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1.
Artigo em Inglês | MEDLINE | ID: mdl-31677989

RESUMO

As SLE onset is often in young adulthood, pregnancy is common and is usually successful. Pregnancy, though, is considered high-risk due to a combination of maternal (lupus flare, diabetes, pre-eclampsia) and fetal (miscarriage, intrauterine fetal demise, preterm birth, intrauterine growth restriction, congenital heart block) risks. Pregnancy should be planned for a time of good control of SLE (on allowable medications). The antimalarial hydroxychloroquine should be continued. The only permitted immunosuppressive drugs are azathioprine and tacrolimus. Of the antiphospholipid antibodies, only the lupus anticoagulant has been associated with adverse pregnancy outcomes in the largest prospective multicenter study, Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE). Management of antiphospholipid syndrome in pregnancy is low molecular weight heparin and aspirin, although only 75% of pregnancies are successful.

2.
Blood ; 134(Supplement_1): 4, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31724011

RESUMO

DISCLOSURES: Chaturvedi: Shire/Takeda: Research Funding; Sanofi: Consultancy; Alexion: Consultancy. Streiff:Pfizer: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Portola: Consultancy, Honoraria; Roche: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Honoraria. Petri:Astellas: Consultancy; Novartis: Consultancy; Exagen: Consultancy, Research Funding; Glenmark Pharmaceuticals: Consultancy; EMD Serono: Consultancy; Bristol-Myers Squibb: Consultancy; IQVIA: Consultancy; Janssen Pharmaceuticals: Consultancy; Aleon Pharmaceuticals: Consultancy; Momenta Pharmaceuticals: Consultancy; Blackrock Pharmaceuticals: Consultancy; Astrazeneca: Consultancy, Research Funding; UCB Pharmaceuticals: Consultancy; GSK: Consultancy; Qiagen: Consultancy; Abbive: Consultancy; Amgen: Consultancy; Decision Resources: Consultancy; Principia Biopharma: Consultancy; Eli Lilly: Consultancy; Kezaar Life Sciences: Consultancy. McCrae:Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Brodsky:Alexion: Membership on an entity's Board of Directors or advisory committees, Other: Grant funding; Achillion: Research Funding.

3.
Clin Rheumatol ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705325

RESUMO

INTRODUCTION: Smoking has been associated with increased incidence, severity of cutaneous lupus, and lupus activity. We looked at the association of both smoking and ethnicity with the individual damage items from the SLICC/ACR Damage Index. METHODS: Poisson regression was used to model the total SLICC/ACR Damage Index score against ever smoking. Cox regression was used to assess the relationship between time to individual damage items and ever smoking. Furthermore, we compared SLICC/ACR Damage Index items among African-American and Caucasian ever smokers. RESULTS: The study included 2629 patients, 52.6% Caucasian and 39.3% African-American. The prevalence of ever smokers was 35.8%. There was no significant difference in total SLICC/ACR Damage Index score between ever smokers and never smokers after adjustment for ethnicity, gender, age at diagnosis, and years of education. Ever smokers had more atherosclerotic cardiovascular damage and skin damage compared to non-smokers. Caucasian SLE patients who ever smoked were more likely to have muscle atrophy and atherosclerosis compared to Caucasian non-smokers. African-American patients who ever smoked were more likely to have skin damage compared to African-American non-smokers. African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked. CONCLUSION: Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Surprisingly, cardiovascular damage items had higher hazard ratios in Caucasian smokers than non-smokers while skin damage items hazard ratios were higher in African-American smokers compared to non-smokers.Key Points• This study is the largest cohort study to date evaluating the effect of smoking on the cumulative SLICC/ACR Damage Index and its individual damage items.• It is the only study that examined the effect of smoking on individual items of the SLICC/ACR Damage Index in terms of Caucasians vs. African-American ethnicity.• Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Compared to non-smokers, Caucasian smokers had higher risk of cardiovascular damage while African-American smokers had more skin damage.• African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31609532

RESUMO

OBJECTIVES: There is a paucity of data regarding healthcare costs associated with damage accrual in systemic lupus erythematosus (SLE). We describe costs associated with damage states across the disease course using multi-state modeling. METHODS: Patients from 33 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology (ACR) Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multi-state model. RESULTS: 1687 patients participated, 88.7% female, 49.0% of Caucasian race/ethnicity, mean age at diagnosis 34.6 years (SD 13.3), and mean follow up 8.9 years (range 0.6-18.5). Annual costs were higher in those with higher SDIs (SDI ≥ 5: $22 006 2019 CDN, 95% CI $16 662, $27 350 versus SDI=0: $1833, 95% CI $1134, $2532). Similarly, 10-year cumulative costs were higher in those with higher SDIs at the beginning of the 10-year interval (SDI ≥ 5: $189 073, 95% CI $142 318, $235 827 versus SDI=0: $21 713, 95% CI $13 639, $29 788). CONCLUSION: Patients with the highest SDIs incur 10-year cumulative costs that are almost 9-fold higher than those with the lowest SDIs. By estimating the damage trajectory and incorporating annual costs, damage can be used to estimate future costs, critical knowledge for evaluating the cost-effectiveness of novel therapies.

5.
Sci Rep ; 9(1): 15502, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664045

RESUMO

Systemic lupus erythematosus (SLE) is a heterogeneous disease with unpredictable patterns of activity. Patients with similar activity levels may have different prognosis and molecular abnormalities. In this study, we aimed to measure the main differences in drug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical data to build a machine learning classifier able to predict the SLE subset for individual patients. SLE transcriptomic data from two cohorts were compared with drug-induced gene signatures from the CLUE database to compute a connectivity score that reflects the capability of a drug to revert the patient signatures. Patient stratification based on drug connectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtained through longitudinal gene expression data, implying that differential treatment depends on the cluster to which patients belongs. The best drug candidates found, mTOR inhibitors or those reducing oxidative stress, showed stronger cluster specificity. We report that drug patterns for reverting disease gene expression follow the cell-specificity of the disease clusters. We used 2 cohorts to train and test a logistic regression model that we employed to classify patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to predict subset assignment and drug efficacy.

6.
J Autoimmun ; : 102340, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31629628

RESUMO

OBJECTIVE: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. METHODS: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). RESULTS: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03-1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). CONCLUSION: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.

7.
Arthritis Rheumatol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631561

RESUMO

These observed relationship between HCQ blood levels and risk of toxicity in these results is very similar to what we presented in the published paper. Second, we used logistic regression to determine whether there was still a statistically significant association between mean HCQ blood levels and retinopathy after adjusting for duration of time on HCQ. The results were similar to those seen in the paper and above (P-value=0.016, p-value for trend=0.003 after adjustment).

8.
Arthritis Rheumatol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631584

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC-FI values with damage accrual in the SLICC inception cohort. METHODS: The baseline visit was defined as the first at which both organ damage (SLICC/ACR Damage Index [SDI]) and health-related quality of life (Short-Form 36 [SF-36]) were assessed. Baseline SLICC-FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression estimated the association between baseline SLICC-FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. RESULTS: The 1549 SLE patients eligible for this analysis were mostly female (88.7%) with mean (standard deviation, SD) age 35.7 (13.3) years and median (interquartile range) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline SLICC-FI was 0.17 (0.08) with a range of 0-0.51. Over a mean (SD) follow-up of 7.2 (3.7) years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC-FI values (per 0.05 increment) were associated with higher rates of increase in the SDI during follow-up (Incidence Rate Ratio [IRR] 1.19; 95% CI 1.13-1.25), after adjusting for age, sex, ethnicity/region, education, baseline SLEDAI-2K, baseline SDI, and baseline use of corticosteroids, antimalarials, and immunosuppressives. CONCLUSION: The SLICC-FI predicts damage accrual in incident SLE, which further supports the SLICC-FI as a valid health measure in SLE.

9.
Sci Rep ; 9(1): 14433, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594956

RESUMO

Systemic lupus erythematosus (SLE) impacts multiple organ systems, although the causes of many individual SLE pathologies are poorly understood. This study was designed to elucidate organ-specific inflammation by identifying proteins that correlate with SLE organ involvement and to evaluate established biomarkers of disease activity across a diverse patient cohort. Plasma proteins and autoantibodies were measured across seven SLE manifestations. Comparative analyses between pathologies and correlation with the SLE Disease Activity Index (SLEDAI) were used to identify proteins associated with organ-specific and composite disease activity. Established biomarkers of composite disease activity, SLE-associated antibodies, type I interferon (IFN), and complement C3, correlated with composite SLEDAI, but did not significantly associate with many individual SLE pathologies. Two clusters of proteins were associated with renal disease in lupus nephritis samples. One cluster included markers of infiltrating leukocytes and the second cluster included markers of tissue remodelling. In patients with discoid lupus, a distinct signature consisting of elevated immunoglobulin A autoantibodies and interleukin-23 was observed. Our findings indicate that proteins from blood samples can be used to identify protein signatures that are distinct from established SLE biomarkers and SLEDAI and could be used to conveniently monitor multiple inflammatory pathways present in different organ systems.

10.
Arthritis Rheumatol ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532077

RESUMO

OBJECTIVE: In 2016, the American Academy of Ophthalmology (AAO) changed the recommended dosing of hydroxychloroquine from 6.5 mg/kg to less than 5 mg/kg. However, it is not clear that the lower prescribed dose of hydroxychloroquine will have the same efficacy for SLE activity or the same protective role against cardiovascular risk factors and thrombosis. We addressed the frequency of hydroxychloroquine retinopathy and the role of hydroxychloroquine blood levels to identify those at greater future risk of retinopathy. METHODS: 537 SLE patients in a large clinical cohort were repeatedly assessed for hydroxychloroquine blood levels and tested for hydroxychloroquine retinopathy. We assessed the risk of retinopathy by clinical characteristics and levels of hydroxychloroquine in the blood. RESULTS: The overall frequency of retinopathy was 4.3% (23/537). There was 1% risk of retinopathy in the first 5 years, 1.8% from 6 to 10 years, 3.3% from 11 to 15 years, 11.5% from 16 to 20 years, and 8.0% after 21 years of use. We found that older patients (p<0.0001), higher body mass index (p=0.0160 for trend) and longer duration of hydroxychloroquine intake (p=0.0024 and p=0.0006 for trend) were associated with higher risk of hydroxychloroquine toxicity. Higher hydroxychloroquine blood levels predicted later hydroxychloroquine retinopathy (p=0.0124 and p=0.0340 for mean and maximum HCQ blood levels respectively). CONCLUSION: Our data prove the utility of hydroxychloroquine blood levels in predicting retinopathy. This would allow clinicians to either decrease dose or increase monitoring in those with high blood levels.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31507071

RESUMO

BACKGROUND: Lupus Low Disease Activity State (LLDAS) is a potential treat to target goal in systemic lupus erythematosus (SLE). This study determined predictors of time to reach LLDAS in a longitudinal cohort. METHODS: Patients were grouped according to LLDAS status at cohort entry. Those who did not satisfy LLDAS at cohort entry were analyzed prospectively. The Kaplan Meier approach was used to estimate the time to LLDAS. Cox regression was used to identify patient characteristics that were associated with time to LLDAS. RESULTS: The probability of LLDAS attainment within one year was 52% for Caucasians, 36% for African-Americans and 33% for SLE patients with renal involvement. The median time to LLDAS was 1.1 years. In multivariable models, African-American ethnicity, baseline prednisone >10 mg daily, hypocomplementemia, baseline damage, and baseline renal activity remained significant predictors of longer time to attain LLDAS, while disease duration <1 year and cutaneous activity were associated with earlier attainment. CONCLUSIONS: LLDAS is potentially attainable in the majority of SLE patients. The time to LLDAS was found to be longer in African-American SLE patients. Characteristics of African-American SLE patients such as renal activity and hypocomplementemia were also independent predictors of slower attainment of LLDAS. These findings point to the need to include African-American SLE patients in both clinical and pharmaceutical research.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31502417

RESUMO

The Accelerating Medicines Partnership (AMP) Lupus Network was established as a partnership between the NIH, pharmaceutical companies, non-profit stakeholders and lupus investigators across multiple academic centers to apply high throughput technologies to the analysis of renal tissue, urine and blood from patients with lupus nephritis (LN). The AMP network provides publicly accessible data to the community with the goal of generating new scientific hypotheses and improving diagnostic and therapeutic tools so as to improve disease outcomes. We present here a description of the structure of the AMP Lupus Network and a summary of the preliminary results from the Phase 1 studies. The successful completion of Phase 1 sets the stage for analysis of a large cohort of LN samples in Phase 2 and provides a model for establishing similar discovery cohorts.

13.
JCI Insight ; 4(20)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31536480

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathologic T cell-B cell interactions and autoantibody production. Defining the T cell populations that drive B cell responses in SLE may enable design of therapies that specifically target pathologic cell subsets. Here, we evaluated the phenotypes of CD4+ T cells in the circulation of 52 SLE patients drawn from multiple cohorts and identified a highly expanded PD-1hiCXCR5-CD4+ T cell population. Cytometric, transcriptomic, and functional assays demonstrated that PD-1hiCXCR5-CD4+ T cells from SLE patients are T peripheral helper (Tph) cells, a CXCR5- T cell population that stimulates B cell responses via IL-21. The frequency of Tph cells, but not T follicular helper (Tfh) cells, correlated with both clinical disease activity and the frequency of CD11c+ B cells in SLE patients. PD-1hiCD4+ T cells were found within lupus nephritis kidneys and correlated with B cell numbers in the kidney. Both IL-21 neutralization and CRISPR-mediated deletion of MAF abrogated the ability of Tph cells to induce memory B cell differentiation into plasmablasts in vitro. These findings identify Tph cells as a highly expanded T cell population in SLE and suggest a key role for Tph cells in stimulating pathologic B cell responses.

14.
Arthritis Res Ther ; 21(1): 185, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391123

RESUMO

Following publication of the original article [1], it was brought to our attention that the fifth author's name was incorrectly published. The original article [1] is corrected.

15.
Arthritis Rheumatol ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390162

RESUMO

OBJECTIVES: In a multi-ethnic/racial, prospective SLE inception cohort, to determine the frequency, clinical characteristics, associations and outcomes in different types of peripheral nervous system (PNS) disease. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including seven types of PNS disease. SLE disease activity, organ damage, autoantibodies, patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,827 SLE patients, 88.8% were female, 48.8% Caucasian. The mean±SD age was 35.1±13.3 years, disease duration at enrollment 5.6±4.2 months and follow-up 7.6±4.6 years. There were 161 PNS events in 139/1,827 (7.6%) patients. The predominant events were peripheral neuropathy [66/161 (41.0%)], mononeuropathy [44/161 (27.3%)] and cranial neuropathy [39/161 (24.2%)] and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with prior history of neuropathy, older age at SLE diagnosis, higher SLEDAI-2K scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower SF-36 physical and mental component summary scores versus patients without NP events. By physician assessment, the majority of neuropathies resolved or improved over time and this was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. CONCLUSION: PNS disease is an important component of total NPSLE and has a significant negative impact on health related quality of life. The outcome is favourable for most patients, but we noted several factors associated with longer time to resolution. This article is protected by copyright. All rights reserved.

16.
J Thromb Haemost ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31364274

RESUMO

BACKGROUND: Variability remains a challenge in lupus anticoagulant (LA) testing. OBJECTIVE: To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry. METHODS: Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation. Non-anticoagulated registry samples were retested at the corresponding regional Core laboratories and anticoagulated samples at a single Core laboratory. Categorical agreement and discrepancies in LA status between Core and local/hospital laboratories were analyzed. RESULTS: Clotting times for the reference/characterized plasmas used for normalized ratios were similar between Core laboratories (CV <4%); precision and agreement for LA positive/negative plasma were similar (all CV ≤5%) in the four laboratories that completed both parts of the validation exercise; 418 registry samples underwent LA testing. Agreement for LA positive/negative status between Core and local/hospital laboratories was observed in 87% (115/132) non-anticoagulated and 77% (183/237) anticoagulated samples. However, 28.7% (120/418) of samples showed discordance between the Core and local/hospital laboratories or equivocal LA results. Some of the results of the local/hospital laboratories might have been unreliable in 24.7% (41/166) and 23% (58/252) of the total non-anticoagulated and anticoagulated samples, respectively. Equivocal results by the Core laboratory might have also contributed to discordance. CONCLUSIONS: Laboratories can achieve good agreement in LA performance by use of the same reagents, analyzer type, and protocols. The standardized Core laboratory results underpin accurate interpretation of APS ACTION clinical data.

17.
Medicina (Kaunas) ; 55(9)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438615

RESUMO

Background and Objectives: Atherosclerotic cardiovascular disease (CVD) remains a major cause of morbidity and mortality in persons with systemic lupus erythematosus (SLE, lupus). Atherosclerosis, which involves interplay between cholesterol metabolism and cellular inflammatory pathways, is primarily treated with statins since statins have lipid-lowering and anti-inflammatory properties. The Lupus Atherosclerosis Prevention Study (LAPS) was designed to investigate the efficacy of statins against CVD in SLE patients. LAPS demonstrated that 2 years of atorvastatin administration did not reduce atherosclerosis progression in lupus patients. In this LAPs substudy, we use cultured macrophages to explore the atherogenic properties of plasma from LAPS subjects to explain the mechanistic rationale for the inability of statins to reduce CVD in lupus. Materials and Methods: THP-1 differentiated macrophages were treated for 18 h with 10% SLE patient plasma obtained pre- and post-atorvastatin therapy or placebo. Gene expression of the following cholesterol transport genes was measured by qRT-PCR. For efflux-ATP binding cassette transporter (ABC)A1 and ABCG1, 27-hydroxylase, peroxisome proliferator-activated receptor (PPAR)γ, and liver X receptor (LXR)α; and for influx-cluster of differentiation 36 (CD36) and scavenger receptor (ScR)A1. Results: Macrophages exposed to plasma from both statin-treated and placebo-treated groups showed a significant decrease in cholesterol efflux proteins ATP binding cassette (ABC) transporters A1 and ABCG1, an increase in 27-hydroxylase, an increase in the LDL receptor and a decrease in intracellular free cholesterol. No change in influx receptors ScRA1 and CD36, nor nuclear proteins LXRα and PPARγ was observed. Conclusions: Statins do not normalize pro-atherogenic changes induced by lupus and these changes continue to worsen over time. This study provides mechanistic insight into LAPS findings by demonstrating that statins are overall ineffective in altering the balance of cholesterol transport gene expression in human macrophages. Furthermore, our study suggests that statins as a CVD treatment may not be useful in attenuating lipid overload in the SLE environment.

19.
Arthritis Res Ther ; 21(1): 176, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319876

RESUMO

OBJECTIVE: This study evaluates the utility of urinary pro-thrombotic molecules such as tissue factor (TF), anti-thrombotic molecules such as tissue factor pathway inhibitor (TFPI), and fibrinolytic molecules such as plasmin and d-dimer as biomarkers of lupus nephritis (LN). METHODS: Urine samples from 113 biopsy-proven LN patients (89 active LN and 24 inactive LN), 45 chronic kidney disease patients, and 41 healthy controls were examined for d-dimer, plasmin, TF, and TFPI levels by ELISA. The area under the receiver operating characteristic curve (AUC) analysis, multivariate regression analysis, and Bayesian network analysis were performed to assess the diagnostic value of the assayed molecules in LN. RESULTS: Although urinary d-dimer, plasmin, TF, and TFPI were all elevated in active LN compared to all control groups, and correlated with rSLEDAI and SLICC RAS disease activity indices, urine plasmin emerged as the strongest independent predictor of eGFR and renal disease status, by multivariate regression analysis and Bayesian network analysis. Whereas urine plasmin discriminated active LN from inactive disease with an AUC of 0.84, the combination of urine plasmin and TFPI discriminated ALN from ILN with an AUC of 0.86, with both surpassing the specificity and positive predictive value of traditional markers such as anti-dsDNA and complement C3. CONCLUSION: Both thrombogenic and thrombolytic cascades appear to be upregulated in lupus nephritis, with proteins from both cascades appearing in the urine. Of the coagulation cascade proteins surveyed, urine plasmin emerges as the strongest predictor of eGFR and clinical renal disease in patients with LN.

20.
J Rheumatol ; 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31203220

RESUMO

OBJECTIVE: Despite the high prevalence of cardiovascular disease among patients with systemic lupus erythematosus, the relationship between age, blood pressure, and blood pressure variability (BPV) is not well understood. We studied visit-to-visit BPV, its relationship to age, clinical, demographic characteristics and its potential role as a cardiovascular risk factor in patients with SLE. METHODS: We analyzed systolic and diastolic blood pressure measures in our cohort using mixed effects regression models. From these models, we then obtained estimates of the mean blood pressure, the visit-to-visit standard deviation and the between-person standard deviation. The estimated means were compared to general population using data from the National Health Statistics Reports from 2001-2008. In addition, we examined the relationship between blood pressures (means, variances), patient demographic, clinical characteristics, and subsequent cardiovascular events. RESULTS: The mean systolic blood pressure (SBP) in SLE increased with age and was significantly higher in younger patients compared to the general population. BPV in systemic lupus was elevated across all age. BPV was significantly higher in African Americans, in patients with traditional cardiovascular risk factors, those with high disease activity, and in patients taking prednisone. Hydroxychloroquine was associated with significantly lower BPV. Within-person variability in diastolic blood pressure of ≥9mmHg was highly associated with cardiovascular events in a multivariate analysis. CONCLUSION: Age-related blood pressure patterns in SLE differ from the general population. Increased visit-to-visit BPV is affected by many disease-specific and traditional cardiovascular factors. Increased diastolic BPV is highly associated with cardiovascular events in SLE.

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