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  1. Article: Clinical implications of discordance between anti-dsDNA antibodies by multiplex flow immunoassay and

    Zaminski, Devyn / Saxena, Amit / Izmirly, Peter / Buyon, Jill P / Belmont, H Michael

    Lupus science & medicine

    2023  Volume 10, Issue 2

    Abstract: Objective: Anti-dsDNA antibodies (anti-dsDNA) are a component of all classification schemes in SLE and comprise one of the domains in validated activity indices. Anti-dsDNA is frequently measured commercially by an enzyme immunoassay (EIA) or : ... ...

    Abstract Objective: Anti-dsDNA antibodies (anti-dsDNA) are a component of all classification schemes in SLE and comprise one of the domains in validated activity indices. Anti-dsDNA is frequently measured commercially by an enzyme immunoassay (EIA) or
    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.
    MeSH term(s) Humans ; Fluorescent Antibody Technique ; Crithidia ; Lupus Erythematosus, Systemic/diagnosis ; Immunoassay/methods ; Lupus Nephritis/diagnosis ; DNA
    Chemical Substances anti-dsDNA autoantibody ; DNA (9007-49-2)
    Language English
    Publishing date 2023-11-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2779620-6
    ISSN 2053-8790
    ISSN 2053-8790
    DOI 10.1136/lupus-2023-001012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Proteomic Architecture of Valvular Extracellular Matrix: FNDC1 and MXRA5 Are New Biomarkers of Aortic Stenosis.

    Bouchareb, Rihab / Guauque-Olarte, Sandra / Snider, Justin / Zaminski, Devyn / Anyanwu, Anelechi / Stelzer, Paul / Lebeche, Djamel

    JACC. Basic to translational science

    2021  Volume 6, Issue 1, Page(s) 25–39

    Abstract: This study analyzed the expression of extracellular matrix (ECM) proteins during aortic valve calcification with mass spectrometry, and further validated in an independent human cohort using RNAseq data. The study reveals that valve calcification is ... ...

    Abstract This study analyzed the expression of extracellular matrix (ECM) proteins during aortic valve calcification with mass spectrometry, and further validated in an independent human cohort using RNAseq data. The study reveals that valve calcification is associated with significant disruption in ECM and metabolic pathways, and highlights a strong connection between metabolic markers and ECM remodeling. It also identifies FNDC1 and MXRA5 as novel ECM biomarkers in calcified valves, electing them as potential targets in the development and progression of aortic stenosis.
    Language English
    Publishing date 2021-01-13
    Publishing country United States
    Document type Journal Article
    ISSN 2452-302X
    ISSN (online) 2452-302X
    DOI 10.1016/j.jacbts.2020.11.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Platelets: Implications in Aortic Valve Stenosis and Bioprosthetic Valve Dysfunction From Pathophysiology to Clinical Care.

    Sellers, Stephanie L / Gulsin, Gaurav S / Zaminski, Devyn / Bing, Rong / Latib, Azeem / Sathananthan, Janarthanan / Pibarot, Philippe / Bouchareb, Rihab

    JACC. Basic to translational science

    2021  Volume 6, Issue 12, Page(s) 1007–1020

    Abstract: Aortic stenosis (AS) is the most common heart valve disease requiring surgery in developed countries, with a rising global burden associated with aging populations. The predominant cause of AS is believed to be driven by calcific degeneration of the ... ...

    Abstract Aortic stenosis (AS) is the most common heart valve disease requiring surgery in developed countries, with a rising global burden associated with aging populations. The predominant cause of AS is believed to be driven by calcific degeneration of the aortic valve and a growing body of evidence suggests that platelets play a major role in this disease pathophysiology. Furthermore, platelets are a player in bioprosthetic valve dysfunction caused by their role in leaflet thrombosis and thickening. This review presents the molecular function of platelets in the context of recent and rapidly evolving understanding the role of platelets in AS, both of the native aortic valve and bioprosthetic valves, where there remain concerns about the effects of subclinical leaflet thrombosis on long-term prosthesis durability. This review also presents the role of antiplatelet and anticoagulation therapies on modulating the impact of platelets on native and bioprosthetic aortic valves, highlighting the need for further studies to determine whether these therapies are protective and may increase the life span of surgical and transcatheter aortic valve implants. By linking molecular mechanisms through which platelets drive disease of native and bioprosthetic aortic valves with studies evaluating the clinical impact of antiplatelet and antithrombotic therapies, we aim to bridge the gaps between our basic science understanding of platelet biology and their role in patients with AS and ensuing preventive and therapeutic implications.
    Language English
    Publishing date 2021-11-17
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2452-302X
    ISSN (online) 2452-302X
    DOI 10.1016/j.jacbts.2021.07.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: 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

    Arthritis research & therapy

    2024  Volume 26, Issue 1, Page(s) 54

    Abstract: 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 ... ...

    Abstract 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: Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (OR
    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.
    MeSH term(s) Humans ; Lupus Nephritis/drug therapy ; Immunosuppressive Agents/therapeutic use ; Prospective Studies ; Creatinine ; Prednisone/therapeutic use ; Treatment Outcome ; Remission Induction ; Retrospective Studies ; Kidney
    Chemical Substances Immunosuppressive Agents ; Creatinine (AYI8EX34EU) ; Prednisone (VB0R961HZT)
    Language English
    Publishing date 2024-02-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2107602-9
    ISSN 1478-6362 ; 1478-6354
    ISSN (online) 1478-6362
    ISSN 1478-6354
    DOI 10.1186/s13075-024-03275-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: 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

    Rheumatology (Oxford, England)

    2024  

    Abstract: 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 ... ...

    Abstract 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: 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.
    Language English
    Publishing date 2024-03-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keae189
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Breakthrough SARS-CoV-2 infections, morbidity, and seroreactivity following initial COVID-19 vaccination series and additional dose in patients with SLE in New York City.

    Saxena, Amit / Engel, Alexis J / Banbury, Brittany / Hasan, Ghadeer / Fraser, Nicola / Zaminski, Devyn / Masson, Mala / Haberman, Rebecca H / Scher, Jose U / Ho, Gary / Law, Jammie / Rackoff, Paula / Tseng, Chung-E / Belmont, H Michael / Clancy, Robert M / Buyon, Jill P / Izmirly, Peter M

    The Lancet. Rheumatology

    2022  Volume 4, Issue 9, Page(s) e582–e585

    Language English
    Publishing date 2022-07-12
    Publishing country England
    Document type Journal Article
    ISSN 2665-9913
    ISSN (online) 2665-9913
    DOI 10.1016/S2665-9913(22)00190-4
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  7. Article ; Online: High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership.

    Carlucci, Philip M / Li, Jessica / Fava, Andrea / Deonaraine, Kristina K / Wofsy, David / James, Judith A / Putterman, Chaim / Diamond, Betty / Davidson, Anne / Fine, Derek M / Monroy-Trujillo, Jose / Atta, Mohamed G / DeJager, Wade / Guthridge, Joel M / Haag, Kristin / Rao, Deepak A / Brenner, Michael B / Lederer, James A / Apruzzese, William /
    Belmont, H Michael / Izmirly, Peter M / Zaminski, Devyn / Wu, Ming / Connery, Sean / Payan-Schober, Fernanda / Furie, Richard / Dall'Era, Maria / Cho, Kerry / Kamen, Diane / Kalunian, Kenneth / Anolik, Jennifer / Barnas, Jennifer / Ishimori, Mariko / Weisman, Michael H / Buyon, Jill P / Petri, Michelle

    Rheumatology (Oxford, England)

    2022  Volume 61, Issue 11, Page(s) 4335–4343

    Abstract: Objective: Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine ... ...

    Abstract Objective: Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1.
    Methods: A total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year.
    Results: At biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year.
    Conclusion: In this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1.
    MeSH term(s) Humans ; Lupus Nephritis ; Prospective Studies ; Incidence ; Proteinuria/diagnosis ; Kidney Function Tests ; Kidney/pathology
    Language English
    Publishing date 2022-02-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keac067
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