24 results on '"Christopher-Stine L"'
Search Results
2. FRI0284 Anti-Srp-Associated Autoimmune Myopathy: Younger Age at Onset Is Associated with More Severe Disease and Worse Outcome
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Pinal-Fernandez, I., primary, Parks, C., additional, Tiniakou, E., additional, Albayda, M., additional, Paik, J., additional, Lahouti, A., additional, Casal-Dominguez, M., additional, Pak, K., additional, Huang, W., additional, Lloyd, T.E., additional, Danoff, S., additional, Casciola-Rosen, L., additional, Christopher-Stine, L., additional, and Mammen, A.L., additional
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- 2016
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3. OP0010 Thigh Magnetic Resonance Imaging Reveals Increased Active and Chronic Muscle Damage in Necrotizing Myositis Compared To Polymyositis and Dermatomyositis
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Pinal-Fernandez, I., primary, Casal-Dominguez, M., additional, Lahouti, A., additional, Basharat, P., additional, Albayda, M., additional, Paik, J., additional, Ahlawat, S., additional, Danoff, S., additional, Lloyd, T.E., additional, Mammen, A.L., additional, Carrino, J., additional, and Christopher-Stine, L., additional
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- 2016
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4. FRI0273 Slow Recovery of Muscle Strength in Young Anti-HMG-COA Reductase Positive Myopathy Patients
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Tiniakou, E., primary, Pinal Fernandez, I., additional, Christopher-Stine, L., additional, Werner, J., additional, Lloyd, T., additional, Paik, J., additional, Albayda, J., additional, Danoff, S., additional, and Mammen, A., additional
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- 2016
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5. AB0623 Correlating Muscle Biopsy Features with Autoantibodies in Patients with Dermatomyositis and the Jo-1 Antisynthetase Syndrome
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Pinal-Fernandez, I., primary, Christopher-Stine, L., additional, Casciola-Rosen, L., additional, Corse, A., additional, and Mammen, A.L., additional
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- 2014
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6. FRI0483 Association between Muscle Enzymes, Acute-Phase Reactants and MRI Findings in Myositis
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Pinal-Fernandez, I., primary, Del Grande, M., additional, Filippo, D.G., additional, Carrino, J.A., additional, Mammen, A.L., additional, Lloyd, T.E., additional, and Christopher-Stine, L., additional
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- 2014
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7. SAT0471 Patient -reported outcomes in the idiopathic inflammatory myopathies
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Del Grande, M., primary, Bingham, C.O., additional, and Christopher-Stine, L., additional
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- 2013
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8. Lupus Atherosclerosis Prevention Study (LAPS)
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Petri, M. A., primary, Kiani, A. N., additional, Post, W., additional, Christopher-Stine, L., additional, and Magder, L. S., additional
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- 2010
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9. Lupus Atherosclerosis Prevention Study (LAPS).
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Petri, M A, Kiani, A N, Post, W, Christopher-Stine, L, and Magder, L S
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Background Cardiovascular disease is one of the major causes of death in systemic lupus erythematosus (SLE). A study was undertaken to investigate whether treatment with statins would reduce subclinical measures of atherosclerosis over a 2-year period. Methods 200 patients with SLE without clinical cardiovascular disease were randomised to receive atorvastatin 40 mg daily or an identical placebo. At baseline and after 2 years of follow-up, helical CT scanning (for coronary artery calcium) and carotid duplex (for intima media thickness/plaque) were performed. Patients were seen for measures of disease activity at 1 month, 3 months and quarterly thereafter. The primary outcome variable was change in coronary artery calcium. Results At baseline, 43% had coronary artery calcium. At 2 years there was no significant difference between the groups in progression of coronary artery calcium, carotid intima media thickness or carotid plaque. There was no significant difference between the groups in disease activity, measures of inflammation or endothelial cell activation. Conclusion This study provides no evidence that atorvastatin reduces subclinical measures of atherosclerosis or disease activity over 2 years in patients with SLE. In fact, it does not appear to reduce biochemical measures of inflammation. The anti-inflammatory effects of statins observed in the general population were not replicated in this SLE clinical trial. [ABSTRACT FROM PUBLISHER]
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- 2011
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10. Pathological autoantibody internalisation in myositis.
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Pinal-Fernandez I, Muñoz-Braceras S, Casal-Dominguez M, Pak K, Torres-Ruiz J, Musai J, Dell'Orso S, Naz F, Islam S, Gutierrez-Cruz G, Cano MD, Matas-Garcia A, Padrosa J, Tobias-Baraja E, Garrabou G, Aldecoa I, Espinosa G, Simeon-Aznar CP, Guillen-Del-Castillo A, Gil-Vila A, Trallero-Araguás E, Christopher-Stine L, Lloyd TE, Liewluck T, Naddaf E, Stenzel W, Greenberg SA, Grau JM, Selva-O'Callaghan A, Milisenda JC, and Mammen AL
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Objectives: Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption., Methods: Confocal immunofluorescence microscopy was employed to localise antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to examine the transcriptomic profiles of 669 samples, including those from patients with myositis, disease controls and healthy controls. Additionally, antibodies from myositis patients were introduced into cultured myoblasts through electroporation, and their transcriptomic profiles were analysed using RNA sequencing., Results: In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen. Bulk RNA sequencing revealed that muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibited transcriptomic patterns consistent with dysfunction of the autoantigen. For instance, in muscle biopsies from patients with anti-PM/Scl autoantibodies recognising components of the nuclear RNA exosome complex, an accumulation of divergent transcripts and long non-coding RNAs was observed; these RNA forms are typically degraded by the nuclear RNA exosome complex. Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. Further supporting evidence suggested that myositis autoantibodies recognising other autoantigens may also disrupt the function of their targets., Conclusions: This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)
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- 2024
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11. Current myositis clinical trials and tribulations.
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Saygin D, Werth V, Paik JJ, Park JK, Needham M, Lundberg IE, and Christopher-Stine L
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- Humans, Patient Reported Outcome Measures, Research Design, Clinical Trials as Topic, Myositis therapy, Myositis drug therapy
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With improved understanding of disease pathogenesis and availability of outcome measures, there has been a remarkable increase in the number of therapeutic clinical trials in idiopathic inflammatory myopathies (myositis) over the last three years reaching as many as five trials per site. These trials share similar design and inclusion/exclusion criteria resulting in a competitive clinical trial landscape in myositis. While these are exciting times for the myositis field, we have a number of concerns about the design and conduct of the myositis trials. These include competitive landscape, lengthy placebo arms, underrepresentation of minority groups among participants, use of patient reported outcome measures with limited/no data on validity in myositis, antiquated disease classification criteria, and unclear performance of the ACR/EULAR Myositis Response Criteria in skin-predominant patients despite inclusion of these patients in trials. In this viewpoint, we further discuss these concerns and offer potential solutions such as including patient perspectives in the trial design and adoption of innovative frameworks., Competing Interests: Competing interests: DS, JKP, MN, IEL, and LCS are members of the OMERACT Myositis Working Group. JJP received funding from NIAMS (K23AR073927); grants from Pfizer Inc, CORBUS, Kezar, Priovant and EMD Serono; royalty from Uptodate; and consulting fees from Pfizer, Kezar, Alexion, EMD Serono, Priovant and Guidepoint Inc. IEL received support from Swedish Research Council; consulting fees from Corbus Pharmaceutical, EMD Serono, ArgenX, Pfizer, Galapagos, Bristol Myers Squibb and Chugai; honoraria from Boehringer-Ingelheim; and currently holds stock in Roche and Novartis. MN received honorarium from Abcuro, Novartis, Sanofi-Aventis, Genzyme and Teva; participated on Data Safety Monitoring Board or Advisory Board for Abcuro, Teva and Sanofi-Genzyme; and received materials from Sanofi-Aventis. VW received grants from Pfizer, Corbus, CSL Behring, Priovant, Rome, Ventus and Horizon; received consulting fees from Pfizer, Janssen, Neovacs, Octapharma and CSL Behring; and University of Pennsylvania owns the copyright for the Cutaneous Dermatomyositis Disease Area and Severity Index. LCS received grants from Pfizer, Corbus, Kezar; royalties for IP related to anti-HMGCR assay from Inova Diagnostics; consulting fees from Janssen, Boehringer-Ingelheim, Mallincrodt, EMD Serono, ArgenX, Allogene, Pfizer, Horizon Therapeutics, Octopharma and NuVig; received payment for expert testimony from Bendin Sumrall and Ladner LLC, Feldman, Kleidman Coffey & Sappe LLP, Downs Ward Bender Hauptmann & Herzog, PA, Sulloway and Hollis, received support for attending meetings and travel from Octapharma and has patent with Inova Diagnostics/RDL., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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12. Response to: Correspondence on 'Current myositis clinical trials and tribulations' by Saygin et al .
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Saygin D, Werth V, Paik JJ, Park JK, Needham M, Lundberg IE, and Christopher-Stine L
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Competing Interests: Competing interests: None declared.
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- 2024
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13. Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies.
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Pinal-Fernandez I, Milisenda JC, Pak K, Muñoz-Braceras S, Casal-Dominguez M, Torres-Ruiz J, Dell'Orso S, Naz F, Gutierrez-Cruz G, Duque-Jaimez Y, Matas-Garcia A, Padrosa J, Garcia-Garcia FJ, Guitart-Mampel M, Garrabou G, Trallero-Araguás E, Walitt B, Paik JJ, Albayda J, Christopher-Stine L, Lloyd TE, Grau-Junyent JM, Selva-O'Callaghan A, and Mammen AL
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- Humans, Autoantibodies, Mi-2 Nucleosome Remodeling and Deacetylase Complex genetics, Muscle, Skeletal pathology, Dermatomyositis genetics, Myositis, Myositis, Inclusion Body, Autoimmune Diseases
- Abstract
Objectives: Myositis is a heterogeneous family of diseases including dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), antisynthetase syndrome (AS) and inclusion body myositis (IBM). Myositis-specific autoantibodies define different subtypes of myositis. For example, patients with anti-Mi2 autoantibodies targeting the chromodomain helicase DNA-binding protein 4 (CHD4)/NuRD complex (a transcriptional repressor) have more severe muscle disease than other DM patients. This study aimed to define the transcriptional profile of muscle biopsies from anti-Mi2-positive DM patients., Methods: RNA sequencing was performed on muscle biopsies (n=171) from patients with anti-Mi2-positive DM (n=18), DM without anti-Mi2 autoantibodies (n=32), AS (n=18), IMNM (n=54) and IBM (n=16) as well as 33 normal muscle biopsies. Genes specifically upregulated in anti-Mi2-positive DM were identified. Muscle biopsies were stained for human immunoglobulin and protein products corresponding to genes specifically upregulated in anti-Mi2-positive muscle biopsies., Results: A set of 135 genes, including SCRT1 and MADCAM1 , was specifically overexpressed in anti-Mi2-positive DM muscle. This set was enriched for CHD4/NuRD-regulated genes and included genes that are not otherwise expressed in skeletal muscle. The expression levels of these genes correlated with anti-Mi2 autoantibody titres, markers of disease activity and with the other members of the gene set. In anti-Mi2-positive muscle biopsies, immunoglobulin was localised to the myonuclei, MAdCAM-1 protein was present in the cytoplasm of perifascicular fibres, and SCRT1 protein was localised to myofibre nuclei., Conclusions: Based on these findings, we hypothesise that anti-Mi2 autoantibodies could exert a pathogenic effect by entering damaged myofibres, inhibiting the CHD4/NuRD complex, and subsequently derepressing the unique set of genes defined in this study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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14. Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis.
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Pinal-Fernandez I, Quintana A, Milisenda JC, Casal-Dominguez M, Muñoz-Braceras S, Derfoul A, Torres-Ruiz J, Pak K, Dell'Orso S, Naz F, Gutierrez-Cruz G, Milone M, Shelly S, Duque-Jaimez Y, Tobias-Baraja E, Matas-Garcia A, Garrabou G, Padrosa J, Ros J, Trallero-Araguás E, Walitt B, Christopher-Stine L, Lloyd TE, Zhao C, Swift S, Rajan A, Grau-Junyent JM, Selva-O'Callaghan A, Liewluck T, and Mammen AL
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- Humans, Immune Checkpoint Inhibitors, Transcriptome, Interleukin-6 metabolism, Interferons genetics, Muscle, Skeletal pathology, Dermatomyositis genetics, Myocarditis pathology, Myositis chemically induced, Myositis genetics, Autoimmune Diseases complications, Myositis, Inclusion Body
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Objectives: Inflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICIs) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis., Methods: Bulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM and two IBM)., Results: Unsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1 and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed coexisting myocarditis. ICI-MYO2 was composed of patients with predominant necrotising pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway., Conclusions: We identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICI-DM and ICI-MYO1 and only ICI-MYO1 patients developed myocarditis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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15. Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies.
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Hosono Y, Sie B, Pinal-Fernandez I, Pak K, Mecoli CA, Casal-Dominguez M, Warner BM, Kaplan MJ, Albayda J, Danoff S, Lloyd TE, Paik JJ, Tiniakou E, Aggarwal R, Oddis CV, Moghadam-Kia S, Carmona-Rivera C, Milisenda JC, Grau-Junyent JM, Selva-O'Callaghan A, Christopher-Stine L, Larman HB, and Mammen AL
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- Humans, Autoantibodies, Sp4 Transcription Factor, Dermatomyositis, Myositis, Neoplasms, Arthritis, Rheumatoid
- Abstract
Objectives: In dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies., Methods: Phage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren's syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies., Results: Anti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer., Conclusions: Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk., Competing Interests: Competing interests: YJ, IP-F, KP, MC-D, MJK, JA, TEL, ET, CVO, SM-K, CC-R, JCM, JMG-J, AS-O'C and ALM report no competing interests. CAM has received support from NIH grant 1K23AR075898 and the Jerome L. Greene Foundation; reconsulting fees from Guidepoint Consultations and Boehringer Ingelheim; and payment for expert testimony from the Department of Justice–Vaccine Injury Compensation Program. BMW received support from NIH grant Z01-DE000704. SD received support grants or contract from BMS, Boehringer-Ingelheim and Genentech/Roche; royalties or licences from UpToDate; consulting fees from Boehringer-Ingelheim; payment for presentations from France Foundation; support for travel from Boehringer-Ingelheim; participates in an advisory board for Galecto and Galapagos; and is a senior medical advisor for the Pulmonary Fibrosis Foundation and the American Thoracic Society. JJP received support from NIH grant K23AR073927; grants or contracts from Pfizer, Kezer and Corbus; royalties from UpToDate; and consulting fees from Pfizer, Kezar, EMD Serono, Proivant and Guidepoint Consultation. RA received grants or contracts from Mallinckrodt, Q32, Pfizer, EMD-Serono and Bristol Myers-Squibb; and consulting fees from Mallinckrodt, EMD Serono, Octapharma, Kezar, CSL Behring, Pfizer, Bristol Myers-Squibb, Astrazeneca, Alexion, Boehringer-Ingelheim, Argenx, Corbus, Roivant, Jannsen, Merck, Kyverna, Galapagos, Actigraph, Abbvie, Scipher, Horizon Therapeutics, Teva and Beigene. LC-S received grants or contracts from Pfizer, Corbus and Kezar; royalties from Inova Diagnostics; consulting fees from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Argenx, Allogene and Horizon Therapeutics; expert testimony for Bendin Sumrall and Ladner LLC, Feldman, Kleidman Coffey, & Sappe LLP Downs Ward Bender Hauptmann & Herzog, P.A., and Sulloway and Hollis; and patents from Inova Diagnostics and RDL. HBL received support from NIH grant R01GM136724; is a founder of ImmuneID, Portal Bioscience and Alchemab; and is an advisor to TScan Therapeutics., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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16. Attenuated response to fourth dose SARS-CoV-2 vaccination in patients with autoimmune disease: a case series.
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Teles M, Connolly CM, Frey S, Chiang TP, Alejo JL, Boyarsky BJ, Shah AA, Albayda J, Christopher-Stine L, Werbel WA, Segev DL, and Paik JJ
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- COVID-19 Vaccines, Humans, SARS-CoV-2, Vaccination adverse effects, Autoimmune Diseases drug therapy, Autoimmune Diseases etiology, COVID-19 prevention & control
- Abstract
Competing Interests: Competing interests: DLS has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, Thermo Fisher Scientific. LC-S has the following financial disclosures: consultant fees from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Allogene and ArgenX. The other authors of this manuscript have no financial disclosures or completing interest to disclose as described by Annals of the Rheumatic Diseases.
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- 2022
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17. Temporary hold of mycophenolate augments humoral response to SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases: a case series.
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Connolly CM, Chiang TP, Boyarsky BJ, Ruddy JA, Teles M, Alejo JL, Massie A, Werbel WA, Shah AA, Christopher-Stine L, Garonzik-Wang J, Segev DL, and Paik JJ
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- Adult, Aged, Antibodies, Viral blood, Antibodies, Viral immunology, COVID-19 immunology, Female, Humans, Male, Middle Aged, Musculoskeletal Diseases drug therapy, Musculoskeletal Diseases virology, Mycophenolic Acid immunology, Prospective Studies, Rheumatic Diseases drug therapy, Rheumatic Diseases virology, SARS-CoV-2 immunology, Young Adult, COVID-19 prevention & control, COVID-19 Vaccines immunology, Immunity, Humoral drug effects, Musculoskeletal Diseases immunology, Mycophenolic Acid administration & dosage, Rheumatic Diseases immunology, Withholding Treatment
- Abstract
Competing Interests: Competing interests: DLS, MD PhD, has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, Thermo Fisher Scientific.Lisa Christopher-Stine has the following financial disclosures: consultant fees from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Allogene and ArgenX.
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- 2022
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18. Booster-dose SARS-CoV-2 vaccination in patients with autoimmune disease: a case series.
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Connolly CM, Teles M, Frey S, Boyarsky BJ, Alejo JL, Werbel WA, Albayda J, Christopher-Stine L, Garonzik-Wang J, Segev DL, and Paik JJ
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- Adult, Aged, Antibodies, Viral blood, Antibodies, Viral immunology, Autoimmune Diseases virology, COVID-19 immunology, Female, Humans, Male, Middle Aged, Prospective Studies, Autoimmune Diseases immunology, COVID-19 prevention & control, COVID-19 Vaccines immunology, Immunity, Humoral immunology, SARS-CoV-2 immunology
- Abstract
Competing Interests: Competing interests: DLS has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, Thermo Fisher Scientific. LC-S has the following financial disclosures: consultant fees from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Allogene and ArgenX.
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- 2022
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19. Antibody response to the Janssen/Johnson & Johnson SARS-CoV-2 vaccine in patients with rheumatic and musculoskeletal diseases.
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Chiang TP, Connolly CM, Ruddy JA, Boyarsky BJ, Alejo JL, Werbel WA, Massie A, Christopher-Stine L, Garonzik-Wang J, Segev DL, and Paik JJ
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- Antibody Formation, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19, Musculoskeletal Diseases
- Abstract
Competing Interests: Competing interests: DLS has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt and Thermo Fisher Scientific. LC-S has the following financial disclosures: consultant fees from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Allogene and ArgenX. The other authors of this manuscript have no financial disclosures or conflicts of interest to disclose as described by the Annals of the Rheumatic Diseases.
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- 2021
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20. High antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with rheumatic and musculoskeletal diseases.
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Ruddy JA, Connolly CM, Boyarsky BJ, Werbel WA, Christopher-Stine L, Garonzik-Wang J, Segev DL, and Paik JJ
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- Adult, Aged, Antibodies, Viral blood, Antibodies, Viral immunology, Antirheumatic Agents therapeutic use, Female, Humans, Immunogenicity, Vaccine drug effects, Male, Middle Aged, Rheumatic Diseases drug therapy, SARS-CoV-2, COVID-19 prevention & control, Immunocompromised Host immunology, Immunogenicity, Vaccine immunology, Rheumatic Diseases immunology
- Abstract
Competing Interests: Competing interests: DLS has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt and Thermo Fisher Scientific. LC-S has the following financial disclosures: consultant fees from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Allogene and ArgenX.
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- 2021
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21. Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis.
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Pinal-Fernandez I, Casal-Dominguez M, Derfoul A, Pak K, Miller FW, Milisenda JC, Grau-Junyent JM, Selva-O'Callaghan A, Carrion-Ribas C, Paik JJ, Albayda J, Christopher-Stine L, Lloyd TE, Corse AM, and Mammen AL
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- Adult, Animals, Apolipoproteins A metabolism, Biopsy, Calcium-Calmodulin-Dependent Protein Kinase Type 1 metabolism, Cell Adhesion Molecules metabolism, Cell Culture Techniques, Dermatomyositis genetics, Early Growth Response Transcription Factors metabolism, Female, Humans, Hydroxymethylglutaryl CoA Reductases metabolism, Interleukin-8 metabolism, Machine Learning, Male, Mice, Mucoproteins metabolism, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Myositis pathology, Polymyositis genetics, Transcriptome, Autoimmune Diseases genetics, Muscular Diseases genetics, Myositis genetics, Myositis, Inclusion Body genetics
- Abstract
Objectives: Myositis is a heterogeneous family of diseases that includes dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM), inclusion body myositis (IBM), polymyositis and overlap myositis. Additional subtypes of myositis can be defined by the presence of myositis-specific autoantibodies (MSAs). The purpose of this study was to define unique gene expression profiles in muscle biopsies from patients with MSA-positive DM, AS and IMNM as well as IBM., Methods: RNA-seq was performed on muscle biopsies from 119 myositis patients with IBM or defined MSAs and 20 controls. Machine learning algorithms were trained on transcriptomic data and recursive feature elimination was used to determine which genes were most useful for classifying muscle biopsies into each type and MSA-defined subtype of myositis., Results: The support vector machine learning algorithm classified the muscle biopsies with >90% accuracy. Recursive feature elimination identified genes that are most useful to the machine learning algorithm and that are only overexpressed in one type of myositis. For example, CAMK1G (calcium/calmodulin-dependent protein kinase IG), EGR4 (early growth response protein 4) and CXCL8 (interleukin 8) are highly expressed in AS but not in DM or other types of myositis. Using the same computational approach, we also identified genes that are uniquely overexpressed in different MSA-defined subtypes. These included apolipoprotein A4 (APOA4), which is only expressed in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) myopathy, and MADCAM1 (mucosal vascular addressin cell adhesion molecule 1), which is only expressed in anti-Mi2-positive DM., Conclusions: Unique gene expression profiles in muscle biopsies from patients with MSA-defined subtypes of myositis and IBM suggest that different pathological mechanisms underly muscle damage in each of these diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2020
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22. Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research.
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McCann LJ, Pilkington CA, Huber AM, Ravelli A, Appelbe D, Kirkham JJ, Williamson PR, Aggarwal A, Christopher-Stine L, Constantin T, Feldman BM, Lundberg I, Maillard S, Mathiesen P, Murphy R, Pachman LM, Reed AM, Rider LG, van Royen-Kerkof A, Russo R, Spinty S, Wedderburn LR, and Beresford MW
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- Adolescent, Child, Consensus, Delphi Technique, Humans, Research, Data Collection methods, Databases, Factual, Dermatomyositis diagnosis
- Abstract
Objectives: This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres., Methods: A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation., Results: A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter., Conclusions: Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases., Competing Interests: Competing interests: IEL has research grants from Astra Zeneca and Bristol Myers Squibb and has served on advisory board for Bristol Myers Squibb., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2018
- Full Text
- View/download PDF
23. Thigh muscle MRI in immune-mediated necrotising myopathy: extensive oedema, early muscle damage and role of anti-SRP autoantibodies as a marker of severity.
- Author
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Pinal-Fernandez I, Casal-Dominguez M, Carrino JA, Lahouti AH, Basharat P, Albayda J, Paik JJ, Ahlawat S, Danoff SK, Lloyd TE, Mammen AL, and Christopher-Stine L
- Subjects
- Adiposity, Adult, Aged, Atrophy diagnostic imaging, Biomarkers blood, Dermatomyositis diagnostic imaging, Female, Humans, Hydroxymethylglutaryl CoA Reductases immunology, Male, Middle Aged, Muscle, Skeletal diagnostic imaging, Muscular Diseases blood, Muscular Diseases immunology, Myositis, Inclusion Body diagnostic imaging, Necrosis blood, Necrosis diagnostic imaging, Necrosis immunology, Polymyositis diagnostic imaging, Predictive Value of Tests, Severity of Illness Index, Thigh, Antibodies blood, Edema diagnostic imaging, Magnetic Resonance Imaging, Muscle, Skeletal pathology, Muscular Diseases diagnostic imaging, Signal Recognition Particle immunology
- Abstract
Objectives: The aims of this study were to define the pattern of muscle involvement in patients with immune-mediated necrotising myopathy (IMNM) relative to those with other inflammatory myopathies and to compare patients with IMNM with different autoantibodies., Methods: All Johns Hopkins Myositis Longitudinal Cohort subjects with a thigh MRI (tMRI) who fulfilled criteria for IMNM, dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) or clinically amyopathic DM (CADM) were included in the study. Muscles were assessed for intramuscular and fascial oedema, atrophy and fatty replacement. Disease subgroups were compared using univariate and multivariate analyses. Patients with IMNM with anti-signal recognition particle (SRP) autoantibodies were compared with those with IMNM with anti-HMG-CoA reductase (HMGCR) autoantibodies., Results: The study included 666 subjects (101 IMNM, 176 PM, 219 DM, 17 CADM and 153 IBM). Compared with DM or PM, IMNM was characterised by a higher proportion of thigh muscles with oedema, atrophy and fatty replacement (p<0.01). Patients with IMNM with anti-SRP had more atrophy (19%, p=0.003) and fatty replacement (18%, p=0.04) than those with anti-HMGCR. In IMNM, muscle abnormalities were especially common in the lateral rotator and gluteal groups. Fascial involvement was most widespread in DM. Fatty replacement of muscle tissue began early during the course of disease in IMNM and the other groups. An optimal combination of tMRI features had only a 55% positive predictive value for diagnosing IMNM., Conclusions: Compared with patients with DM or PM, IMNM is characterised by more widespread muscle involvement. Anti-SRP-positive patients have more severe muscle involvement than anti-HMGCR-positive patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
- Published
- 2017
- Full Text
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24. PUF60: a prominent new target of the autoimmune response in dermatomyositis and Sjögren's syndrome.
- Author
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Fiorentino DF, Presby M, Baer AN, Petri M, Rieger KE, Soloski M, Rosen A, Mammen AL, Christopher-Stine L, and Casciola-Rosen L
- Subjects
- Adult, Aged, Autoantigens immunology, Autoimmunity, Biomarkers blood, Case-Control Studies, Female, Humans, Male, Middle Aged, Salivary Glands immunology, Skin immunology, Autoantibodies blood, Dermatomyositis immunology, RNA Splicing Factors immunology, Repressor Proteins immunology, Sjogren's Syndrome immunology
- Abstract
Objectives: Autoantibodies are used clinically to phenotype and subset patients with autoimmune rheumatic diseases. We detected a novel 60 kDa autoantibody specificity by immunoblotting using a dermatomyositis (DM) patient's serum. Our objective was to identify the targeted autoantigen and to evaluate disease specificity and clinical significance of this new autoantibody., Methods: A new 60 kDa specificity was detected by immunoblotting HeLa cell lysates. The targeted autoantigen was identified as poly(U)-binding-splicing factor 60 kDa (PUF60) using (i) a human protein array and (ii) two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing. Anti-PUF60 antibodies were assayed by ELISA using sera from patients with primary Sjögren's syndrome (SS; n=84), systemic lupus erythematosus (SLE; n=71), DM (n=267), polymyositis (n=45), inclusion body myositis (n=45) and healthy controls (n=38)., Results: PUF60 was identified as a new autoantigen. Anti-PUF60 antibodies were present in 25/84 (30%) patients with SS, 6/71 (8.5%) patients with SLE and 2/38 (5.0%) control subjects (SS vs controls, p=0.002; SLE vs controls, p=0.711). Anti-PUF60 antibodies were present in 48/267 (18.0%) patients with DM versus 4/45 (8.9%) and 5/45 (11.1%) patients with inclusion body myositis and polymyositis, respectively. The antibody was significantly associated with anti-Ro52 antibodies, rheumatoid factor and hyperglobulinemia in the patients with primary SS. In patients with DM, the antibody was associated with anti-transcription intermediary factor 1 gamma seropositivity and Caucasian race., Conclusions: PUF60 represents a novel autoantigen in patients with SS and DM. PUF60 antibodies are associated with distinct clinical features and different immune responses in different diseases., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
- Published
- 2016
- Full Text
- View/download PDF
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