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Global comment on the use of hydroxychloroquine during the periconception period and pregnancy in women with autoimmune diseases

Schreiber, Karen; Giles, Ian; Costedoat-Chalumeau, Nathalie; Nelson-Piercy, Catherine; Dolhain, Radboud Jem; Mosca, Marta; Förger, Frauke; Fischer-Betz, Rebecca; Molto, Anna; Tincani, Angela; Pasquier, Elisabeth; Marin, Benoit; Elefant, Elisabeth; Salmon, Jane; Bermas, Bonnie L; Sammaritano, Lisa; Clowse, Megan E B; Chambers, Christina; Buyon, Jill; Inoue, Saori Abe; Agmon-Levin, Nancy; Aguilera, Silvia; Emadi, Samar Al; Andersen, Jeanette; Andrade, Danieli; Antovic, Aleksandra; Arnaud, Laurent; Christiansen, Alice Ashouri; Avcin, Tadej; Badreh-Wirström, Sara; Bertsias, George; Bini, Ilaria; Bobirca, Anca; Branch, Ware; Brucato, Antonio; Bultink, Irene; Capela, Susanna; Cecchi, Irene; Cervera, Ricard; Chighizola, Cecilia; Cobilinschi, Claudia; Cuadrado, Maria Jose; Dey, Dzifa; Etomi, Oseme; Espinosa, Gerard; Flint, Julia; Fonseca, João-Eurico; Fritsch-Stork, Ruth; Gerosa, Maria; Glintborg, Bente; Skorpen, Carina Gøtestam; Goulden, Bethan; Graversgaard, Christine; Gunnarsson, Iva; Gupta, Latika; Hetland, Merete; Hodson, Ken; Hunt, Beverley J; Isenberg, David; Jacobsen, Søren; Khamashta, Munther; Levy, Roger; Linde, Louise; Lykke, Jacob; Meissner, Yvette; Moore, Louise; Morand, Eric; Navarra, Sandra; Opris-Belinski, Daniela; Østensen, Monika; Ozawa, Hiroki; Perez-Garcia, Luis Fernando; Petri, Michelle; Pons-Estel, Guillermo J; Radin, Massimo; Raio, Luigi; Rottenstreich, Amihai; Ruiz-Irastorza, Guillermo; Tunjić, Slađana Rumpl; Rygg, Marite; Sciascia, Savino; Strangfeld, Anja; Svenungsson, Elisabet; Tektonidou, Maria; Troldborg, Anne; Vinet, Evelyne; Vojinovic, Jelena; Voss, Anne; Wallenius, Marianne; Andreoli, Laura
PMID: 38251494
ISSN: 2665-9913
CID: 5624622

Population-based prevalence and incidence estimates of mixed connective tissue disease from the Manhattan Lupus Surveillance Program

Hasan, Ghadeer; Ferucci, Elizabeth D; Buyon, Jill P; Belmont, H Michael; Salmon, Jane E; Askanase, Anca; Bathon, Joan M; Geraldino-Pardilla, Laura; Ali, Yousaf; Ginzler, Ellen M; Putterman, Chaim; Gordon, Caroline; Helmick, Charles G; Parton, Hilary; Izmirly, Peter M
OBJECTIVE:Epidemiologic data for mixed connective tissue disease (MCTD) are limited. Leveraging data from the Manhattan Lupus Surveillance Program (MLSP), a racially/ethnically diverse population-based registry of cases with SLE and related diseases including MCTD, we provide estimates of the prevalence and incidence of MCTD. METHODS:MLSP cases were identified from rheumatologists, hospitals, and population databases using a variety of ICD-9 codes. MCTD was defined as one of the following: 1) fulfillment of our modified Alarcon-Segovia and Kahn criteria which required a positive RNP antibody and the presence of synovitis, myositis, and Raynaud's phenomenon, 2) a diagnosis of MCTD and no other diagnosis of another connective tissue disease (CTD), and 3) a diagnosis of MCTD regardless of another CTD diagnosis. RESULTS:Overall, 258 (7.7%) of cases met a definition of MCTD. Using our modified Alarcon-Segovia and Kahn criteria for MCTD, the age-adjusted prevalence was 1.28 (95%CI 0.72-2.09) per 100 000. Using our definition of a diagnosis of MCTD and no other diagnosis of another CTD yielded an age-adjusted prevalence and incidence of MCTD of 2.98 (95%CI 2.10-4.11) per 100 000 and 0.39 (95%CI 0.22-0.64) per 100 000, respectively. The age-adjusted prevalence and incidence were highest using a diagnosis of MCTD regardless of other CTD diagnoses and were 16.22 (95%CI 14.00-18.43) per 100 000 and 1.90 (95%CI 1.49-2.39) per 100 000 respectively. CONCLUSIONS:The MLSP provided estimates for prevalence and incidence of MCTD in a diverse population. The variation in estimates using different case definitions is reflective of the challenge of defining MCTD in epidemiologic studies.
PMID: 36538873
ISSN: 1462-0332
CID: 5431852

Cutaneous neonatal lupus in patients with skin of color: A retrospective cohort study from a national registry

Kleitsch, Julianne; Mazori, Daniel R; Masson, Mala; Izmirly, Peter M; Saxena, Amit; Buyon, Jill P; Glick, Sharon A
PMID: 36997071
ISSN: 1097-6787
CID: 5463392

Machine learning identifies clusters of longitudinal autoantibody profiles predictive of systemic lupus erythematosus disease outcomes

Choi, May Yee; Chen, Irene; Clarke, Ann Elaine; Fritzler, Marvin J; Buhler, Katherine A; Urowitz, Murray; Hanly, John; St-Pierre, Yvan; Gordon, Caroline; Bae, Sang-Cheol; Romero-Diaz, Juanita; Sanchez-Guerrero, Jorge; Bernatsky, Sasha; Wallace, Daniel J; Isenberg, David Alan; Rahman, Anisur; Merrill, Joan T; Fortin, Paul R; Gladman, Dafna D; Bruce, Ian N; Petri, Michelle; Ginzler, Ellen M; Dooley, Mary Anne; Ramsey-Goldman, Rosalind; Manzi, Susan; Jönsen, Andreas; Alarcón, Graciela S; van Vollenhoven, Ronald F; Aranow, Cynthia; Mackay, Meggan; Ruiz-Irastorza, Guillermo; Lim, Sam; Inanc, Murat; Kalunian, Kenneth; Jacobsen, Søren; Peschken, Christine; Kamen, Diane L; Askanase, Anca; Buyon, Jill P; Sontag, David; Costenbader, Karen H
OBJECTIVES/OBJECTIVE:A novel longitudinal clustering technique was applied to comprehensive autoantibody data from a large, well-characterised, multinational inception systemic lupus erythematosus (SLE) cohort to determine profiles predictive of clinical outcomes. METHODS:Demographic, clinical and serological data from 805 patients with SLE obtained within 15 months of diagnosis and at 3-year and 5-year follow-up were included. For each visit, sera were assessed for 29 antinuclear antibodies (ANA) immunofluorescence patterns and 20 autoantibodies. K-means clustering on principal component analysis-transformed longitudinal autoantibody profiles identified discrete phenotypic clusters. One-way analysis of variance compared cluster enrolment demographics and clinical outcomes at 10-year follow-up. Cox proportional hazards model estimated the HR for survival adjusting for age of disease onset. RESULTS:Cluster 1 (n=137, high frequency of anti-Smith, anti-U1RNP, AC-5 (large nuclear speckled pattern) and high ANA titres) had the highest cumulative disease activity and immunosuppressants/biologics use at year 10. Cluster 2 (n=376, low anti-double stranded DNA (dsDNA) and ANA titres) had the lowest disease activity, frequency of lupus nephritis and immunosuppressants/biologics use. Cluster 3 (n=80, highest frequency of all five antiphospholipid antibodies) had the highest frequency of seizures and hypocomplementaemia. Cluster 4 (n=212) also had high disease activity and was characterised by multiple autoantibody reactivity including to antihistone, anti-dsDNA, antiribosomal P, anti-Sjögren syndrome antigen A or Ro60, anti-Sjögren syndrome antigen B or La, anti-Ro52/Tripartite Motif Protein 21, antiproliferating cell nuclear antigen and anticentromere B). Clusters 1 (adjusted HR 2.60 (95% CI 1.12 to 6.05), p=0.03) and 3 (adjusted HR 2.87 (95% CI 1.22 to 6.74), p=0.02) had lower survival compared with cluster 2. CONCLUSION/CONCLUSIONS:Four discrete SLE patient longitudinal autoantibody clusters were predictive of long-term disease activity, organ involvement, treatment requirements and mortality risk.
PMID: 37085289
ISSN: 1468-2060
CID: 5466422

The modifying influence of HLA class II DQB1∗06:02 on the Streptococcus and clinical phenotype correlation among anti-Ro+ mothers of children with neonatal lupus

Clancy, Robert M; Guthridge, Carla J; Marion, Miranda C; Guthridge, Joel; Howard, Timothy D; Izmirly, Peter M; Masson, Mala; Buyon, Jill P; James, Judith A; Langefeld, Carl D
PMCID:10311177
PMID: 37397545
ISSN: 2352-3042
CID: 5539022

Evaluation of the European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus in a Population Based Registry

Guttmann, Allison; Denvir, Brendan; Aringer, Martin; Buyon, Jill P; Belmont, H Michael; Sahl, Sara; Salmon, Jane E; Askanase, Anca; Bathon, Joan M; Geraldino-Pardilla, Laura; Ali, Yousaf; Ginzler, Ellen M; Putterman, Chaim; Gordon, Caroline; Helmick, Charles G; Parton, Hilary; Izmirly, Peter M
OBJECTIVE:Using the Manhattan Lupus Surveillance Program (MLSP), a multi-racial/ethnic population-based registry, we compared three commonly used classification criteria for Systemic Lupus Erythematosus (SLE) to identify unique cases and determine the incidence and prevalence of SLE using the EULAR/ACR criteria. METHODS:SLE cases were defined as fulfilling 1997 ACR, SLICC, or EULAR/ACR classification criteria. We quantified the number of cases uniquely associated with each and the number fulfilling all three. Prevalence and incidence using the EULAR/ACR classification criteria and associated 95% confidence intervals (CI) were calculated. RESULTS:1,497 cases fulfilled at least one of the three classification criteria, with 1,008 (67.3%) meeting all three classifications, 138 (9.2%) fulfilling only SLICC criteria, 35 (2.3%) fulfilling only ACR criteria and 34 (2.3%) uniquely fulfilling EULAR/ACR criteria. Patients solely satisfying EULAR/ACR criteria had fewer than four manifestations. The majority classified only by the ACR criteria did not meet any of the defined immunologic criteria. Patients fulfilling only SLICC criteria did so based on the presence of features unique to this system. Using the EULAR/ACR classification criteria, age-adjusted overall prevalence and incidence rates of SLE in Manhattan were 59.6 (95%CI:55.9-63.4) and 4.9 (95%CI 4.3-5.5) per 100,000 population, with age-adjusted prevalence and incidence rates highest among non-Hispanic Black females. CONCLUSION/CONCLUSIONS:Applying the three commonly used classification criteria to a population-based registry identified patients with SLE fulfilling only one validated definition. The most recently developed EULAR/ACR classification criteria revealed similar prevalence and incidence estimates to those previously established for the ACR and SLICC classification schemes.
PMID: 35638708
ISSN: 2151-4658
CID: 5235872

Platelet LGALS3BP Induces Myeloid Inflammation In Systemic Lupus Erythematosus

El Bannoudi, Hanane; Cornwell, MacIntosh; Luttrell-Williams, Elliot; Engel, Alexis; Rolling, Christina; Barrett, Tessa J; Izmirly, Peter; Belmont, H Michael; Ruggles, Kelly; Clancy, Robert; Buyon, Jill; Berger, Jeffrey S
OBJECTIVE:Platelets are mediators of inflammation with immune effector cell properties, and have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study investigated the role of platelet associated lectin galactoside-binding soluble 3 binding protein (LGALS3BP) as a mediator of inflammation in SLE, and a potential biomarker associated with clinical phenotypes. METHODS:We performed RNA sequencing on platelets of patients with SLE (n=54) and age, sex, and race-matched controls (n=18) and measured LGALS3BP in platelet releasate and in circulating serum. We investigated the association between levels of LGALS3BP with the prevalence, disease severity, and clinical phenotpyes of SLE, and studied platelet-mediated effects on myeloid inflammation. RESULTS:). Platelet-released LGALS3BP was highly correlated with circulating LGALS3BP (R = 0.69, p < 0.0001). Circulating LGALS3BP correlated with the SLE disease activity index (R = 0.32, p = 0.0006). Specifically, circulating LGALS3BP was higher in SLE patients with lupus nephritis than those with inactive disease (4.0 μg/mL vs 2.3 μg/mL, P < 0.001). IFN-α induced LGALS3BP transcription and translation in a megakaryoblastic cell line (MEG-01) cells in a dose-dependent manner. Recombinant LGALS3BP and platelet releasates from SLE patients enhanced pro-inflammatory cytokine production by macrophages. CONCLUSIONS:These data support that platelets act as potent effector cells contributing to the pathogenesis of SLE by secreting proinflammatory LGALS3BP, which also represents a novel biomarker of SLE clinical activity.
PMID: 36245285
ISSN: 2326-5205
CID: 5360062

Modeling of clinical phenotypes in systemic lupus erythematosus based on the platelet transcriptome and FCGR2a genotype

Cornwell, MacIntosh G; Bannoudi, Hanane El; Luttrell-Williams, Elliot; Engel, Alexis; Barrett, Tessa J; Myndzar, Khrystyna; Izmirly, Peter; Belmont, H Michael; Clancy, Robert; Ruggles, Kelly V; Buyon, Jill P; Berger, Jeffrey S
BACKGROUND:The clinical heterogeneity of SLE with its complex pathogenesis remains challenging as we strive to provide optimal management. The contribution of platelets to endovascular homeostasis, inflammation and immune regulation highlights their potential importance in SLE. Prior work from our group showed that the Fcγ receptor type IIa (FcγRIIa)-R/H131 biallelic polymorphism is associated with increased platelet activity and cardiovascular risk in SLE. The study was initiated to investigate the platelet transcriptome in patients with SLE and evaluate its association across FcγRIIa genotypes and distinct clinical features. METHODS:Fifty-one patients fulfilling established criteria for SLE (mean age = 41.1 ± 12.3, 100% female, 45% Hispanic, 24% black, 22% Asian, 51% white, mean SLEDAI = 4.4 ± 4.2 at baseline) were enrolled and compared with 18 demographically matched control samples. The FCGR2a receptor was genotyped for each sample, and RNA-seq was performed on isolated, leukocyte-depleted platelets. Transcriptomic data were used to create a modular landscape to explore the differences between SLE patients and controls and various clinical parameters in the context of FCGR2a genotypes. RESULTS:There were 2290 differentially expressed genes enriched for pathways involved in interferon signaling, immune activation, and coagulation when comparing SLE samples vs controls. When analyzing patients with proteinuria, modules associated with oxidative phosphorylation and platelet activity were unexpectedly decreased. Furthermore, genes that were increased in SLE and in patients with proteinuria were enriched for immune effector processes, while genes increased in SLE but decreased in proteinuria were enriched for coagulation and cell adhesion. A low-binding FCG2Ra allele (R131) was associated with decreases in FCR activation, which further correlated with increases in platelet and immune activation pathways. Finally, we were able to create a transcriptomic signature of clinically active disease that performed significantly well in discerning SLE patients with active clinical disease form those with inactive clinical disease. CONCLUSIONS:In aggregate, these data demonstrate the platelet transcriptome provides insight into lupus pathogenesis and disease activity, and shows potential use as means of assessing this complex disease using a liquid biopsy.
PMCID:10082503
PMID: 37029410
ISSN: 1479-5876
CID: 5459472

Autoimmune Congenital Complete Heart Block: How Late Can It Occur?

Makadia, Luv; Izmirly, Peter; Buyon, Jill P; Phoon, Colin K L
PMCID:10166639
PMID: 37168107
ISSN: 2157-6998
CID: 5544602

P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions

Rolling, Christina C; Sowa, Marcin A; Wang, Tricia T; Cornwell, MacIntosh; Myndzar, Khrystyna; Schwartz, Tamar; El Bannoudi, Hanane; Buyon, Jill; Barrett, Tessa J; Berger, Jeffrey S
BACKGROUND: Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain. OBJECTIVES/OBJECTIVE: To analyze the effect of platelets on monocyte activation and APT on MPA and platelet-induced monocyte activation. METHODS:, GP IIb/IIIa, and COX-1 inhibitors and assessed for platelet and monocyte activity via flow cytometry. RNA-Seq of monocytes incubated with platelets was used to identify platelet-induced monocyte transcripts and was validated by RT-qPCR in monocyte-PR co-incubation ± APT. RESULTS:inhibition attenuates platelet-induced monocyte activation.
PMID: 36630990
ISSN: 2567-689x
CID: 5418522