strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly demonstrated HGF-IR. In contrast, in control coronary arteries obtained at autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that HGF produced by macrophages play a part in the process of coronary plaque formation attributable to thrombus in man.

背景与目标： 通过免疫组织化学检查了通过定向冠状动脉粥样斑块切除术检索的59例人冠状动脉病变中肝细胞生长因子/散射因子 (HGF/SF) 的表达和定位，并将其与转化生长因子 β 亚型 (tgf-β1，-β2和-β3) 的定位进行了比较。在59个标本中的21个 (35.6%) 中，HGF样免疫反应性 (hgf-ir) 被揭示。血栓组织中45% (14/31) 的HGF免疫阳性率显着 (P < 0.05) 高于纤维组织，新内膜增生和动脉粥样硬化稀粥中的7.3% (4/55)，7.1% (3/42) 和0% (0/14)。分别。除血栓形成组织外，这些成分中HGF的免疫反应性比TGF-β 同工型的免疫反应性弱得多。这些表现出强hgf-ir的细胞是炎性细胞，例如血栓形成组织中，与血栓相邻的组织病变以及部分新生血管病变的毛细血管壁外部的单核细胞/巨噬细胞。平滑肌细胞 (smc) 几乎不显示HGF-IR。相反，在尸检获得的对照冠状动脉中，hgf-ir在smc中强烈表达。这些发现表明，巨噬细胞产生的HGF在人类血栓形成引起的冠状动脉斑块形成过程中发挥了作用。

BACKGROUND & AIMS: BACKGROUND:A few prospective controlled trials comparing early functional rehabilitation after Achilles tendon repair and non-operative immobilization have been reported. HYPOTHESES:There is no difference in Achilles tendon elongation between early motion and immobilization after Achilles tendon repair. Tendon elongation does not correlate with the clinical outcome. STUDY DESIGN:Randomized clinical trial; Level of evidence, 2. METHODS:Fifty patients with acute Achilles tendon rupture were randomized postoperatively to receive either early movement of the ankle between neutral and plantar flexion in a brace for 6 weeks or immobilization in tension using a below-knee cast with the ankle in a neutral position for 6 weeks. Full weightbearing was allowed after 3 weeks in both groups. Standardized radiographs to measure previously placed radiographic markers were taken on the first day postoperatively and at 1, 3, 6, 12, 24 weeks postoperatively, with the final radiograph a mean of 60 (SD, 6.4) weeks postoperatively. The outcome was assessed at the 3-month and final checkups by the clinical scoring method described by Leppilahti et al and included subjective factors and objective factors. RESULTS:Tendon elongation occurred in both groups but was somewhat less in the early motion group (median 2 mm in the early motion group vs median 5 mm in the cast group a mean of 60 weeks postoperatively, P = .054). The elongation curves first rose and then slowly fell in both groups. The patients who had less elongation achieved a better clinical outcome (rho = -.42, P = .017). Tendon elongation did not correlate significantly with age, body mass index, or isokinetic peak torques. CONCLUSION:Achilles tendon elongation was somewhat less in the early motion group and correlated with the clinical outcome scores. We recommend early functional postoperative treatment after Achilles rupture repair.

背景与目标：

BACKGROUND & AIMS: BACKGROUND AND PURPOSE:Imaging of bisphosphonate-induced osteonecrosis of the jaw is essential for surgical planning. We compared the extent of BONJ on contrast-enhanced MR imaging, [(18)F] fluoride PET/CT, and panoramic views derived from standard conebeam CT with clinical pre- and intraoperative examinations. MATERIALS AND METHODS:Between February 2011 and January 2012, ten subjects with written informed consent (9 women; mean, 69.6 years; range, 53-88 years) were included in this prospective ethics-board-approved study. Patients underwent CEMR imaging, [(18)F] fluoride PET/CT, and CBCT and were clinically examined pre- and intraoperatively. Surgery was performed, and BONJ was histologically confirmed in 9 patients. Location and extent of BONJ on different modalities/examinations were graphically compared (0 = no pathologic finding, 1 = smallest, 5 = largest extent of BONJ). Rank tests were used to assess overall and paired differences of ratings in 9 patients. A P value <.05 was considered statistically significant. RESULTS:Significant differences in BONJ extent among different modalities and examinations were found (P < .001). The highest median rank was seen in PET/CT (4 ± 1.12) and CEMR imaging (4 ± 1.01), followed by intraoperative examinations (3 ± 0.71), CBCT (2 ± 0.33), and preoperative examinations (1 ± 0). No significant differences were found between PET/CT and CEMR imaging (P = .23), except when comparing PET/CT to either CBCT, pre- and intraoperative examinations (all P < .05). Preoperative examinations showed significantly less extensive disease than all other modalities/examinations (all P < .05). CONCLUSIONS:[(18)F] fluoride PET/CT and CEMR imaging revealed more extensive involvement of BONJ compared with panoramic views from CBCT and clinical examinations.

背景与目标：

BACKGROUND & AIMS: :The accurate design of new protein-protein interactions is a longstanding goal of computational protein design. However, most computationally designed interfaces fail to form experimentally. This investigation compares five previously described successful de novo interface designs with 158 failures. Both sets of proteins were designed with the molecular modeling program Rosetta. Designs were considered a success if a high-resolution crystal structure of the complex closely matched the design model and the equilibrium dissociation constant for binding was less than 10 μM. The successes and failures represent a wide variety of interface types and design goals including heterodimers, homodimers, peptide-protein interactions, one-sided designs (i.e., where only one of the proteins was mutated) and two-sided designs. The most striking feature of the successful designs is that they have fewer polar atoms at their interfaces than many of the failed designs. Designs that attempted to create extensive sets of interface-spanning hydrogen bonds resulted in no detectable binding. In contrast, polar atoms make up more than 40% of the interface area of many natural dimers, and native interfaces often contain extensive hydrogen bonding networks. These results suggest that Rosetta may not be accurately balancing hydrogen bonding and electrostatic energies against desolvation penalties and that design processes may not include sufficient sampling to identify side chains in preordered conformations that can fully satisfy the hydrogen bonding potential of the interface.

背景与目标： : 精确设计新的蛋白质-蛋白质相互作用是计算蛋白质设计的长期目标。但是，大多数计算设计的接口都无法通过实验形成。该调查比较了五个先前描述的成功的从头接口设计和158故障。两组蛋白质都是使用分子建模程序Rosetta设计的。如果配合物的高分辨率晶体结构与设计模型紧密匹配并且结合的平衡解离常数小于10μm，则认为设计是成功的。成功和失败代表了各种各样的界面类型和设计目标，包括异二聚体，同二聚体，肽-蛋白质相互作用，单面设计 (即仅其中一种蛋白质发生突变) 和双面设计。成功设计的最显着特征是，与许多失败的设计相比，它们在界面上的极性原子更少。试图创建广泛的跨界面氢键集的设计导致无法检测到结合。相反，极性原子占许多天然二聚体的界面面积的40% 以上，并且天然界面通常包含广泛的氢键网络。这些结果表明，Rosetta可能无法准确地平衡氢键和静电能免受去溶剂化的影响，并且设计过程可能不包括足够的采样来识别可以完全满足界面氢键电势的预定构象中的侧链。

BACKGROUND & AIMS: OBJECTIVES:There are no direct comparisons of blood glucose values in samples collected with barrier serum tubes (SST) and NaF/potassium oxalate (NaF/KOx) plasma tubes. Collection of samples in SST tubes can offer considerable savings and specimen processing advantages for national level surveys. DESIGN AND METHODS:Serum and plasma samples were collected under 'field conditions' from a single draw of 3692 individuals participating in the Canadian Health Measures Survey. The samples were analyzed retrospectively using the VITROS GLU Slide method (glucose oxidase-based). RESULTS:There was a high rate of hemolysis in the NaF/KOx tubes (86.2%) while hemolysis was infrequently observed with the SST tubes (2%). Comparing only blood draws where no hemolysis was observed in both tubes (n=495; paired t-test) showed no effect of tube type on serum/plasma glucose concentrations. This was also observed when data was restricted to cases when only SST samples were not hemolyzed (n=3546; paired t-test). CONCLUSIONS:These data show that both collection tubes can be used under survey collection and processing conditions to measure glucose with our assay system with no difference in reported results.

背景与目标：

BACKGROUND & AIMS: :Accurate muscle geometry (muscle length and moment arm) is required to estimate muscle function when using musculoskeletal modelling. In shoulder, muscles are often modelled as a collection of independent line segments, leading to non-physiological muscles trajectory, especially for the rotator cuff muscles. To prevent this, a surface mesh model was developed and validated against 7 MRI positions in one participant. Mean moment arm errors was 11.4% for the line vs. 8.8% for the mesh model. While the model with independent lines led to some non-physiological trajectories, the mesh model gave lower misestimations of muscle lengths and moment arms.

背景与目标： : 使用肌肉骨骼模型时，需要准确的肌肉几何形状 (肌肉长度和力矩臂) 来估计肌肉功能。在肩部，肌肉通常被建模为独立线段的集合，从而导致非生理肌肉轨迹，尤其是对于肩袖肌肉。为了防止这种情况，开发了一个表面网格模型，并针对一名参与者的7个MRI位置进行了验证。11.4% 直线的平均力矩臂误差与网格模型的8.8%。虽然具有独立线条的模型导致了一些非生理轨迹，但网格模型对肌肉长度和力矩臂的误判较低。

BACKGROUND & AIMS: PURPOSE:The purpose of this article was to investigate the accuracy of the WISC-IV short forms in estimating Full Scale Intelligence Quotient (FSIQ) and General Ability Index (GAI) in pediatric epilepsy. METHODS:One hundred and four children with epilepsy completed the WISC-IV as part of a neuropsychological assessment at a tertiary-level children's hospital. The clinical accuracy of eight short forms was assessed in two ways: (a) accuracy within +/- 5 index points of FSIQ and (b) the clinical classification rate according to Wechsler conventions. The sample was further subdivided into low FSIQ (≤ 80) and high FSIQ (> 80). RESULTS:All short forms were significantly correlated with FSIQ. Seven-subtest (Crawford et al. [2010] FSIQ) and 5-subtest (BdSiCdVcLn) short forms yielded the highest clinical accuracy rates (77%-89%). Overall, a 2-subtest (VcMr) short form yielded the lowest clinical classification rates for FSIQ (35%-63%). The short form yielding the most accurate estimate of GAI was VcSiMrBd (73%-84%). CONCLUSIONS:Short forms show promise as useful estimates. The 7-subtest (Crawford et al., 2010) and 5-subtest (BdSiVcLnCd) short forms yielded the most accurate estimates of FSIQ. VcSiMrBd yielded the most accurate estimate of GAI. Clinical recommendations are provided for use of short forms in pediatric epilepsy.

背景与目标：

BACKGROUND & AIMS: AIM:The aim of this study was to determine the relationship between parent and child Full-scale IQ (FSIQ) in children with epilepsy and in typically developing comparison children and to examine parent-child IQ differences by epilepsy characteristics. METHOD:The study participants were 97 children (50 males, 47 females; age range 8-18y; mean age 12y 3mo, SD 3y1mo) with recent-onset epilepsy including idiopathic generalized (n=43) and idiopathic localization-related epilepsies (n=54); 69 healthy comparison children (38 females, 31 males; age range 8-18y; mean age 12y 8mo, SD 3y 2mo), and one biological parent per child. All participants were administered the Wechsler Abbreviated Scale of Intelligence (WASI). FSIQ was compared in children with epilepsy and typically developing children; FSIQ was compared in the parents of typically developing children and the parents of participants with epilepsy; parent-child FSIQ differences were compared between the groups. RESULTS:FSIQ was lower in children with epilepsy than in comparison children (p<0.001). FSIQ of parents of children with epilepsy did not differ from the FSIQ of the parents of typically developing children. Children with epilepsy had significantly lower FSIQ than their parents (p<0.001), whereas comparison children did not. The parent-child IQ difference was significantly higher in the group with epilepsy than the comparison group (p=0.043). Epilepsy characteristics were not related to parent-child IQ difference. INTERPRETATION:Parent-child IQ difference appears to be a marker of epilepsy impact independent of familial IQ, epilepsy syndrome, and clinical seizure features. This marker is evident early in the course of idiopathic epilepsies and can be tracked over time.

背景与目标：

BACKGROUND & AIMS: INTRODUCTION:Fatigue after treatment for breast cancer (BC) is common, but poorly understood. We examined the fatigue levels during first year after radiotherapy (RT) according to the extent of RT (local or locoregional), hormonal therapy (HT) and chemotherapy (CT). The impact of comorbidity was also explored. Moreover, we compared fatigue levels in patients with the general population (GenPop) data. MATERIAL AND METHODS:BC patients (n = 250) referred for post-operative RT at St. Olavs Hospital, Trondheim, Norway, were enrolled. Fatigue was measured by the EORTC QLQ-C30-fatigue subscale, ranging from 0 to 100, before RT (baseline), after RT, and at three, six, and 12 months. Clinical and treatment-related factors were recorded at baseline. GenPop data was available from a previous survey (n = 652). Linear mixed models and analysis of covariance were applied. RESULTS:Compliance ranged from 87% to 98%. At baseline, mean value (SD) of fatigue in BC patients was 26.8 (23.4). The level increased during RT (mean change 8.3, 95% CI 5.5-11.1), but declined thereafter and did not differ significantly from pre-treatment levels at subsequent time points. In age-adjusted analyses, locoregional RT accounted for more overall fatigue than local RT (mean difference 6.6, 95% CI 1.2-12.0), but the association was weakened and not statistical significant when adjusting for CT and HT. Similar pattern was seen for CT and HT. The course of fatigue differed significantly by CT (p < 0.001, interaction test). At baseline, fatigue levels were higher in patients with than without CT, but at subsequent time points similar levels were evident, indicating a temporary adverse effect of CT. Comorbidity was significantly associated with increased level of fatigue, independent of other factors (mean difference 8.1, 95% CI 2.2-14.1). BC-patients were not significantly more fatigued than GenPop, except for immediately after ending RT, and then only among those without comorbidity (mean 35.9 vs. 25.8, p < 0.001). CONCLUSION:Comorbidity seems to be a more important determinant for fatigue levels than the cancer treatment.

背景与目标：

BACKGROUND & AIMS: :Type 2 diabetes is a strong risk factor for stroke. Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor in clinical use against type 2 diabetes. The aim of this study was to determine the potential antistroke efficacy of linagliptin in type 2 diabetic mice. To understand whether efficacy was mediated by glycemia regulation, a comparison with the sulfonylurea glimepiride was done. To determine whether linagliptin-mediated efficacy was dependent on a diabetic background, experiments in nondiabetic mice were performed. Type 2 diabetes was induced by feeding the mice a high-fat diet for 32 weeks. Mice were treated with linagliptin/glimepiride for 7 weeks. Stroke was induced at 4 weeks into the treatment by transient middle cerebral artery occlusion. Blood DPP-4 activity, glucagon-like peptide-1 (GLP-1) levels, glucose, body weight, and food intake were assessed throughout the experiments. Ischemic brain damage was measured by determining stroke volume and by stereologic quantifications of surviving neurons in the striatum/cortex. We show pronounced antistroke efficacy of linagliptin in type 2 diabetic and normal mice, whereas glimepiride proved efficacious against stroke in normal mice only. These results indicate a linagliptin-mediated neuroprotection that is glucose-independent and likely involves GLP-1. The findings may provide an impetus for the development of DPP-4 inhibitors for the prevention and treatment of stroke in diabetic patients.

背景与目标： : 2型糖尿病是中风的重要危险因素。利格列汀是临床抗2型糖尿病的二肽peptidase-4 (DPP-4) 抑制剂。这项研究的目的是确定利格列汀在2型糖尿病小鼠中的潜在抗中风功效。为了了解疗效是否由血糖调节介导，与磺酰脲类格列美脲进行了比较。为了确定利格列汀介导的疗效是否取决于糖尿病背景，在非糖尿病小鼠中进行了实验。通过给小鼠喂食高脂饮食32周而诱发2型糖尿病。用利格列汀/格列美脲治疗小鼠7周。短暂性大脑中动脉闭塞在治疗4周时诱发中风。在整个实验中评估血液DPP-4活性，胰高血糖素样肽-1 (GLP-1) 水平，葡萄糖，体重和食物摄入量。通过确定中风量和纹状体/皮质中存活神经元的立体定量来测量缺血性脑损伤。我们显示了利格列汀在2型糖尿病和正常小鼠中的明显抗中风功效，而格列美脲仅在正常小鼠中被证明对中风有效。这些结果表明利格列汀介导的神经保护作用是不依赖葡萄糖的并且可能涉及GLP-1。这些发现可能为糖尿病患者预防和治疗中风的DPP-4抑制剂的开发提供动力。

BACKGROUND & AIMS: BACKGROUND:Accuracy of bone marrow (BM) blast count in low-risk myelodysplastic syndromes (MDS) still remains a challenge though it is essential for prognosis. We investigated whether the enumeration of CD34+ myeloid cells by flow cytometry immunophenotyping (FCI) could be used as a consistent parameter for clinical MDS studies. METHODS:Six clinical centers entered the study and information on their FCI protocols was recorded. Sixty-seven flow cytometry listmodes from BM samples of patients with low-risk MDS with <5% BM blasts were exchanged among participants in two different rounds. Interlaboratory variations on the quantification of CD34+ myeloid cells were calculated and strategies to solve differences were evaluated. RESULTS:An overall "very good" agreement on CD34+ cell count among participants (intraclass correlation coefficient = 0.720) was observed, but agreement was "low" in 22 files. No single parameter could fully explain all discrepancies, but 3 technical issues were identified as relevant: the use of the CD34/CD45/CD117/HLA-DR mAb combination, acquisition of ≥50,000 events and a low percentage of debris/aggregates. The frequency of discordant results increased with the accumulation of pitfalls (none, 16%; 1 pitfall, 40%; 2 pitfalls, 83%; P = 0.006). Finally, the use of a common gating strategy for analysis increased the percentage of files with "very good" agreement to 100%. CONCLUSIONS:Prevention of specific technical pitfalls is mandatory to reach a good reproducibility of CD34+ cell count among centers. These recommendations set the basis for laboratory standardization and enable the use of CD34+ cell enumeration as additional information in low-risk MDS patients. © 2017 International Clinical Cytometry Society.

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BACKGROUND & AIMS: BACKGROUND:Injectable daxibotulinumtoxinA (RT002) is an investigational botulinum toxin Type A in clinical development. It is formulated with a proprietary peptide and offers the potential of a longer acting neurotoxin therapy. OBJECTIVE:To compare the safety, efficacy, and duration of response of daxibotulinumtoxinA with onabotulinumtoxinA and placebo [www.clinicaltrials.gov NCT02303002]. METHODS:In this Phase 2, randomized, dose-ranging, parallel-group, double-blind, multicenter study, subjects with moderate or severe glabellar lines at maximum frown were randomly assigned to 20U, 40U, or 60U daxibotulinumtoxinA, 20U onabotulinumtoxinA, or placebo. Glabellar line severity was evaluated by investigators and subjects at least every 4 weeks, for at least 24 weeks. RESULTS:Overall, 268 subjects enrolled. Statistical and clinical superiority were observed for 40U and 60U daxibotulinumtoxinA over 20U onabotulinumtoxinA for a range of efficacy outcomes despite the study not being powered to detect statistically significant differences between these active treatment groups. CONCLUSION:The 40U dose of daxibotulinumtoxinA was well tolerated (e.g., absence of ptosis) and had the most favorable risk: benefit profile. Compared with 20U onabotulinumtoxinA, it exhibited a significantly greater response rate and a significantly longer duration of response (median of 24 weeks vs 19 weeks; p = .030).

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:Intranasal corticosteroids (INCs) are the most effective modality for treating allergic rhinitis and their sensory attributes are important in patient compliance. This study aimed to compare the sensory attributes (scent, immediate taste, aftertaste, run down to throat, nose run off, soothing feel, nasal irritation, and urge to sneeze) and immediate response to the new intranasal steroid, ciclesonide (CIC), with fluticasone propionate (FLP) in allergic rhinitis. MATERIALS AND METHODS:A randomized, double blind, single dose, crossover study was done with 74 patients presenting with acute allergic rhinitis. Eligible subjects were randomized in 1:1 ratio to one of the two treatment sequences - CIC followed by FLP or vice versa. Sensory attributes were assessed using a questionnaire to score each item on a seven-point Likert scale, immediately and 2 min after dosing. Total nasal symptom score (TNSS) was calculated to evaluate immediate efficacy 10 min after first drug administration. Overall preference was recorded 10 min after the second drug administration. Patients were queried about treatment emergent adverse events following study drug administration and also 24 h later over the phone. RESULTS:Patients (58% males; pooled median age 32 years [Interquartile range, IQR, 25-41]; pooled median symptom duration 24 months [IQR 12-72]) preferred FLP over CIC nasal spray overall (55.41% vs. 25.68%, P = 0.007) and also with respect to attributes of scent, soothing feel, and nasal irritation. There was no statistically significant difference in immediate efficacy. Two patients reported mild headache following CIC first, while three felt mild headache, one dizziness, and one nasal congestion following FLP first administration. There were no delayed adverse events. CONCLUSIONS:There was no difference in immediate outcome following use of either of the two INCs. FLP was preferred over CIC with respect to scent, soothing feel and nasal irritation, and also overall. There were no significant adverse events.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. METHODS:In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. RESULTS:We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. CONCLUSIONS:We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally, a simulation should be based on real data for adequately reflecting complex observational data structures, such as found in epidemiological cohort studies.

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BACKGROUND & AIMS: OBJECTIVE:Replacement of standard immunofluorescence methods with bead-based assays for antinuclear antibody (ANA) testing is a new clinical option. The aim of this study was to evaluate a large, multiethnic cohort of patients with systemic lupus erythematosus (SLE), blood relatives, and unaffected control individuals for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods. METHODS:Serum samples (1,540 SLE patients, 1,154 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, indirect immunofluorescence (IIF), and immunodiffusion. Autoantibody prevalence, sensitivity for disease detection, clustering of autoantibodies, and associations between newer methods and standard immunodiffusion results were evaluated. RESULTS:The frequencies of ANAs in the sera from African American, Hispanic, and European American patients with SLE were 89%, 73%, and 67%, respectively, by BioPlex 2200 bead-based assay and 94%, 84%, and 86%, respectively, by IIF. When comparing the serum prevalence of 60-kd Ro, La, Sm, nuclear RNP A, and ribosomal P autoantibodies across assays, the sensitivity of detection ranged from 0.92 to 0.83 and the specificity ranged from 0.90 to 0.79. Autoantibody cluster analysis showed associations of autoantibody specificities in 3 subsets: 1) 60 kd Ro, 52-kd Ro, and La, 2) spliceosomal proteins, and 3) double-stranded DNA (dsDNA), chromatin, and ribosomal P. Familial aggregation of Sm/RNP, ribosomal P, and 60-kd Ro in SLE patient sibling pairs was observed (P ≤ 0.004). Simplex-pedigree SLE patients had a greater prevalence of dsDNA (P = 0.0003) and chromatin (P = 0.005) autoantibodies compared to patients with a multiplex SLE pedigree. CONCLUSION:The frequencies of ANAs detected by a bead-based assay are lower than those detected by IIF in European American patients with SLE. These assays have strong positive predictive values across ethnic groups, provide useful information for clinical care, and provide unique insights into familial aggregation and autoantibody clustering.

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