13 research outputs found
Ex vivo innate immune cytokine signature of enhanced risk of relapsing brucellosis.
BackgroundBrucellosis, a zoonotic infection caused by one of the Gram-negative intracellular bacteria of the Brucella genus, is an ongoing public health problem in Perú. While most patients who receive standard antibiotic treatment recover, 5-40% suffer a brucellosis relapse. In this study, we examined the ex vivo immune cytokine profiles of recovered patients with a history of acute and relapsing brucellosis.Methodology/principal findingsBlood was taken from healthy control donors, patients with a history of acute brucellosis, or patients with a history of relapsing brucellosis. Peripheral blood mononuclear cells were isolated and remained in culture without stimulation or were stimulated with a panel of toll-like receptor agonists or heat-killed Brucella melitensis (HKBM) isolates. Innate immune cytokine gene expression and protein secretion were measured by quantitative real-time polymerase chain reaction and a multiplex bead-based immunoassay, respectively. Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to controls. Notably, these include: basal and stimulus-induced expression of GM-CSF, TNF-α, and IFN-γ in response to LPS and HKBM; basal secretion of IL-6, IL-8, and TNF-α; and HKBM or Rev1-induced secretion of IL-1β, IL-2, GM-CSF, IFN-Υ, and TNF-α. Although acute and relapse patients were largely indistinguishable by their cytokine gene expression profiles, we identified a robust cytokine secretion signature that accurately discriminates acute from relapse patients. This signature consists of basal IL-6 secretion, IL-1β, IL-2, and TNF-α secretion in response to LPS and HKBM, and IFN-γ secretion in response to HKBM.Conclusions/significanceThis work demonstrates that informative cytokine variations in brucellosis patients can be detected using an ex vivo assay system and used to identify patients with differing infection histories. Targeted diagnosis of this signature may allow for better follow-up care of brucellosis patients through improved identification of patients at risk for relapse
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Ex vivo innate immune cytokine signature of enhanced risk of relapsing brucellosis.
BackgroundBrucellosis, a zoonotic infection caused by one of the Gram-negative intracellular bacteria of the Brucella genus, is an ongoing public health problem in Perú. While most patients who receive standard antibiotic treatment recover, 5-40% suffer a brucellosis relapse. In this study, we examined the ex vivo immune cytokine profiles of recovered patients with a history of acute and relapsing brucellosis.Methodology/principal findingsBlood was taken from healthy control donors, patients with a history of acute brucellosis, or patients with a history of relapsing brucellosis. Peripheral blood mononuclear cells were isolated and remained in culture without stimulation or were stimulated with a panel of toll-like receptor agonists or heat-killed Brucella melitensis (HKBM) isolates. Innate immune cytokine gene expression and protein secretion were measured by quantitative real-time polymerase chain reaction and a multiplex bead-based immunoassay, respectively. Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to controls. Notably, these include: basal and stimulus-induced expression of GM-CSF, TNF-α, and IFN-γ in response to LPS and HKBM; basal secretion of IL-6, IL-8, and TNF-α; and HKBM or Rev1-induced secretion of IL-1β, IL-2, GM-CSF, IFN-Υ, and TNF-α. Although acute and relapse patients were largely indistinguishable by their cytokine gene expression profiles, we identified a robust cytokine secretion signature that accurately discriminates acute from relapse patients. This signature consists of basal IL-6 secretion, IL-1β, IL-2, and TNF-α secretion in response to LPS and HKBM, and IFN-γ secretion in response to HKBM.Conclusions/significanceThis work demonstrates that informative cytokine variations in brucellosis patients can be detected using an ex vivo assay system and used to identify patients with differing infection histories. Targeted diagnosis of this signature may allow for better follow-up care of brucellosis patients through improved identification of patients at risk for relapse
Ex vivo innate immune cytokine signature of enhanced risk of relapsing brucellosis.
Brucellosis, a zoonotic infection caused by one of the Gram-negative intracellular bacteria of the Brucella genus, is an ongoing public health problem in Perú. While most patients who receive standard antibiotic treatment recover, 5-40% suffer a brucellosis relapse. In this study, we examined the ex vivo immune cytokine profiles of recovered patients with a history of acute and relapsing brucellosis.Blood was taken from healthy control donors, patients with a history of acute brucellosis, or patients with a history of relapsing brucellosis. Peripheral blood mononuclear cells were isolated and remained in culture without stimulation or were stimulated with a panel of toll-like receptor agonists or heat-killed Brucella melitensis (HKBM) isolates. Innate immune cytokine gene expression and protein secretion were measured by quantitative real-time polymerase chain reaction and a multiplex bead-based immunoassay, respectively. Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to controls. Notably, these include: basal and stimulus-induced expression of GM-CSF, TNF-α, and IFN-γ in response to LPS and HKBM; basal secretion of IL-6, IL-8, and TNF-α; and HKBM or Rev1-induced secretion of IL-1β, IL-2, GM-CSF, IFN-Υ, and TNF-α. Although acute and relapse patients were largely indistinguishable by their cytokine gene expression profiles, we identified a robust cytokine secretion signature that accurately discriminates acute from relapse patients. This signature consists of basal IL-6 secretion, IL-1β, IL-2, and TNF-α secretion in response to LPS and HKBM, and IFN-γ secretion in response to HKBM.This work demonstrates that informative cytokine variations in brucellosis patients can be detected using an ex vivo assay system and used to identify patients with differing infection histories. Targeted diagnosis of this signature may allow for better follow-up care of brucellosis patients through improved identification of patients at risk for relapse
PBMC cytokine gene expression after stimulation.
<p>Fold change of gene expression for IL-1β, GM-CSF, TNF-α, IFN-γ and IL-10 in PBMCs from control donors or acute or relapse brucellosis patients after stimulation with (A) LPS (B) Heat-killed <i>B. melitensis</i> or (C) R848 (asterisk indicates <i>p</i>≤0.05).</p
Basal PBMC cytokine secretion measured by multiplex immunoassay.
<p>IL-2, IL-6, IL-8, IL-10, and TNF-α secretion in unstimulated PBMCs from control donors or acute or relapse brucellosis patients (asterisk indicates <i>p</i>≤0.05). Concentrations indicated by open circles were extrapolated beyond the assay standard curve and values in the red shaded zone fell outside the observable range (OOR).</p
Hierarchical clustering of patients by gene expression or cytokine secretion.
<p>Control (green), acute (blue), and relapse (red) patients were clustered hierarchically by Euclidean distance in their scaled gene expression (A) or cytokine secretion (B) profiles (see <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002424#s2" target="_blank">Methods</a>). Response variables are grouped by cytokine, indicated in the left margin, and values are indicated by luminosity. Misclassification rates for each patient after 20 model selection runs are indicated underneath the corresponding patient code (see Supporting <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002424#pntd.0002424.s006" target="_blank">Table S1</a>).</p
Model selection and classification results.
<p>Response variables were selected and a linear discriminant classifier was trained using the transformed gene expression (A) or cytokine secretion data (B). The left panels show the results of 20 model selection runs, with the best-performing classifier highlighted in color. The variable included after each step in the forward selection is listed for the optimal model. Zero features is equivalent to random guessing. The center column shows all 33 patients after being mapped by the first (LD1) and second (LD2) linear discriminant functions used by the best-performing classifier. Classification performance is summarized by the confusion matrix on the right. This matrix gives the proportion of (C)ontrol, (A)cute, and (R)elapse patients that were correctly (on-diagonal) and incorrectly classified (off-diagonal).</p
Proceedings of the 2016 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Scientific Meeting
Table of Contents
P1 Serologic evidence of gut-driven systemic inflammation in juvenile idiopathic arthritis
Lampros Fotis, Nur Shaikh, Kevin Baszis, Anthony French, Phillip Tarr
P2 Oral health and anti-citrullinated peptide antibodies (ACPA) in juvenile idiopathic arthritis
Sriharsha Grevich, Peggy Lee, Sarah Ringold, Brian Leroux, Hannah Leahey, Megan Yuasa, Jessica Foster, Jeremy Sokolove, Lauren Lahey, William Robinson, Joshua Newsom, Anne Stevens
P3 Novel autoantigens for endothelial cell antibodies in pediatric rheumatic diseases identified by proteomics
Rie Karasawa, Mayumi Tamaki, Megumi Tanaka, Toshiko Sato, Kazuo Yudoh, James N. Jarvis
P4 Transcriptional profiling reveals monocyte signature associated with JIA patient poor response to methotrexate
Halima Moncrieffe, Mark F. Bennett, Monica Tsoras, Lorie Luyrink, Huan Xu, Sampath Prahalad, Paula Morris, Jason Dare, Peter A. Nigrovic, Margalit Rosenkranz, Mara Becker, Kathleen M. O’Neil, Thomas Griffin, Daniel J. Lovell, Alexei A. Grom, Mario Medvedovic, Susan D. Thompson
P5 A multi-dimensional genomic map for polyarticular juvenile idiopathic arthritis
Lisha Zhu, Kaiyu Jiang, Laiping Wong, Michael J Buck, Yanmin Chen, Halima Moncrieffe, Laura Brungs, Tao Liu, Ting Wang, James N Jarvis
P6 Tocilizumab for treatment of children with refractory JIA
Khaled Alsaeid, Jasim Alfailakawi, Hamid Alenezi, Hazim Alsaeed
P7 Clinical characteristics of the initial patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry
Tim Beukelman, Marc Natter, Norm Ilowite, Kelly Mieszkalski, Grendel Burrell, Brian Best, Helen Bristow, Shannon Carr, Anne Dennos, Rachel Kaufmann, Yukiko Kimura, Laura Schanberg
P8 Comparative performance of small and large clinical centers in a comprehensive pediatric rheumatology disease registry
Peter R Blier
P9 Clinical characteristics of children with membranous lupus nephritis: The Childhood Arthritis and Rheumatology Research Alliance Legacy Registry
Alexis Boneparth, Scott E. Wenderfer, L. Nandini Moorthy, Suhas M. Radhakrishna, Anna Carmela P. Sagcal-Gironella, Emily von Scheven
P10 Rituximab use in pediatric lupus anticoagulant hypoprothrombinemia syndrome - a two center experience
Kader Cetin Gedik, Salma Siddique, Cassyanne L. Aguiar, Doruk Erkan
P11 Predictors of complementary and alternative medicine use and response in children with musculoskeletal conditions
Ezra Cohen, Yvonne Lee, Michelle Dossett, Darshan Mehta, Roger Davis
P12 Comparison of pediatric rheumatology and nephrology survey results for the treatment of refractory proliferative lupus nephritis and renal flare in juvenile SLE
Mileka Gilbert, Beatrice Goilav, Esra Meidan, Joyce Hsu, Alexis Boneparth, Anabelle Chua, Stacy Ardoin, Scott E. Wenderfer, Emily Von Scheven, Natasha M. Ruth
P13 Transitioning lupus patients from pediatric to adult rheumatology
Joyce Hui-Yuen, Kader Cetin Gedik, Liza Bermudez, Ashlea Cook, Lisa Imundo, Amy Starr, Andrew Eichenfield, Anca Askanase
P14 The systemic juvenile idiopathic arthritis cohort of the Childhood Arthritis & Rheumatology Research Alliance Registry
Ginger Janow, Laura E. Schanberg, Soko Setoguchi, Victor Hasselblad, Elizabeth D. Mellins, Rayfel Schneider, Yukiko Kimura, The CARRA Legacy Registry Investigators
P15 Results of the pilot study of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans for new-onset systemic juvenile idiopathic arthritis
Yukiko Kimura, Sriharsha Grevich, Timothy Beukelman, Esi Morgan, T Brent Graham, Maria Ibarra, Yonit Sterba Ruas, Marisa Klein-Gitelman, Karen Onel, Sampath Prahalad, Marilynn Punaro, Sarah Ringold, Dana Toib, Heather Van Mater, Jennifer E. Weiss, Pamela F. Weiss, Kelly Mieszkalski, Laura E. Schanberg
P16 A systemic review of pain relief modalities in juvenile idiopathic arthritis: First step in developing a novel decision support intervention
Timothy S. H. Kwok, Jacinthe Bisaillon, Christine Smith, Lucie Brosseau, Jennifer Stinson, Adam M. Huber, Ciaran M. Duffy, Karine Toupin April
P17 Barriers and facilitators to care retention for pediatric systemic lupus erythematous patients in South Africa: A qualitative study
Laura B Lewandowski, Christiaan Scott
P18 Evaluating the feasibility of conducting comparative effectiveness studies in juvenile Localized Scleroderma (jLS)
Suzanne C. Li, Kathryn S. Torok, C. Egla Rabinovich, Sandy D. Hong, Mara L Becker, Fatma Dedeoglu, Maria F. Ibarra, Polly J Ferguson, Rob C. Fuhbrigge, Katie G. Stewart, Elena Pope, Ronald M. Laxer, Thomas G. Mason, Gloria C. Higgins, Xiaohu Li, Marilynn G. Punaro, George Tomlinson, Eleanor Pullenayegum, John Matelski, Laura Schanberg, Brian M. Feldman
P19 Tonsillar histology in patients with periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome
Kalpana Manthiram, Hernan Correa, Kathryn Edwards
P20 Clinical course of juvenile dermatomyositis presenting as skin predominant disease
Edward J. Oberle, Michelle Bayer, Dominic O. Co, Hatice Ezgi Baris, Yvonne Chiu, Adam Huber, Susan Kim
P21 A Survey of musculoskeletal ultrasound practices of pediatric rheumatologists in North America
Edward J Oberle, Timothy Beukelman
P22 Assessment, classification and treatment of calcinosis as a complication of juvenile dermatomyositis: A survey of pediatric rheumatologists by the Childhood Arthritis and Rheumatology Research Alliance
Amir B. Orandi, Kevin W. Baszis, Vikas Dharnidharka, Mark F. Hoeltzel, for the CARRA JDM Committee
P23 CARRA dermatomyositis CTP pilot study
Ann Reed, Adam Huber, George Tomlinson, Eleanor Pullenayegum, John Matelski, Y. Ingrid Goh, Laura Schanberg, Brian M. Feldman
P24 Unexpectedly high incidences and prolonged disease activity in children with chronic non-bacterial osteomyelitis (CNO) as compared to bacterial osteomyelitis
Anja Schnabel, Ursula Range, Gabriele Hahn, Timo Siepmann, Reinhard Berner, Christian Michael Hedrich
P25 Juvenile systemic sclerosis cohort within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry: Follow up characteristics
Brandi Stevens, Kathryn S. Torok, Suzanne Li, Nicole Hershey, Megan Curran, Gloria Higgins, Katharine Moore, Egla Rabinovich, Anne M. Stevens, for the CARRA Registry Investigators
P26 Development and usability testing of an iPad and desktop psycho-educational game for children with Juvenile Idiopathic Arthritis and their parents
Jennifer Stinson, Mark Connelly, Adam Huber, Nadia Luca, Lynn Spiegel, Argerie Tsimicalis, Stephanie Luca, Naweed Tajuddin, Roberta Berard, Julia Barsalou, Sarah Campillo, Paul Dancey, Ciaran Duffy, Brian Feldman, Nicole Johnson, Patrick McGrath, Natalie Shiff, Shirley Tse, Lori Tucker, Charles Victor
P27 iCanCope
TM: User-centred design and development of a smartphone app to support self-management for youth with arthritis pain
Jennifer Stinson, Chitra Lalloo, Lauren Harris, Joseph Cafazzo, Lynn Spiegel, Brian Feldman, Nadia Luca, Ronald Laxer
P28 Accessing pediatric rheumatology care: Despite barriers, few parents prefer telemedicine
Danielle R. Bullock, Richard K. Vehe, Lei Zhang, Colleen K. Correll1
P29 Exploration of factors contributing to time to achieve clinically inactive disease (CID) in juvenile idiopathic arthritis (JIA): A preliminary report
Suhas Ganguli, Max Shenberger, Ritesh Korumilli, Beth Gottlieb
P30 Pediatric rheumatology referral patterns: Presenting complaints of new patients at a large, urban academic center
Martha Rodriguez, Deirdre de Ranieri, Karen Onel, Linda Wagner-Weiner, Melissa Tesher
P31 Quality improvement (QI) initiatives in childhood systemic lupus erythematosus (cSLE)
Elizabeth Roth Wojcicki, Kristyn L. Maletta, Dominic O. Co, Marsha Malloy, Sarah Thomson, Judyann C. Olson
P32 Proliferative lupus nephritis in juvenile SLE: Support from the pediatric nephrology community for the definitions of responsiveness and flare in the 2012 consensus treatment plans
Scott E. Wenderfer, Mileka Gilbert, Joyce Hsu, Sangeeta Sule, Tamar B. Rubinstein, Beatrice Goilav, Daryl M. Okamura, Annabelle Chua, Laurence A. Greenbaum, Jerome C. Lane, Emily von Scheven, Stacy P. Ardoin, Natasha M. Ruth
P33 The steroid taper app: Making of a mobile app
Jennifer M. P. Woo, Marsha M. Malloy, James A. Jegers, Dustin J. Hahn, Mary K. Hintermeyer, Stacey M. Martinetti, Gretchen R. Heckel, Elizabeth L. Roth-Wojcicki, Dominic O. C