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Journal ArticleDOI

Cluster Analysis of Autoantibodies in 852 Patients with Systemic Lupus Erythematosus from a Single Center

TL;DR: This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibia clusters may be useful in predicting the outcome of the disease.
Abstract: Objective. Associations between autoantibodies and clinical features have been described in systemic lupus erythematosus (SLE). Herein, we aimed to define autoantibody clusters and their clinical correlations in a large cohort of patients with SLE. Methods. We analyzed 852 patients with SLE who attended our clinic. Seven autoantibodies were selected for cluster analysis: anti-DNA, anti-Sm, anti-RNP, anticardiolipin (aCL) immunoglobulin (Ig)G or IgM, lupus anticoagulant (LAC), anti-Ro, and anti-La. Two-step clustering and Kaplan-Meier survival analyses were used. Results. Five clusters were identified. A cluster consisted of patients with only anti-dsDNA antibodies, a cluster of anti-Sm and anti-RNP, a cluster of aCL IgG/M and LAC, and a cluster of anti-Ro and anti-La antibodies. Analysis revealed 1 more cluster that consisted of patients who did not belong to any of the clusters formed by antibodies chosen for cluster analysis. Sm/RNP cluster had significantly higher incidence of pulmonary hypertension and Raynaud phenomenon. DsDNA cluster had the highest incidence of renal involvement. In the aCL/LAC cluster, there were significantly more patients with neuropsychiatric involvement, antiphospholipid syndrome, autoimmune hemolytic anemia, and thrombocytopenia. According to the Systemic Lupus International Collaborating Clinics damage index, the highest frequency of damage was in the aCL/LAC cluster. Comparison of 10 and 20 years survival showed reduced survival in the aCL/LAC cluster. Conclusion. This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibody clusters may be useful in predicting the outcome of the disease. Autoantibody clusters in SLE may exhibit differences according to the clinical setting or population.
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Journal ArticleDOI
TL;DR: The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion, based on emerging new evidence.
Abstract: Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.

1,079 citations

Journal ArticleDOI
TL;DR: The different auto-antibodies reported to be involved in SLE are described and how autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.
Abstract: Systemic Lupus Erythematosus (SLE) is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of different antibody-secreting cell populations are considered highly relevant for the disease pathogenesis. These cells are developed and stimulated through different ways leading to the secretion of a variety of isotypes, affinities and idiotypes. Each of them has a particular mechanism of action binding to a specific antigen and recognized by distinct receptors. The effector responses triggered lead to a chronic tissue inflammation. DsDNA autoantibodies are the most studied as well as the first in being characterized for its pathogenic role in Lupus nephritis. However, others are of growing interest since they have been associated with other organ-specific damage, such as anti-NMDAR antibodies in neuropsychiatric clinical manifestations or anti-β2GP1 antibodies in vascular symptomatology. In this review, we describe the different auto-antibodies reported to be involved in SLE. How autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.

106 citations

Journal ArticleDOI
17 Apr 2017-PLOS ONE
TL;DR: In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis, a more robust measure of atherosclerosis, which demonstrates the importance of careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.
Abstract: Background Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups. Methods 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjogren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls. Results Median age was 49 (IQR 36–59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035). Conclusions In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.

82 citations

Journal ArticleDOI
TL;DR: The other conditions that can result in thrombocytopenia are discussed as they have commonalities with APS and their recognition is important to establish the most appropriate treatment strategy.
Abstract: The association between antiphospholipid antibodies (aPL) and clinical problems goes beyond what is stated in the antiphospholipid syndrome (APS) classification criteria, namely thrombosis and pregnancy morbidity, and thrombocytopenia is the most common non-criteria hematologic manifestation of aPL with a frequency ranging from 20 to 50 %. Thrombocytopenia is rarely severe, and hemorrhage is far less common than thrombosis. However, when anticoagulation is considered, it may constitute a clinical problem with increased bleeding risk. Furthermore, thrombocytopenia represents a risk factor for thrombosis in aPL-positive patients. Therefore, it is important to understand the pathogenesis and the clinical associations of thrombocytopenia to build the right medical approach in aPL-positive patients. In this paper, we review the literature on aPL/APS-associated thrombocytopenia and briefly discuss the other conditions that can result in thrombocytopenia as they have commonalities with APS and their recognition is important to establish the most appropriate treatment strategy.

59 citations


Cites background from "Cluster Analysis of Autoantibodies ..."

  • ...or lupus anticoagulant (LA)) [21] where a significantly high rate of thrombocytopenia (36 %) coexisted with neuropsychiatric manifestations, arterial and/or venous thrombosis, and autoimmune hemolytic anemia....

    [...]

Journal ArticleDOI
TL;DR: In this cohort of SLE patients, anti-Sm antibodies were associated with several clinical features including serious manifestations such as renal, neurologic, and hematologic disorders as well as vasculitis.
Abstract: The aim of this study was to determine the association of anti-Sm antibodies with clinical manifestations, comorbidities, and disease damage in a large multi-ethnic SLE cohort. SLE patients (per American College of Rheumatology criteria), age ≥16 years, disease duration ≤10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal US cohort were studied. Socioeconomic-demographic features, cumulative clinical manifestations, comorbidities, and disease damage (as per the Systemic Lupus International Collaborating Clinics Damage Index [SDI]) were determined. The association of anti-Sm antibodies with clinical features was examined using multivariable logistic regression analyses adjusting for age, gender, ethnicity, disease duration, level of education, health insurance, and smoking. A total of 2322 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.4 (12.8) years and the mean (SD) disease duration was 9.0 (7.9) years; 2127 (91.6 %) were women. Anti-Sm antibodies were present in 579 (24.9 %) patients. In the multivariable analysis, anti-Sm antibodies were significantly associated with serositis, renal involvement, psychosis, vasculitis, Raynaud’s phenomenon, hemolytic anemia, leukopenia, lymphopenia, and arterial hypertension. No significant association was found for damage accrual. In this cohort of SLE patients, anti-Sm antibodies were associated with several clinical features including serious manifestations such as renal, neurologic, and hematologic disorders as well as vasculitis.

57 citations


Cites background from "Cluster Analysis of Autoantibodies ..."

  • ...This observation has been previously reported, especially with the coexistence of anti-ribonucleoprotein (RNP) antibodies [11, 14, 18, 30, 42]....

    [...]

References
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TL;DR: An electrical signal transmission system, applicable to the transmission of signals from trackside hot box detector equipment for railroad locomotives and rolling stock, wherein a basic pulse train is transmitted whereof the pulses are of a selected first amplitude and represent a train axle count.
Abstract: 1. Introduction. 2. Partitioning Around Medoids (Program PAM). 3. Clustering large Applications (Program CLARA). 4. Fuzzy Analysis. 5. Agglomerative Nesting (Program AGNES). 6. Divisive Analysis (Program DIANA). 7. Monothetic Analysis (Program MONA). Appendix 1. Implementation and Structure of the Programs. Appendix 2. Running the Programs. Appendix 3. Adapting the Programs to Your Needs. Appendix 4. The Program CLUSPLOT. References. Author Index. Subject Index.

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TL;DR: This book make understandable the cluster analysis is based notion of starsmodern treatment, which efficiently finds accurate clusters in data and discusses various types of study the user set explicitly but also proposes another.
Abstract: The Wiley-Interscience Paperback Series consists of selected books that have been made more accessible to consumers in an effort to increase In both the increasingly important and distribution we show how these methods. Our experiments demonstrate that together can deal with most applications technometrics. In an appropriate visualization technique is to these new. The well written and efficiently finds accurate clusters in data including. Of applied value for several preprocessing tasks discontinuity preserving smoothing feature clusters! However the model based notion of domain knowledge from real data repositories in data. Discusses various types of study the user set explicitly but also propose another. This book make understandable the cluster analysis is based notion of starsmodern treatment.

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Proceedings ArticleDOI
01 Jun 1996
TL;DR: Balanced Iterative Reducing and Clustering using Hierarchies (BIRCH) as discussed by the authors is a data clustering method that is especially suitable for very large databases.
Abstract: Finding useful patterns in large datasets has attracted considerable interest recently, and one of the most widely studied problems in this area is the identification of clusters, or densely populated regions, in a multi-dimensional dataset. Prior work does not adequately address the problem of large datasets and minimization of I/O costs.This paper presents a data clustering method named BIRCH (Balanced Iterative Reducing and Clustering using Hierarchies), and demonstrates that it is especially suitable for very large databases. BIRCH incrementally and dynamically clusters incoming multi-dimensional metric data points to try to produce the best quality clustering with the available resources (i.e., available memory and time constraints). BIRCH can typically find a good clustering with a single scan of the data, and improve the quality further with a few additional scans. BIRCH is also the first clustering algorithm proposed in the database area to handle "noise" (data points that are not part of the underlying pattern) effectively.We evaluate BIRCH's time/space efficiency, data input order sensitivity, and clustering quality through several experiments. We also present a performance comparisons of BIRCH versus CLARANS, a clustering method proposed recently for large datasets, and show that BIRCH is consistently superior.

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01 Mar 1993-Medicine
TL;DR: The presence of ANA, a high titer of anti-dsDNA, rheumatoid factor, anti-ENA, and antiphospholipid antibodies also distinguished additional homogeneous SLE subsets of clinical significance.

915 citations

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