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Start Over Author "Michael Belmont" Journal lupus science and medicine
22 results on '"Michael Belmont"'

1. 1012 Deep peripheral blood immunophenotyping identifies a subgroup of lupus nephritis patients characterized by high type 1 interferon signaling, persistent activated immune cells and poor renal response to standard of care at 1 year

Author

Richard Furie, Judith A James, Maria Dall’Era, Michelle A Petri, Chaim Putterman, Peter Izmirly, Jill P Buyon, Diane L Kamen, Betty Diamond, David Wofsy, Soumya Raychaudhuri, Jennifer Grossman, Fan Zhang, Jun Inamo, Nir Hacohen, Alice Horisberger, Kenneth C Kalunian, Michael B Brenner, Mariko Ishimori, David Hildeman, Robert Clancy, ANNE DAVIDSON, Matthias Kretzler, Michael Weisman, Celine C Berthier, Andrea Fava, Takanori Sasaki, Jennifer L Barnas, Jennifer H Anolik, Paul J Hoover, Deepak A Rao, Joshua Keegan, James A Lederer, Joel Guthridge, Michael Belmont, Arnon Arazi, William Apruzzese, Fernanda Payan-Schober, Jeffrey Hodgin, Thomas M Eisenhaure, Steve Woodle, Maureen A McMahon, Ekaterina Murzin, Katie Preisinger, Alec Griffith, Kaitlyn Howard, Tusharkanti Ghosh, Rebecca Beuschel, John Pulford, Brandon Hancock, and Maria Gutierrez-Arcelus

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2024
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2. LP-098 Proteomic analysis of histological lesions in lupus nephritis identifies an inflammatory signature of fibrous crescents

Author

Laurence S Magder, Michelle Petri, Jill Buyon, Peter Izmirly, Betty Diamond, Paride Fenaroli, Daniel W Goldman, ANNE DAVIDSON, Andrea Fava, Judith James, Michael Belmont, Jose Monroy-Trujillo, Mohamed G Atta, William Apruzzese, Jeffrey Hodgin, Derek Fine, Alessandra Ida Celia, Dwita Demeke, and Avi Rosenberg

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2023
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3. 619 Prospective Evaluation of anti-SSA/Ro Positive Pregnancies to Address Risk Factors for Fetal Cardiac Disease/Adverse Pregnancy Outcomes and Efficacy of Ambulatory Fetal Heart Rate Monitoring (FHRM) and Rapid Treatment of Emergent Block

Author

Amit Saxena, Jill Buyon, Peter Izmirly, Robert Clancy, Philip Carlucci, Paula Rackoff, Michael Belmont, Anita Moon-Grady, Mala Masson, Kristina Deonaraine, Nicola Fraser, Colin Phoon, Ashley Roman, Christina Penfield, Young Mi Lee, Julie Nusbaum, Bruce Solitar, Fardina Malik, Rebecca Haberman, Ruben Acherman, Elena Sinkovskaya, Alfred Albuhamad, Majd Makhoul, Gary Satou, Nelangi Pinto, Lisa Howley, Stephanie Levasseur, Jyothi Matta, Christopher Lindblade, Andrew Rubenstein, Caitlin Haxel, Katherine Kohari, Joshua Copel, James Strainic, Tam Doan, Karla Bermudez-Wagner, Shreya Sunil Sheth, Stacy Killen, Theresa Tacy, Michelle Kaplinski, Bailey Drewes, and Bettina Cuneo

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2022
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4. Pregnancy outcomes in antiphospholipid antibody positive patients: prospective results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (‘Registry’)

Author

Vittorio Pengo, Ricard Cervera, Angela Tincani, Michelle Petri, Jane Salmon, Guillermo Ruiz-Irastorza, Savino Sciascia, Massimo Radin, Paul R Fortin, Pierluigi Meroni, Cecilia Nalli, Maria G Tektonidou, Laura Andreoli, Yu Zuo, Denis Wahl, Medha Barbhaiya, Olga Amengual, Hannah Cohen, Zhuoli Zhang, Guillermo Pons-Estel, Ignasi Rodríguez-Pintó, Rosario Lopez-Pedrera, Maria Gerosa, Bahar Artim-Esen, Maria Laura Bertolaccini, Ann Clarke, Roger Levy, D Ware Branch, LanLan Ji, Giulia Pazzola, Doruk Erkan, Rohan Willis, Jason Knight, Ecem Sevim, Robert Roubey, Michael Belmont, Ian Mackie, Leslie Skeith, Zeynep Belce Erton, Guilherme Ramires de Jesús, Amaia Ugarte, Danieli Andrade, Maria Angeles Aguirre- Zamorano, Michael Lockshin, Emilio Gonzalez, Cecilia B Chighizola, Gustavo Balbi, Stephane Zuily, Maria Efthymiou, Esther Rodgriguez Almaraz, Silvia Foddai, Nina Kello, Jose Pardos-Gea, Flavio Signorelli, Stacy Davis, and Zhouli Zhang

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objectives To describe the outcomes of pregnancies in antiphospholipid antibody (aPL)-positive patients since the inception of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry.Methods We identified persistently aPL-positive patients recorded as ‘pregnant’ during prospective follow-up, and defined ‘aPL-related outcome’ as a composite of: (1) Preterm live delivery (PTLD) at or before 37th week due to pre-eclampsia (PEC), eclampsia, small-for-gestational age (SGA) and/or placental insufficiency (PI); or (2) Otherwise unexplained fetal death after the 10th week of gestation. The primary objective was to describe the characteristics of patients with and without aPL-related composite outcomes based on their first observed pregnancies following registry recruitment.Results Of the 55 first pregnancies observed after registry recruitment among nulliparous and multiparous participants, 15 (27%) resulted in early pregnancy loss

Published
2022
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5. Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) in the prediction of poor pregnancy outcomes in systemic lupus erythematosus (SLE)

Author

John Conklin, Thierry Dervieux, Peter Izmirly, H Michael Belmont, Jill P Buyon, Roberta Vezza Alexander, Michael Golpanian, and Alexis Engel

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Background Complement activation has been associated with adverse pregnancy outcomes (APO) in SLE. Pregnant women with SLE were studied to evaluate whether complement dysregulation within the first two pregnancy trimesters predicts APO.Methods Pregnant women fulfilled classification criteria for SLE. APO included neonatal death, preterm delivery before 36 weeks and small for gestational age newborn. Pre-eclampsia was also evaluated. Erythrocyte complement receptor 1 (ECR1) and erythrocyte-bound C4d (EC4d) were measured by flow cytometry. Complement proteins C3 and C4 were measured by immunoturbidimetry and anti-double-stranded DNA by ELISA in serum. Statistical analysis consisted of t-test, confusion matrix-derived diagnostic analysis, and multivariate logistic regression.Results Fifty-one women had 57 pregnancies and 169 visits during the study. Baseline visits occurred mainly in the first (n=32) and second trimester (n=21). Fourteen (24.6%) pregnancies resulted in 21 APO with preterm delivery being the most common (n=10). ECR1 0 indicated an elevated likelihood of pregnancy complications (DOR: 20.0 (95% CI: 3.64 to 109.97)).Conclusions Low levels of ECR1 in early or mid-pregnancy are predictive of an APO. Incorporating the weeks of gestation and both ECR1 and EC4d generated a PAI, which further predicted serious pregnancy complications.

Published
2022
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6. 1206 Evaluation of SARS-CoV-2 IgG antibody reactivity in a multi-racial/ethnic cohort of patients with systemic lupus erythematosus

Author

Rebecca H. Haberman, Ashira D Blazer, Peter M. Izmirly, Amit Saxena, Kristina K Deonaraine, Alexis J Engel, Mimi Y. Kim, Jose U. Scher, Mala Masson, Allison Guttmann, Ruth Fernandez-Ruiz, Jill P. Buyon, Rochelle Castillo, and H. Michael Belmont

Subjects
Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), RC581-607, Racial ethnic, Serology, Humoral immunity, Cohort, Immunology, Medicine, In patient, Immunologic diseases. Allergy, business, Antibody reactivity
Abstract

1206 Figure 1SARS-CoV-2 IgG in SLE[Figure omitted. See PDF]ConclusionsMost patients with SLE and confirmed COVID-19 were able to produce a serologic response despite use of a variety of immunosuppressants. These findings provide reassurances regarding the efficacy of humoral immunity and possible reinfection protection in patients with SLE.AcknowledgmentsData presented on behalf of the NYU WARCOV investigators. We thank Leora Horwitz for her assistance with the ICD-10 query at NYU. We also acknowledge Tania Moin and Ranit Shriky for assistance in navigating regulatory matters.

Published
2021

7. CS-31 Safety of hydroxychloroquine withdrawal in older adults with systemic lupus erythematosus

Author

Michael D. Lockshin, Jill P. Buyon, Chung-E Tseng, Jane E. Salmon, Peter M. Izmirly, H. Michael Belmont, Anca Askanase, Nicole Bornkamp, and Anna Zezon

Subjects
030203 arthritis & rheumatology, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Tofacitinib, Systemic lupus erythematosus, business.industry, Lupus nephritis, Hydroxychloroquine, Retrospective cohort study, medicine.disease, Rash, Discontinuation, 03 medical and health sciences, 0302 clinical medicine, Prednisone, Internal medicine, medicine, 030212 general & internal medicine, medicine.symptom, skin and connective tissue diseases, business, lcsh:RC581-607, medicine.drug
Abstract

Background Although hydroxychloroquine (HCQ) is a mainstay of treatment for patients with Systemic Lupus Erythematosus (SLE), ocular toxicity can result from accumulated exposure. The introduction of highly sensitive tools has engendered even more concern. As the longevity of patients with SLE improves, additional data will help physicians accurately balance the risk of ocular toxicity and the risk of disease flare, especially in older patients who have stable/quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients. Methods Data were obtained by retrospective chart review at three lupus centers. Twenty-seven patients met the following inclusion criteria:≥4 ACR criteria, disease duration ≥5 years, HCQ use of 200–400 mg per day ≥5 years, and discontinuation of hydroxychloroquine at ≥age 55 years. The comparator group comprised 39 age, gender and racial/ethnic matched patients who remained on HCQ. The primary outcome was a clinically meaningful flare within one year of HCQ withdrawal, defined as moderate or severe, using a revised version of the SELENA-SLEDAI Flare composite that separates mild from moderate flares, evaluates each organ system separately, and incorporates increases in corticosteroid dose and/or addition of immunosuppressive agents. Mild flares were considered secondary outcomes. Results Demographics are provided in table 1. There was a trend toward longer disease duration in the HCQ withdrawal group but no difference in prevalence of prior lupus nephritis between the groups. The reasons for HCQ withdrawal were maculopathy (n=13), presumed/biopsy proven cardiomyopathy (n=2), patient request (n=4), and miscellaneous other reasons (n=8). There was no difference in the primary or secondary outcomes between the groups (table 1). Two patients had a moderate flare after discontinuing HCQ, of whom one had arthritis treated with methotrexate and one had thrombocytopenia (>30K) and proteinuria of 2 grams/d (baseline 700 mg). Three patients had severe flares while continuing HCQ, of whom two were hospitalized, one for seizures and one for pericarditis; the third had worsening nephritis (urinary protein >4 g/d, requiring treatment). Two patients had moderate flares while remaining on HCQ, one of whom had a rash and arthritis treated with tofacitinib and one a rash treated with prednisone. Conclusions In this retrospective study of older patients with SLE on long-term HCQ, withdrawal did not increase the risk of moderate or severe flares. These data provide reassurance regarding the safety of withdrawing HCQ in stable older SLE patients.

Published
2018

8. 1002 Single cell transcriptomics in kidney tissue from African American patients enrolled in the accelerating medicines partnership (AMP) implicates tubular cells in the pathogenesis of APOL1 associated lupus nephritis

Author

Richard Furie, Brad Rovin, Michelle Petri, Judith A James, Kenneth Kalunian, Maria Dall’Era, Jill Buyon, Chaim Putterman, Peter Izmirly, Betty Diamond, David Wofsy, Ming Wu, Soumya Raychaudhuri, Philip M Carlucci, Qian Xiao, Nir Hacohen, Jennifer Anolik, H Michael Belmont, Robert Clancy, Kelly Ruggles, ANNE DAVIDSON, Deepak Rao, Celine C Berthier, Andrea Fava, Diane Kamen, Joel Guthridge, Arnon Arazi, Jose Monroy-Trujillo, Kristin Haag, William Apruzzese, Fernanda Payan-Schober, Kerry Cho, Joseph Mears, Wade DeJager, Paul Hoover, Kristina Deonaraine, Siddarth Gurajala, Derek Fine, Devyn Zaminski, Jasmine Shwetar, Katie Preisinger, and Sethu Madhavan

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2024
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10. 1009 In-depth analysis of myeloid cell subsets in lupus nephritis kidneys provides insights into disease mechanisms: lessons from the accelerating medicines partnership (AMP) in RA/SLE consortium

Author

Richard Furie, Joel M Guthridge, Judith A James, Maria Dall’Era, Michelle A Petri, Chaim Putterman, Jill P Buyon, Diane L Kamen, Betty Diamond, David Wofsy, Soumya Raychaudhuri, Thomas Tuschl, Jennifer Grossman, Peter M Izmirly, Qian Xiao, Nir Hacohen, Kenneth C Kalunian, Michael B Brenner, Mariko Ishimori, H Michael Belmont, Robert Clancy, ANNE DAVIDSON, Matthias Kretzler, Michael Weisman, Celine C Berthier, Andrea Fava, Jennifer L Barnas, Jennifer H Anolik, Paul J Hoover, Deepak A Rao, Arnon Arazi, William Apruzzese, Fernanda Payan-Schober, Joseph Mears, Saori Sakaue, James Lederer, Michael Peters, Tony Jones, Thomas M Eisenhaure, Siddarth Gurajala, Derek Fine, David A Hildeman, Steve Woodle, Maureen A McMahon, and Jeffery Hodgin

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2024
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12. Microvascular C5b-9 deposition in non-lesional skin in patients with SLE and its correlation with active lupus nephritis: a prospective observational study

Author

H Michael Belmont, Meghan Anderson, and Cynthia Magro

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objective Tissue damage in lupus nephritis (LN) is mediated by activation of the classical complement pathway. Complement-mediated upregulation of endothelial cell adhesion molecules is seen in dermal blood vessels of non-lesional skin of patients with active lupus. In diseases with systemic complement activation, extensive microvascular C5b-9 deposition is seen in non-lesional skin. In this study, we assess the presence of systemic complement pathway activation as determined by non-lesional skin microvascular C5b-9 deposition in patients with LN.Methods Eight patients with active LN and eight patients without active LN underwent non-lesional skin biopsies. Using a diaminobenzidine technique, specimens were evaluated for microvascular C5b-9 consistent with systemic complement pathway activation.Results Five of eight patients with active LN and one of eight patients without active LN demonstrated positive C5b-9 staining in non-lesional skin (p=0.04). Positive non-lesional C5b-9 staining has greater specificity, 87.5%, for active LN than pyuria, low complements, elevated double-stranded DNA (dsDNA) and proteinuria. Urine protein creatinine ratio was significantly higher in patients with positive non-lesional C5b-9 deposition (5.18 vs 1.20; p=0.04). C5b-9 deposition was not associated with a higher NIH Activity Index, interstitial fibrosis, dsDNA or lower complements.Conclusion This is the first study to demonstrate evidence in non-lesional skin of microvascular C5b-9 indicative of systemic complement pathway activation in LN. C5b-9 deposition is statistically more common and demonstrated greater specificity than most historical biomarkers for active LN. The findings support a potential role for microvascular C5b-9 assessment in non-lesional skin as a biomarker for LN activity.

Published
2023
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13. 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

Author

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

Subjects
Immunologic diseases. Allergy, RC581-607
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 Crithidia luciliae 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.

Published
2023
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14. LO-006 Change in urinary biomarkers at three months predicts 1-year treatment response of lupus nephritis better than proteinuria

Author

Richard Furie, Michelle Petri, Judith A James, Kenneth Kalunian, Maria Dall’Era, Jill Buyon, Chaim Putterman, Peter Izmirly, Betty Diamond, David Wofsy, Soumya Raychaudhuri, Daniel Goldman, Nir Hacohen, Jennifer Anolik, H Michael Belmont, Laurence Magder, Robert Clancy, ANNE DAVIDSON, Deepak Rao, Andrea Fava, Diane Kamen, Joel Guthridge, Celine Berthier, Arnon Arazi, Jose Monroy-Trujillo, Mohamed G Atta, William Apruzzese, Jennifer Barnas, Paul Hoover, Jeffrey Hodgin, Derek Fine, Alessandra Ida Celia, Avi Rosenberg, and Dawit Demeke

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2023
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15. 1107 Immune cell heterogeneity in lupus nephritis kidneys and its relation to histopathological features: lessons from the accelerating medicines partnership (AMP) in SLE Consortium

Author

Richard Furie, Joel M Guthridge, Judith A James, Maria Dall’Era, Michelle A Petri, Chaim Putterman, Jill P Buyon, Diane L Kamen, Betty Diamond, David Wofsy, Soumya Raychaudhuri, Thomas Tuschl, Jennifer Grossman, Peter M Izmirly, Qian Xiao, Nir Hacohen, Kenneth C Kalunian, Michael B Brenner, Mariko Ishimori, H Michael Belmont, Robert Clancy, ANNE DAVIDSON, Matthias Kretzler, Michael Weisman, Celine C Berthier, Andrea Fava, Jennifer L Barnas, Jennifer H Anolik, Paul J Hoover, Deepak A Rao, Arnon Arazi, William Apruzzese, Fernanda Payan-Schober, Saori Sakaue, James Lederer, Michael Peters, Tony Jones, Jospeh Mears, Thomas M Eisenhaure, Siddarth Gurajala, Derek Fine, David A Hildeman, Steve Woodle, Maureen A McMahon, and Jeffery Hodgin

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2022
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16. 1112 Change in urinary biomarkers at three months predicts 1-year treatment response of lupus nephritisbetter than proteinuria

Author

Judith A James, Maria Dall’Era, Jill Buyon, Peter Izmirly, Betty Diamond, Soumya Raychaudhuri, Nir Hacohen, Daniel W Goldman, H Michael Belmont, Laurence Magder, ANNE DAVIDSON, Deepak Rao, Andrea Fava, Arnon Arazi, Mohamed G Atta, William Apruzzese, Derek Fine, Joel Guthdridge, and Jose Monroy Trujillo

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2022
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17. 1702 Patients enrolled in the accelerating medicines partnership (AMP) RA/SLE network with isolated renal disease report minimal quality of life impairment on PROMIS-29 compared to patients with extrarenal symptoms

Author

Richard Furie, Michelle Petri, Judith A James, Kenneth Kalunian, Maria Dall’Era, Jill Buyon, Chaim Putterman, Peter Izmirly, Betty Diamond, Jessica Li, Jennifer Anolik, H Michael Belmont, Philip Carlucci, Deepak Rao, Andrea Fava, Diane Kamen, Celine Berthier, Jose Monroy-Trujillo, Kristin Haag, William Apruzzese, Sean Connery, Fernanda Payan-Schober, Kerry Cho, Kristina Deonaraine, Derek Fine, Heather T Gold, and Susana Serrate-Sztein

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2022
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20. Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Author

Andrew Filer, Michael H Weisman, Judith A James, Kenneth Kalunian, Michelle A Petri, Chaim Putterman, H Michael Belmont, Ilfita Sahbudin, Karim Raza, Maria Dall'Era, Jill P Buyon, Diane L Kamen, Karen Salomon-Escoto, Kazuyoshi Ishigaki, Patrick Dunn, David Wofsy, Michele Bombardieri, Vivian Bykerk, Myles Lewis, Ming Wu, Soumya Raychaudhuri, Hemant Suryawanshi, Thomas Tuschl, Christopher Ritchlin, Maureen McMahon, Jennifer Grossman, Philip M Carlucci, Alessandra Nerviani, Peter M Izmirly, Fan Zhang, Felice Rivellese, Joan Bathon, Zhu Zhu, Qian Xiao, Jessica Li, Holden Maecker, Nir Hacohen, Rong Mao, Jennifer Anolik, Javier Rangel-Moreno, Nida Meednu, Susan Goodman, Lindsy Forbess, Mariko Ishimori, Kevin Deane, David Hildeman, Yuhong Li, Laura Hughes, Robert Clancy, ANNE DAVIDSON, Matthias Kretzler, Larry Moreland, Harris Perlman, Peter Gregersen, Celine C Berthier, Andrea Fava, David Boyle, Derek M Fine, Ami Ben-Artzi, P J Utz, Melanie Smith, Beatrice Goilav, Carla Cuda, Andrew McDavid, Deepak A Rao, Joshua Keegan, Ilya Korsunsky, Joel Guthridge, Kevin Wei, Arnon Arazi, Thomas Eisenhaure, Michael Brenner, Susan Macwana, Pavel Morozov, Manjunath Kustagi, Gerald Watts, Kristina K Deonaraine, Jose Monroy-Trujillo, Mohamed G Atta, Kristin Haag, William Apruzzese, Sean Connery, Fernanda Payan-Schober, Kerry Cho, Jennifer Goff, Aparna Nathan, Joseph Mears, Nghia Millard, Kathryn Weinand, Saori Sakaue, Bill Robinson, Wade DeJager, Louis Bridges, Laura Donlin, Edward DiCarlo, Amit Lakhanpal, Heather Sherman, Anvita Singaraju, Lorien Shakib, Brendan Boyce, Darren Tabechian, Jen Albrecht, James Lederer, A Helena Jonsson, Daimon Simmons, Gregory Keras, Adam Chicoine, Zhihan Jian Li, Mandy McGeachy, Gary Firestein, Arnold Ceponis, Diane Horowitz, Salina Dominguez, Arthur Mandelin, Anjali Thakrar, Mike Holers, Jennifer Seifert, Constanino Pitzalis, Ellen Gravallese, Jennifer Barnas, Raymond Hsu, Steven Woodle, Paul Hoover, Michael Peters, Tony Jones, David Lieb, Jeffrey Hodgin, and Raji Menon

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

Published
2021
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21. Hydroxychloroquine is associated with lower platelet activity and improved vascular health in systemic lupus erythematosus

Author

H Michael Belmont, Jill P Buyon, MacIntosh Grant Cornwell, Elliot S Luttrell-Williams, Michael Golpanian, Hanane El Bannoudi, Khrystyna Myndzar, Stuart Katz, Nathaniel R Smilowitz, Alexis Engel, Robert Clancy, Kelly Ruggles, and Jeffrey S Berger

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objective Hydroxychloroquine (HCQ) is a mainstay of therapy in the treatment of SLE. The effect of HCQ on platelets and vascular health is uncertain. We investigated the relationship between HCQ use and dose with platelet activity, platelet transcriptomics and vascular health in patients with SLE.Methods Platelet aggregation, platelet mRNA expression and vascular health (sublingual capillary perfused boundary region (PBR), red blood cell filling (RBCF) and brachial artery reactivity testing) were analysed by HCQ use and dose.Results Among 132 subjects with SLE (age: 39.7±12.9 years, 97% female), 108 were on HCQ. SLE disease activity was similar between subjects on and off HCQ. Platelet aggregation in response to multiple agonists was significantly lower in patients on HCQ. There were inverse relationships between HCQ dose and gene expression pathways of platelet activity. Gene expression of P-selectin (SELP) was inversely correlated with HCQ dose (r=−0.41, p=0.003), which was validated at the protein level. Subjects on HCQ had improved vascular function correlating with HCQ dose as measured by lower PBR (r=−0.52, p=0.007), higher RBCF (r=0.55, p=0.004) and greater brachial artery reactivity (r=0.43, p=0.056).Conclusion HCQ use was associated with decreased platelet activation and activation-related transcripts and improved vascular health in SLE.

Published
2021
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