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Prevalence of cardiovascular events in a population-based registry of patients with systemic lupus erythematosus
Joyce, Daniel P; Berger, Jeffrey S; Guttmann, Allison; Hasan, Ghadeer; Buyon, Jill P; Belmont, H Michael; Salmon, Jane; Askanase, Anca; Bathon, Joan; Geraldino-Pardilla, Laura; Ali, Yousaf; Ginzler, Ellen M; Putterman, Chaim; Gordon, Caroline; Helmick, Charles G; Barbour, Kamil E; Gold, Heather T; Parton, Hilary; Izmirly, Peter M
BACKGROUND:The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls. METHODS:Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and the 2013-2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated. RESULTS:CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2-2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7-3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1-15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2-4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2-6.5) among patients aged 20-49 years and 2.2 (95%CI:2.1-2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5-12.1), Hispanic/Latino (10.9, 95%CI:10.5-11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20-49 had the highest CVE prevalence ratios. CONCLUSIONS:These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients.
PMCID:11401284
PMID: 39272198
ISSN: 1478-6362
CID: 5690842
Association of Autoantibody Concentrations and Trajectories With Lupus Nephritis Histologic Features and Treatment Response
Fava, Andrea; Wagner, Catriona A; Guthridge, Carla J; Kheir, Joseph; Macwana, Susan; DeJager, Wade; Gross, Tim; Izmirly, Peter; Belmont, H Michael; Diamond, Betty; Davidson, Anne; Utz, Paul J; Weisman, Michael H; Magder, Laurence S; ,; Guthridge, Joel M; Petri, Michelle; Buyon, Jill; James, Judith A
OBJECTIVE:Autoantibodies are a hallmark of lupus nephritis (LN), but their association with LN classes and treatment response are not adequately known. In this study, we quantified circulating autoantibodies in the Accelerating Medicines Partnership LN longitudinal cohort to identify serological biomarkers of LN histologic classification and treatment response and how these biomarkers change over time based on treatment response. METHODS:Peripheral blood samples were collected from 279 patients with systemic lupus erythematosus undergoing diagnostic kidney biopsy based on proteinuria. Of these, 268 were diagnosed with LN. Thirteen autoantibody specificities were measured by bead-based assays (Bio-Rad Bioplex 2200) and anti-C1q by enzyme-linked immunosorbent assay at the time of biopsy (baseline) and at 3, 6, and 12 months after biopsy. Clinical response was determined at 12 months. RESULTS:Proliferative LN (International Society of Nephrology/Renal Pathology Society class III/IV±V, n = 160) was associated with higher concentrations of anti-C1q, anti-chromatin, anti-double-stranded DNA (dsDNA), and anti-ribosomal P autoantibodies compared to nonproliferative LN (classes I/II/V/VI, n = 108). Anti-C1q and-dsDNA were independently associated with proliferative LN. In proliferative LN, higher baseline anti-C1q levels predicted complete response (area under the curve [AUC] 0.72; P = 0.002) better than baseline proteinuria (AUC 0.59; P = 0.21). Furthermore, all autoantibody levels except for anti-La/SSB decreased over 12 months in patients with proliferative, but not membranous, LN with a complete response. CONCLUSION/CONCLUSIONS:Baseline levels of anti-C1q and anti-dsDNA may serve as noninvasive biomarkers of proliferative LN, and anti-C1q may predict complete response at the time of kidney biopsy. In addition, tracking autoantibodies over time may provide further insights into treatment response and pathogenic mechanisms in patients with proliferative LN.
PMID: 38962936
ISSN: 2326-5205
CID: 5695772
Reply [Letter]
Buyon, Jill; Izmirly, Peter; Masson, Mala; Carlucci, Philip; Izmirly, Caroline G; Clancy, Robert; Cuneo, Bettina
PMID: 38233972
ISSN: 2326-5205
CID: 5662922
Extrarenal symptoms associate with worse quality of life in patients enrolled in the AMP RA/SLE Lupus Nephritis Network
Carlucci, Philip M; Preisinger, Katherine; Deonaraine, Kristina K; Zaminski, Devyn; Dall'Era, Maria; Gold, Heather T; Kalunian, Kenneth; Fava, Andrea; Belmont, H Michael; Wu, Ming; Putterman, Chaim; Anolik, Jennifer; Barnas, Jennifer L; Furie, Richard; Diamond, Betty; Davidson, Anne; Wofsy, David; Kamen, Diane; James, Judith A; Guthridge, Joel M; Apruzzese, William; Rao, Deepak; Weisman, Michael H; ,; Izmirly, Peter M; Buyon, Jill; Petri, Michelle
OBJECTIVE:Lupus nephritis (LN) can occur as an isolated component of disease activity or be accompanied by diverse extrarenal manifestations. Whether isolated renal disease is sufficient to decrease health related quality of life (HRQOL) remains unknown. This study compared Patient-Reported Outcomes Measurement Information System 29-Item (PROMIS-29) scores in LN patients with isolated renal disease to those with extrarenal symptoms to evaluate the burden of LN on HRQOL and inform future LN clinical trials incorporating HRQOL outcomes. METHODS:A total of 181 LN patients consecutively enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership completed PROMIS-29 questionnaires at the time of a clinically indicated renal biopsy. Raw PROMIS-29 scores were converted to standardized T scores. RESULTS:Seventy-five (41%) patients had extrarenal disease (mean age 34, 85% female) and 106 (59%) had isolated renal (mean age 36, 82% female). Rash (45%), arthritis (40%) and alopecia (40%) were the most common extrarenal manifestations. Compared with isolated renal, patients with extrarenal disease reported significantly worse pain interference, ability to participate in social roles, physical function, and fatigue. Patients with extrarenal disease had PROMIS-29 scores that significantly differed from the general population by > 0.5 SD of the reference mean in pain interference, physical function, and fatigue. Arthritis was most strongly associated with worse scores in these three domains. CONCLUSION/CONCLUSIONS:Most patients had isolated renal disease and extrarenal manifestations associated with worse HRQOL. These data highlight the importance of comprehensive disease management strategies that address both renal and extrarenal manifestations to improve overall patient outcomes.
PMID: 38530774
ISSN: 1462-0332
CID: 5644732
Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies
Buyon, Jill P; Masson, Mala; Izmirly, Caroline G; Phoon, Colin; Acherman, Ruben; Sinkovskaya, Elena; Abuhamad, Alfred; Makhoul, Majd; Satou, Gary; Hogan, Whitnee; Pinto, Nelangi; Moon-Grady, Anita; Howley, Lisa; Donofrio, Mary; Krishnan, Anita; Ahmadzia, Homa; Levasseur, Stephanie; Paul, Erin; Owens, Sonal; Cumbermack, Kristopher; Matta, Jyothi; Joffe, Gary; Lindblade, Christopher; Haxel, Caitlin; Kohari, Katherine; Copel, Joshua; Strainic, James; Doan, Tam; Bermudez-Wagner, Karla; Holloman, Conisha; Sheth, Shreya S; Killen, Stacy; Tacy, Theresa; Kaplinski, Michelle; Hornberger, Lisa; Carlucci, Philip M; Izmirly, Peter; Fraser, Nicola; Clancy, Robert M; Cuneo, Bettina F
OBJECTIVE:This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). METHODS:Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. RESULTS:Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. CONCLUSION/CONCLUSIONS:High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms.
PMID: 37947364
ISSN: 2326-5205
CID: 5655442
Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network
Izmirly, Peter M; Kim, Mimi Y; Carlucci, Philip M; Preisinger, Katherine; Cohen, Brooke Z; Deonaraine, Kristina; Zaminski, Devyn; Dall'Era, Maria; Kalunian, Kenneth; Fava, Andrea; Belmont, H Michael; Wu, Ming; Putterman, Chaim; Anolik, Jennifer; Barnas, Jennifer L; Diamond, Betty; Davidson, Anne; Wofsy, David; Kamen, Diane; James, Judith A; Guthridge, Joel M; Apruzzese, William; Rao, Deepak A; Weisman, Michael H; ,; Petri, Michelle; Buyon, Jill; Furie, Richard
BACKGROUND:Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. METHODS:Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. RESULTS: = 2.61 [95%CI = 0.93-7.33]; p = 0.069). CONCLUSIONS:CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.
PMCID:10877793
PMID: 38378664
ISSN: 1478-6362
CID: 5634232
Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis
Fava, Andrea; Buyon, Jill; Magder, Laurence; Hodgin, Jeff; Rosenberg, Avi; Demeke, Dawit S; Rao, Deepak A; Arazi, Arnon; Celia, Alessandra Ida; Putterman, Chaim; Anolik, Jennifer H; Barnas, Jennifer; Dall'Era, Maria; Wofsy, David; Furie, Richard; Kamen, Diane; Kalunian, Kenneth; James, Judith A; Guthridge, Joel; Atta, Mohamed G; Monroy Trujillo, Jose; Fine, Derek; Clancy, Robert; Belmont, H Michael; Izmirly, Peter; Apruzzese, William; Goldman, Daniel; Berthier, Celine C; Hoover, Paul; Hacohen, Nir; Raychaudhuri, Soumya; Davidson, Anne; Diamond, Betty; ,; Petri, Michelle
Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.
PMID: 38258904
ISSN: 2379-3708
CID: 5624822
Prevalence of concomitant rheumatologic diseases and autoantibody specificities among racial and ethnic groups in SLE patients
Denvir, Brendan; Carlucci, Philip M; Corbitt, Kelly; Buyon, Jill P; Belmont, H Michael; Gold, Heather T; Salmon, Jane E; Askanase, Anca; Bathon, Joan M; Geraldino-Pardilla, Laura; Ali, Yousaf; Ginzler, Ellen M; Putterman, Chaim; Gordon, Caroline; Barbour, Kamil E; Helmick, Charles G; Parton, Hilary; Izmirly, Peter M
OBJECTIVE/UNASSIGNED:Leveraging the Manhattan Lupus Surveillance Program (MLSP), a population-based registry of cases of systemic lupus erythematosus (SLE) and related diseases, we investigated the proportion of SLE with concomitant rheumatic diseases, including Sjögren's disease (SjD), antiphospholipid syndrome (APLS), and fibromyalgia (FM), as well as the prevalence of autoantibodies in SLE by sex and race/ethnicity. METHODS/UNASSIGNED:Prevalent SLE cases fulfilled one of three sets of classification criteria. Additional rheumatic diseases were defined using modified criteria based on data available in the MLSP: SjD (anti-SSA/Ro positive and evidence of keratoconjunctivitis sicca and/or xerostomia), APLS (antiphospholipid antibody positive and evidence of a blood clot), and FM (diagnosis in the chart). RESULTS/UNASSIGNED:1,342 patients fulfilled SLE classification criteria. Of these, SjD was identified in 147 (11.0%, 95% CI 9.2-12.7%) patients with women and non-Latino Asian patients being the most highly represented. APLS was diagnosed in 119 (8.9%, 95% CI 7.3-10.5%) patients with the highest frequency in Latino patients. FM was present in 120 (8.9%, 95% CI 7.3-10.5) patients with non-Latino White and Latino patients having the highest frequency. Anti-dsDNA antibodies were most prevalent in non-Latino Asian, Black, and Latino patients while anti-Sm antibodies showed the highest proportion in non-Latino Black and Asian patients. Anti-SSA/Ro and anti-SSB/La antibodies were most prevalent in non-Latino Asian patients and least prevalent in non-Latino White patients. Men were more likely to be anti-Sm positive. CONCLUSION/UNASSIGNED:Data from the MLSP revealed differences among patients classified as SLE in the prevalence of concomitant rheumatic diseases and autoantibody profiles by sex and race/ethnicity underscoring comorbidities associated with SLE.
PMCID:10956350
PMID: 38516120
ISSN: 2674-1199
CID: 5640792
Risk Assessment Model for Postpartum Venous Thromboembolism Prevention in Patients with Systemic Lupus Erythematosus
Griffin, Myah M; Engel, Alexis; Mehta-Lee, Shilpi S; Nusbaum, Julie; Golpanian, Michael; Izmirly, Peter; Belmont, H Michael; Buyon, Jill P
OBJECTIVE:This article assesses the application of the Royal College of Obstetricians and Gynaecologists (RCOG) venous thromboembolism (VTE) risk model on a cohort of postpartum patients with a history of systemic lupus erythematosus (SLE). STUDY DESIGN: < 0.05. RESULTS: = 3) were nevertheless recommended for VTE prophylaxis. No patients had a postpartum VTE regardless of therapy. CONCLUSION:These data reveal a need to improve upon providing postpartum VTE prophylaxis to SLE patients not in remission while also recognizing a diagnosis of SLE alone should not equate with active disease. Moreover, SLE patients in remission may still warrant VTE prophylaxis if other non-SLE-related risk factors are present. KEY POINTS:· Those with SLE are at increased risk for VTE postpartum.. · VTE prophylaxis should be instituted when clinically appropriate.. · Caution should be exercised in broadly assigning disease activity for SLE diagnosis only.. · This study supports VTE prophylaxis use in postpartum patients with SLE..
PMID: 37494484
ISSN: 1098-8785
CID: 5618842
Clinical implications of discordance between anti-dsDNA antibodies by multiplex flow immunoassay and Crithidia luciliae assay in a multiethnic racial cohort of patients with SLE
Zaminski, Devyn; Saxena, Amit; Izmirly, Peter; Buyon, Jill P; Belmont, H Michael
OBJECTIVE:immunofluorescence test (CLIFT). To address the clinical impact of measuring these antibodies by two different assays, this study leveraged a well-phenotyped multiethnic/racial cohort. METHODS:All patients fulfilled the classification criteria for SLE by at least one of the validated schemes: American College of Rheumatology, Systemic Lupus Erythematosus International Collaborating Clinics and/or American College of Rheumatology/European League Against Rheumatism classification criteria. Patients with one or more simultaneously paired anti-dsDNA by multiplex EIA and CLIFT were identified. Analysis of concordance or discordance, titre comparability of assays and association with hybrid SLE Disease Activity Index score, prevalence of lupus nephritis (LN), ability to predict a flare and classification criteria was performed. RESULTS:207 patients were simultaneously tested by EIA and CLIFT at least once for anti-dsDNA, generating 586 paired results. 377 pairs were concordant and 209 were discordant. 41 of 207 patients always had discordant paired results and 39 patients always had results with titre discordance. In 100 patients with LN, 60 were positive by EIA and 72 by CLIFT. Sensitivities and specificities for patients with LN versus patients without LN were EIA 60% and 47%, and CLIFT 72% and 37%, respectively. 42 patients had flare assessment within 90 days of their paired result. Six of seven patients with mild flares and all four patients with severe flares had concordant positive results. CONCLUSION:Our data demonstrate that discordance of positivity between both assays for anti-dsDNA is relatively common, occurring in a fifth of patients overall and a third of visits. EIA positivity is associated with LN less often than CLIFT positivity. With the significant discordance of results between anti-dsDNA assays, obtaining both CLIFT and EIA assays may be beneficial for classification and routine monitoring of SLE.
PMCID:10649789
PMID: 37963669
ISSN: 2053-8790
CID: 5610132