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39 results on '"Lahey, Lauren J."'

10. Identification of anticitrullinated protein antibody reactivities in a subset of anti-CCP-negative rheumatoid arthritis: association with cigarette smoking and HLA-DRB1 ‘shared epitope’ alleles

Author

Wagner, Catriona A, Sokolove, Jeremy, Lahey, Lauren J, Bengtsson, Camilla, Saevarsdottir, Saedis, Alfredsson, Lars, Delanoy, Michelle, Lindstrom, Tamsin M, Walker, Roger P, Bromberg, Reuven, Chandra, Piyanka E, Binder, Steven R, Klareskog, Lars, and Robinson, William H

Published
2015
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17. Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA)

Author

Hughes-Austin, Jan M, Deane, Kevin D, Derber, Lezlie A, Kolfenbach, Jason R, Zerbe, Gary O, Sokolove, Jeremy, Lahey, Lauren J, Weisman, Michael H, Buckner, Jane H, Mikuls, Ted R, OʼDell, James R, Keating, Richard M, Gregersen, Peter K, Robinson, William H, Holers, V Michael, and Norris, Jill M

Published
2013
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19. Antibody Responses to Citrullinated and Non-Citrullinated Antigens in the Sputum of Subjects with and At-Risk for Rheumatoid Arthritis

Author

Demoruelle, M. Kristen, Bowers, Emily, Lahey, Lauren J., Sokolove, Jeremy, Purmalek, Monica, Seto, Nickie L., Weisman, Michael H., Norris, Jill M., Kaplan, Mariana J., Holers, V. Michael, Robinson, William H., and Deane, Kevin D.

Subjects
Adult, Male, Sputum, Middle Aged, Autoantigens, Extracellular Traps, Peptides, Cyclic, Article, Arthritis, Rheumatoid, Young Adult, Case-Control Studies, Antibody Formation, Humans, Citrullination, Female, Prospective Studies, Aged, Autoantibodies
Abstract

The location and mechanisms involved in the initial generation of autoantibodies to citrullinated and noncitrullinated proteins/peptides during the natural history of rheumatoid arthritis (RA) development is incompletely understood. This study sought to explore individual antibody responses to citrullinated and noncitrullinated proteins/peptides in the sputum and associations with neutrophil extracellular traps (NETs) in subjects at risk for the future development of RA.Serum and sputum samples were obtained from 41 RA-free subjects who were considered at risk for the development of RA based on familial or serologic risk factors, from 20 subjects classified as having RA, and from 22 healthy control subjects. Samples were evaluated using a bead-based array for IgG reactivity to 29 citrullinated proteins/peptides and 21 noncitrullinated proteins/peptides. Cutoff levels for antibody positivity were established in a separate control group. NET levels in the sputum were measured using sandwich enzyme-linked immunosorbent assays that quantitate DNA-myeloperoxidase and DNA-neutrophil elastase complexes.In at-risk subjects, antibody responses to the citrullinated forms of fibrinogen, apolipoprotein E, and fibronectin were highly prevalent. The most citrulline-specific antibodies in the sputum of at-risk subjects were those to fibrinogen, vimentin, and peptides of fibrinogen A and apolipoprotein A1. Patterns of sputum autoantibody positivity differed between at-risk subjects and subjects with RA. In at-risk subjects, increasing sputum NET levels significantly correlated with several citrullinated and some noncitrullinated antibody reactivities.These findings suggest that sputum antibody reactivity to particular citrullinated and noncitrullinated proteins/peptides is specific for RA and for subjects at risk of RA, and the association of these proteins/peptides with NETs may be a key feature of early RA-related autoimmunity in the lung. These results further support the hypothesis that the lung plays a role in early RA-related autoimmunity.

Published
2018

21. Antibody Responses to Citrullinated and Noncitrullinated Antigens in the Sputum of Subjects With Rheumatoid Arthritis and Subjects at Risk for Development of Rheumatoid Arthritis

Author

Demoruelle, M. Kristen, primary, Bowers, Emily, additional, Lahey, Lauren J., additional, Sokolove, Jeremy, additional, Purmalek, Monica, additional, Seto, Nickie L., additional, Weisman, Michael H., additional, Norris, Jill M., additional, Kaplan, Mariana J., additional, Holers, V. Michael, additional, Robinson, William H., additional, and Deane, Kevin D., additional

Published
2018
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22. Circulating plasmablasts are elevated and produce pathogenic anti-endothelial cell autoantibodies in idiopathic pulmonary arterial hypertension

Author

Blum, Lisa K., primary, Cao, Richard R.L., additional, Sweatt, Andrew J., additional, Bill, Matthew, additional, Lahey, Lauren J., additional, Hsi, Andrew C., additional, Lee, Casey S., additional, Kongpachith, Sarah, additional, Ju, Chia-Hsin, additional, Mao, Rong, additional, Wong, Heidi H., additional, Nicolls, Mark R., additional, Zamanian, Roham T., additional, and Robinson, William H., additional

Published
2018
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23. IgA Plasmablasts are Elevated in Subjects At Risk for Future Rheumatoid Arthritis

Author

Kinslow, Jennifer D., Blum, Lisa K., Deane, Kevin D., Demoruelle, M. Kristen, Okamoto, Yuko, Parish, Mark, Kongpachith, Sarah, Lahey, Lauren J., Norris, Jill M., Robinson, William H., and Holers, V. Michael

Subjects
Arthritis, Rheumatoid, Immunoglobulin M, Rheumatoid Factor, Immunoglobulin G, Humans, Article, Immunoglobulin A
Published
2016

24. Phenome‐Wide Association Study of Autoantibodies to Citrullinated and Noncitrullinated Epitopes in Rheumatoid Arthritis

Author

Liao, Katherine P., primary, Sparks, Jeffrey A., additional, Hejblum, Boris P., additional, Kuo, I‐Hsin, additional, Cui, Jing, additional, Lahey, Lauren J., additional, Cagan, Andrew, additional, Gainer, Vivian S., additional, Liu, Weidong, additional, Cai, T. Tony, additional, Sokolove, Jeremy, additional, and Cai, Tianxi, additional

Published
2017
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25. Local Joint inflammation and histone citrullination in a murine model of the transition from preclinical autoimmunity to inflammatory arthritis

Author

Sohn, Dong Hyun, Rhodes, Christopher, Onuma, Kazuhiro, Zhao, Xiaoyan, Sharpe, Orr, Gazitt, Tal, Shiao, Rani, Fert-Bober, Justyna, Cheng, Danye, Lahey, Lauren J., Wong, Heidi H., Van Eyk, Jennifer, Robinson, William H., and Sokolove, Jeremy

Subjects
Inflammation, Proteomics, Autoimmunity, Antigen-Antibody Complex, Article, Arthritis, Rheumatoid, Histones, Disease Models, Animal, Disease Progression, Animals, Citrulline, Humans, Joints, Autoantibodies
Abstract

Anti-citrullinated protein antibodies (ACPAs) are characteristic of rheumatoid arthritis (RA). However, their presence years before the onset of clinical RA is perplexing. Although multiple putative citrullinated antigens have been identified, no studies have demonstrated the specific capacity of these antigens to initiate inflammatory arthritis. This study was undertaken to recapitulate the transition from preclinical to clinical RA and to demonstrate the capacity of local citrullination to facilitate this transition.We performed proteomic analysis of activated human neutrophils to identify citrullinated proteins, including those targeted as part of the RA immune response. Using enzyme-linked immunosorbent assay, we compared RA and osteoarthritis synovial fluid for levels of citrullinated histone H2B and its immune complex. Using macrophage activation assays, we assessed the effect of histone citrullination on immunostimulatory capacity and evaluated the stimulatory capacity of native and citrullinated H2B immune complexes. Finally, we assessed the potential for anti-citrullinated H2B antibodies to mediate arthritis in vivo.We identified robust targeting of neutrophil-derived citrullinated histones by the ACPA immune response. More than 90% of the RA patients had anti-citrullinated H2B antibodies. Histone citrullination increased innate immunostimulatory capacity, and immune complexes containing citrullinated histones activated macrophage cytokine production and propagated neutrophil activation. Finally, we demonstrated that immunization with H2B was arthritogenic, but only in the setting of underlying articular inflammation.Our findings indicate that citrullinated histones, specifically citrullinated H2B, are an antigenic target of the ACPA immune response. Furthermore, local generation of citrullinated antigen during low-grade articular inflammation provides a mechanistic model for the conversion from preclinical autoimmunity to inflammatory arthritis.

Published
2014

28. Increased inflammation and disease activity among current cigarette smokers with rheumatoid arthritis: a cross-sectional analysis of US veterans

Author

Sokolove, Jeremy, primary, Wagner, Catriona A., additional, Lahey, Lauren J., additional, Sayles, Harlan, additional, Duryee, Michael J., additional, Reimold, Andreas M., additional, Kerr, Gail, additional, Robinson, William H., additional, Cannon, Grant W., additional, Thiele, Geoffrey M., additional, and Mikuls, Ted R., additional

Published
2016
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29. Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

Author

Lahey, Lauren J., primary, Panas, Michael W., additional, Mao, Rong, additional, Delanoy, Michelle, additional, Flanagan, John J., additional, Binder, Steven R., additional, Rebman, Alison W., additional, Montoya, Jose G., additional, Soloski, Mark J., additional, Steere, Allen C., additional, Dattwyler, Raymond J., additional, Arnaboldi, Paul M., additional, Aucott, John N., additional, and Robinson, William H., additional

Published
2015
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32. Identification of anticitrullinated protein antibody reactivities in a subset of anti-CCP-negative rheumatoid arthritis: association with cigarette smoking and HLA-DRB1 ‘shared epitope’ alleles

Author

Wagner, Catriona A, primary, Sokolove, Jeremy, additional, Lahey, Lauren J, additional, Bengtsson, Camilla, additional, Saevarsdottir, Saedis, additional, Alfredsson, Lars, additional, Delanoy, Michelle, additional, Lindstrom, Tamsin M, additional, Walker, Roger P, additional, Bromberg, Reuven, additional, Chandra, Piyanka E, additional, Binder, Steven R, additional, Klareskog, Lars, additional, and Robinson, William H, additional

Published
2013
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33. Response to 'Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4' - authors' reply

Author

Sohn, Dong Hyun, primary, Sokolove, Jeremy, additional, Sharpe, Orr, additional, Erhart, Jennifer C, additional, Chandra, Piyanka E, additional, Lahey, Lauren J, additional, Lindstrom, Tamsin M, additional, Hwang, Inyong, additional, Boyer, Katherine A, additional, Andriacchi, Thomas P, additional, and Robinson, William H, additional

Published
2012
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34. Correction: Autoantibody Epitope Spreading in the Pre-Clinical Phase Predicts Progression to Rheumatoid Arthritis

Author

Sokolove, Jeremy, primary, Bromberg, Reuven, additional, Deane, Kevin D., additional, Lahey, Lauren J., additional, Derber, Lezlie A., additional, Chandra, Piyanka E., additional, Edison, Jess D., additional, Gilliland, William R., additional, Tibshirani, Robert J., additional, Norris, Jill M., additional, Holers, V. Michael, additional, and Robinson, William H., additional

Published
2012
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35. Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA)

Author

Hughes-Austin, Jan M, primary, Deane, Kevin D, additional, Derber, Lezlie A, additional, Kolfenbach, Jason R, additional, Zerbe, Gary O, additional, Sokolove, Jeremy, additional, Lahey, Lauren J, additional, Weisman, Michael H, additional, Buckner, Jane H, additional, Mikuls, Ted R, additional, O'Dell, James R, additional, Keating, Richard M, additional, Gregersen, Peter K, additional, Robinson, William H, additional, Holers, V Michael, additional, and Norris, Jill M, additional

Published
2012
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36. Autoantibody Epitope Spreading in the Pre-Clinical Phase Predicts Progression to Rheumatoid Arthritis

Author

Sokolove, Jeremy, primary, Bromberg, Reuven, additional, Deane, Kevin D., additional, Lahey, Lauren J., additional, Derber, Lezlie A., additional, Chandra, Piyanka E., additional, Edison, Jess D., additional, Gilliland, William R., additional, Tibshirani, Robert J., additional, Norris, Jill M., additional, Holers, V. Michael, additional, and Robinson, William H., additional

Published
2012
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37. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4

Author

Sohn, Dong, primary, Sokolove, Jeremy, additional, Sharpe, Orr, additional, Erhart, Jennifer C, additional, Chandra, Piyanka E, additional, Lahey, Lauren J, additional, Lindstrom, Tamsin M, additional, Hwang, Inyong, additional, Boyer, Katherine A, additional, Andriacchi, Thomas P, additional, and Robinson, William H, additional

Published
2012
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38. Phenome‐Wide Association Study of Autoantibodies to Citrullinated and Noncitrullinated Epitopes in Rheumatoid Arthritis

Author

Liao, Katherine P., Sparks, Jeffrey A., Hejblum, Boris P., Kuo, I‐Hsin, Cui, Jing, Lahey, Lauren J., Cagan, Andrew, Gainer, Vivian S., Liu, Weidong, Cai, T. Tony, Sokolove, Jeremy, and Cai, Tianxi

Subjects
Rheumatoid Arthritis
Abstract

Objective: Patients with rheumatoid arthritis (RA) develop autoantibodies against a spectrum of antigens, but the clinical significance of these autoantibodies is unclear. Using a phenome‐wide association study (PheWAS) approach, we examined the association between autoantibodies and clinical subphenotypes of RA. Methods: This study was conducted in a cohort of RA patients identified from the electronic medical records (EMRs) of 2 tertiary care centers. Using a published multiplex bead assay, we measured 36 autoantibodies targeting epitopes implicated in RA. We extracted all International Classification of Diseases, Ninth Revision (ICD‐9) codes for each subject and grouped them into disease categories (PheWAS codes), using a published method. We tested for the association of each autoantibody (grouped by the targeted protein) with PheWAS codes. To determine significant associations (at a false discovery rate [FDR] of ≤0.1), we reviewed the medical records of 50 patients with each PheWAS code to determine positive predictive values (PPVs). Results: We studied 1,006 RA patients; the mean ± SD age of the patients was 61.0 ± 12.9 years, and 79.0% were female. A total of 3,568 unique ICD‐9 codes were grouped into 625 PheWAS codes; the 206 PheWAS codes with a prevalence of ≥3% were studied. Using the PheWAS method, we identified 24 significant associations of autoantibodies to epitopes at an FDR of ≤0.1. The associations that were strongest and had the highest PPV for the PheWAS code were autoantibodies against fibronectin and obesity (P = 6.1 × 10−4, PPV 100%), and that between fibrinogen and pneumonopathy (P = 2.7 × 10−4, PPV 96%). Pneumonopathy codes included diagnoses for cryptogenic organizing pneumonia and obliterative bronchiolitis. Conclusion: We demonstrated application of a bioinformatics method, the PheWAS, to screen for the clinical significance of RA‐related autoantibodies. Using the PheWAS approach, we identified potentially significant links between variations in the levels of autoantibodies and comorbidities of interest in RA.

Published
2017
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39. Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferiInfection in Early Lyme Disease

Author

Lahey, Lauren J., Panas, Michael W., Mao, Rong, Delanoy, Michelle, Flanagan, John J., Binder, Steven R., Rebman, Alison W., Montoya, Jose G., Soloski, Mark J., Steere, Allen C., Dattwyler, Raymond J., Arnaboldi, Paul M., Aucott, John N., and Robinson, William H.

Abstract

ABSTRACTThe current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferisurface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P< 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferiinfection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease.

Published
2015
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