Jennifer B Soep

Nationwide Children's Hospital, Columbus, Ohio, United States

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Publications (15)64.89 Total impact

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    ABSTRACT: Pulmonary hemorrhage can be classified as either proximal or distal (alveolar). Causes of proximal hemorrhage include infection, foreign body aspiration, pulmonary embolus, trauma, vascular malformation, and pulmonary hypertension. Causes of distal or diffuse alveolar hemorrhage are divided by the histologic presence or absence of capillaritis, which is characterized by inflammation of the alveolar interstitium and pulmonary capillary structure. Pulmonary capillaritis is a rare event in children and is associated with higher morbidity and mortality than diffuse alveolar hemorrhage without capillaritis. This is a report of 17-month-old previously healthy monozygotic twins presenting simultaneously with diffuse alveolar hemorrhage, pulmonary capillaritis, and an otherwise negative serologic workup. This suggests a role of genetic predisposition in this rare disease.
    No preview · Article · Oct 2013 · PEDIATRICS
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    ABSTRACT: Objective Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy. Methods Subgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score ≥4 as post-pubertal or <4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or <110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or <1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models. Results Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures. Conclusions Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy. identifier: NCT00065806.
    No preview · Article · Feb 2013 · Annals of the rheumatic diseases
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    ABSTRACT: Objective: To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥ 1 year post-event in children with arterial ischemic stroke (AIS). Study design: Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Children's Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected. Results: Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02). Conclusion: Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.
    No preview · Article · Dec 2012 · The Journal of pediatrics
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    ABSTRACT: To describe the course and management of thrombotic storm in 8 children. Clinical data were collected and analyzed for consecutive children diagnosed with thrombotic storm, aged 6 months to 21 years inclusive, in the context of a single-institution prospective inception cohort study. Thrombotic storm was defined as newly diagnosed multisite venous thromboembolism (VTE) with acute thrombus progression despite conventional or higher than conventional dosing of heparin or low molecular weight heparin. All evaluations and therapies were ordered by the treating physicians in the context of clinical decision making. Eight of the 178 children with VTE enrolled in the cohort between March 2006 and November 2009 were diagnosed with thrombotic storm. Antiphospholipid antibodies were acutely positive in 6 children, of whom heparin-induced thrombocytopenia was confirmed by serotonin release assay in 2 and atypical in 1. One child died. Five children received a direct thrombin inhibitor, titrated to achieve normalization of markedly elevated D-dimer levels. All children were transitioned to fondaparinux or enoxaparin before receiving extended anticoagulation with warfarin. Immunomodulatory therapy was instituted in all children. During follow-up (median duration, 3 years; range, 2-6 years), 3 of the 7 surviving children experienced recurrent VTE, and 4 children had clinically significant postthrombotic syndrome. Thrombotic storm is an infrequent but potentially fatal presentation of VTE in children. Administration of direct thrombin inhibitors and immune modulation can achieve quiescence, although long-term adverse outcomes are common.
    No preview · Article · May 2012 · The Journal of pediatrics
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    ABSTRACT: Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n=113) or placebo (n=108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). The atorvastatin group achieved lower hsCRP (P=0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups. Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.
    No preview · Article · Jan 2012 · Arthritis & Rheumatology
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    ABSTRACT: Autoimmune polyendocrine syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECD) is a disorder caused by mutations in the autoimmune regulator (AIRE) gene. In some APS-1 patients, significant pulmonary disease is observed. Autoantibodies directed against the potassium channel regulatory protein (KCNRG), found in epithelial cells of terminal bronchioles, have been suggested as a marker for pulmonary disease in APS-1 patients. We report two patients with APS-1; one with and one without lung disease. Patient 1 had multiple admissions for pneumonia and respiratory insufficiency, required non-invasive ventilation, and had findings of bronchiectasis on thoracic imaging and significant lymphocytic infiltrates of the airways on lung biopsy. To verify the autoimmune cause of pulmonary symptoms APS-1 patients, both were tested in a blinded manner for the presence of autoantibodies to KCNRG in serum. We found that only Patient 1 had autoantibodies present. Additionally, Patient 1 had progressive disease despite treatment with several immunomodulating agents, including corticosteroids, azathioprine, and mycophenolate. Patient 1 had a lung biopsy performed which was consistent with B cell lymphocytic aggregates. Rituximab treatment was initiated with apparent good response. This report illustrates the practical use of KCNRG autoantibodies to identify APS-1 patients with pulmonary risk and the successful use of the monoclonal antibody, Rituximab, to treat pulmonary disease in APS-1 patients.
    No preview · Article · Jan 2012 · Pediatric Pulmonology
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    ABSTRACT: To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE). A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches. After an initial Delphi survey (response rate = 70%), a 2-day consensus conference, and 2 followup Delphi surveys (response rates = 63-79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs. CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.
    Full-text · Article · Dec 2011
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    ABSTRACT: Our case series describes three children who were initially diagnosed as having severe pulmonary arterial hypertension (PAH) and subsequently found to be positive for specific autoantibodies suggestive of an underlying autoimmune process. The signs and symptoms of PAH are subtle and may be part of the initial presentation of childhood connective tissue disease (CTD). Evaluation for connective tissue disease in the newly diagnosed pulmonary hypertension (PH) patient is important because early diagnosis of PH as well as CTD is crucial in the successful management of these complex patients. Ongoing monitoring for CTD in patients with severe PAH is warranted.
    Full-text · Article · Mar 2011 · Pediatric Cardiology
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    ABSTRACT: As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.
    No preview · Article · Oct 2010 · Lupus
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    ABSTRACT: We investigated the etiology of acute hepatitis in three children with systemic Juvenile Idiopathic Arthritis (sJIA) taking Interleukin-1 receptor antagonist (IL1RA). Laboratory and clinical data for three children with sJIA diagnosed at ages 13 months to 8 years who developed acute hepatitis during treatment with IL1RA were reviewed for evidence of sJIA flare, infection, macrophage activation syndrome (MAS), malignancy, and drug reaction. In all patients, hepatitis persisted despite cessation of known hepatotoxic drugs and in absence of known infectious triggers, until discontinuation of IL1RA. Liver biopsies had mixed inflammatory infiltrates with associated hepatocellular injury suggestive of an exogenous trigger. At the time of hepatitis, laboratory data and liver biopsies were not characteristic of MAS. In two patients, transaminitis resolved within one week of discontinuing IL1RA, the third improved dramatically in one month. Although sJIA symptoms improved significantly on IL1RA, it appeared that IL1RA contributed to the development of acute hepatitis. Hepatitis possibly occurred as a result of an altered immune response to a typical childhood infection while on IL1RA. Alternatively, hepatitis could have represented an atypical presentation of MAS in patients with sJIA taking IL1RA. Further investigation is warranted to determine how anti-IL1 therapies alter immune responsiveness to exogenous triggers in patients with immune dysfunction such as sJIA. Our patients suggest that close monitoring for hepatic and other toxicities is indicated when treating with IL1RA.
    Full-text · Article · Dec 2009 · Pediatric Rheumatology
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    ABSTRACT: To test the hypothesis that acute elevations of biomarkers of hypercoagulability and inflammation are common in children with arterial ischemic stroke (AIS), particularly among etiologic subtypes that carry an increased risk of recurrent stroke. In this prospective/retrospective institutional-based cohort study of acute childhood-onset AIS (n = 50) conducted between 2005 and 2009, D-dimer, factor VIII (FVIII) activity, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were serially evaluated at the time of clinical blood sampling. Patients were classified by stroke subtype as cardioembolic, moyamoya, non-moyamoya arteriopathy, or other. Both D-dimer and CRP were frequently elevated in acute childhood-onset AIS and exhibited a decreasing trend with time. Acute D-dimer levels were significantly higher in cardioembolic AIS compared with noncardioembolic AIS (median, 2.04 microg/mL [range 0.54-4.54 microg/mL] vs 0.32 microg/mL [0.22-3.18 microg/mL]; P = .002). At an optimal threshold of > or = 0.50 microg/mL, the sensitivity and specificity of D-dimer for cardioembolic subtype were 78% and 79%, respectively. Our findings identify D-dimer and CRP as candidate biomarkers for etiology and prognosis in childhood-onset AIS. Further studies should investigate the role of these and other biomarkers of hypercoagulability and inflammation in childhood-onset AIS.
    No preview · Article · Dec 2009 · The Journal of pediatrics
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    ABSTRACT: To evaluate risk factors for subclinical atherosclerosis in a population of patients with pediatric systemic lupus erythematosus (SLE). In a prospective multicenter study, a cohort of 221 patients underwent baseline measurements of carotid intima-media thickness (CIMT) as part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE disease measures, medications, and traditional risk factors for atherosclerosis were assessed. A standardized protocol was used to assess the thickness of the bilateral common carotid arteries and the mean maximal IMT of 12 segments. Univariable analysis identified potential associations with CIMT, which were examined in multivariable linear regression modeling. Based on the mean-mean common or the mean-max CIMT as the dependent variable, univariable analysis showed significant associations of the following variables with increased CIMT: increasing age, longer SLE duration, minority status, higher body mass index (BMI), male sex, increased creatinine clearance, higher lipoprotein(a) level, proteinuria, azathioprine treatment, and prednisone dose. In multivariable modeling, both azathioprine use (P=0.005 for the mean-mean model and P=0.102 for the mean-max model) and male sex (P<0.001) were associated with increases in the mean-max CIMT. A moderate dosage of prednisone (0.15-0.4 mg/kg/day) was associated with decreases in the mean-max CIMT (P=0.024), while high-dose and low-dose prednisone were associated with increases in the mean-mean common CIMT (P=0.021) and the mean-max CIMT (P=0.064), respectively. BMI (P<0.001) and creatinine clearance (P=0.031) remained associated with increased mean-mean common CIMT, while increasing age (P<0.001) and increasing lipoprotein(a) level (P=0.005) were associated with increased mean-max CIMT. Traditional as well as nontraditional risk factors were associated with increased CIMT in this cohort of patients in the APPLE trial. Azathioprine treatment was associated with increased CIMT. The relationship between CIMT and prednisone dose may not be linear.
    Full-text · Article · May 2009 · Arthritis & Rheumatology
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    ABSTRACT: Poor outcomes in systemic juvenile arthritis have been associated with persistent thrombocytosis, increased sedimentation rates, anemia, polyarthritis, and prolonged steroid use. Off-label treatment with recombinant interleukin-1 receptor antagonist therapy (anakinra) has become more common since reports of its association with reduced systemic symptoms and arthritis scores, improved laboratory parameters of inflammation, and decreased corticosteroid requirements. To examine the efficacy and safety of anakinra in a regional cohort of systemic juvenile arthritis patients. We performed a retrospective case series of systemic juvenile arthritis patients (n = 33) treated with anakinra at 3 Pediatric Rheumatology centers. The effect of anakinra on corticosteroid dose, sedimentation rate, platelet count, albumin, hemoglobin, arthritis joint counts, and height Z score was determined using the paired t test. We evaluated differences in change in these variables between patient groups within the sample determined by: age of onset, anakinra dose, and duration from diagnosis until anakinra treatment. Treatment was associated with decreases in corticosteroid dosage and sedimentation rate and increases in hemoglobin and albumin (P < 0.02). There were decreases in large joint arthritis counts (P < 0.04) but not small joint counts after 3 to 4 months. There were greater decreases in sedimentation rates from pre to post (1-2 months) in patients on high versus low dose anakinra (P < 0.001). Fever and rash, present in 7 cases before treatment, was resolved. Eight patients had periods of arthritis, 1 developed macrophage activation syndrome, and another Epstein Barr virus. Over half of patients reported localized pain or swelling at their injection site. Treatment with anakinra was associated with short-term improvements in large joint counts and laboratory parameters of active disease. Higher anakinra doses may be more efficacious in treating the systemic inflammatory response in systemic onset juvenile idiopathic arthritis patients. A subset of patients had periods of arthritis during treatment, and local side-effects were frequent. Our experience supports the continued use of interleukin-1 inhibition in systemic juvenile arthritis and the search for more effective and more tolerable forms of interleukin-1 inhibition.
    No preview · Article · Apr 2009 · Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases
  • Tamara D Simon · Jennifer B Soep · J Roger Hollister
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    ABSTRACT: Pernio, or chilblains, is a localized inflammatory lesion of the skin resulting from an abnormal response to cold. Five cases were seen among adolescent female patients who presented to our rheumatology service in a pediatric tertiary care center in the winter of 2003 to 2004. All 5 patients were thin (BMI of <25th percentile) and had either toes or fingers that were affected. For each, laboratory evaluation results were unremarkable, including negative antinuclear antibody profile results. Symptomatic treatment, with or without medication, was recommended. Pernio most commonly occurs among young women but may occur among older individuals or among children. Because pernio develops among susceptible individuals who are exposed to nonfreezing cold, the lesions usually begin in the fall or winter and disappear in the spring or early summer. Acute pernio may develop 12 to 24 hours after exposure to the cold. Single or multiple erythematous, purplish, edematous lesions appear, accompanied by intense pain, itching, or burning. Chronic pernio occurs with repeated exposure to the cold and the persistence of lesions. In an acute exacerbation, the major differential diagnosis alternative would be Raynaud's phenomenon, which consists of sharply demarcated cutaneous pallor and cyanosis, followed by erythema, of far shorter duration (hours rather than days). Frostbite is freezing of tissue, with resultant tissue necrosis. Several conditions have been described as predisposing subjects to pernio, including the presence of cryoproteins, excessive cold exposure, and anorexia nervosa among children and systemic lupus erythematosus and antiphospholipid antibodies among adults. It is important, therefore, when evaluating a patient with pernio, both to exclude an underlying diagnosis and to determine whether additional testing is necessary. The lesions of acute pernio are usually self-limited but may lead to recurrent disease. The involved limb should be cleaned and dried, and rewarming should occur. Prevention is the best form of therapy, and cold exposure should be minimized after an initial insult. The prognosis for properly treated pernio is excellent. Nifedipine, which produces vasodilation, has been demonstrated to be effective in reducing pain, facilitating healing, and preventing new lesions of pernio. We think that the 5 cases seen in our rheumatology clinic represent an increase, compared with prior years; the dermatology clinic at the University of Colorado reported a series of 8 children treated during a 10-year period. The reasons for the possible increase are likely multifactorial, with cold climate, a vulnerable population with thin body habitus, and cold exposure all being contributing causes. Of note, the quality of cold in Colorado is quite dry; however, the winter of 2003 to 2004 was not particularly colder or drier than prior years. All patients were very thin, and thin body habitus may be associated with increased cutaneous vasoreactivity. It is also unclear how these cases of pernio may reflect that winter's fashion trends (2 patients reported wearing sandals in winter). General pediatricians, particularly those who practice in colder climates, should be aware of the presentation and treatment of pernio in childhood.
    No preview · Article · Oct 2005 · PEDIATRICS
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    ABSTRACT: To characterize atherosclerotic risk factors and endothelial function in pediatric-onset systemic lupus erythematosus (SLE). Lipoproteins, oxidized state, and autoantibodies to oxidized low-density lipoprotein (Ox-LDL) were assessed. Endothelial function was evaluated using brachial artery reactivity. Thirty-three SLE patients and 30 controls were studied. SLE subjects had significantly decreased mean high-density lipoprotein (HDL) cholesterol (41 mg/dl versus 51 mg/dl; P = 0.002) and apolipoprotein A-I (97 mg/dl versus 199 mg/dl; P = 0.0004). There was no difference between groups in markers of oxidized state (including nitric oxide metabolites, isoprostanes, and Ox-LDL) or in endothelial function. However, SLE subjects had increased median anti-Ox-LDL IgG (2,480 relative light units [RLU] versus 1,567 RLU; P = 0.0007) and IgG immune complexes with LDL (4,222 RLU versus 2,868 RLU; P = 0.002). Pediatric SLE patients had significantly decreased levels of HDL cholesterol and apolipoprotein A-I and elevated titers of autoantibodies to Ox-LDL. Despite these atherosclerotic risk factors, SLE patients had normal measures of oxidized state and endothelial function.
    Preview · Article · Jun 2004 · Arthritis & Rheumatology

Publication Stats

382 Citations
64.89 Total Impact Points


  • 2013
    • Nationwide Children's Hospital
      Columbus, Ohio, United States
  • 2009-2013
    • University of Colorado
      • Department of Pediatrics
      Denver, Colorado, United States
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 2009-2012
    • Children's Hospital Colorado
      Aurora, Colorado, United States
  • 2004
    • University of Colorado Hospital
      Denver, Colorado, United States