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- Judith A James
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Joel M Guthridge
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Hua Chen
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Rufei Lu
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Rebecka L Bourn
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Krista Bean
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Melissa E Munroe
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Miles Smith
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Eliza Chakravarty
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Alan N Baer
- Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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- Ghaith Noaiseh
- Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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- Ann Parke
- Division of Rheumatic Diseases, University of Connecticut, Farmington, CT, USA
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- Karen Boyle
- Rho Federal Systems Division, Chapel Hill, NC, USA
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- Lynette Keyes-Elstein
- Rho Federal Systems Division, Chapel Hill, NC, USA
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- Andreea Coca
- Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
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- Tammy Utset
- Department of Medicine, University of Chicago, Chicago, IL, USA
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- Mark C Genovese
- Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA
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- Virginia Pascual
- Drukier Institute for Children’s Health, Weill Cornell Medicine, New York, NY, USA
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- Paul J Utz
- Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA
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- V. Michael Holers
- Division of Rheumatology, University of Colorado School of Medicine, Aurora,CO, USA
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- Kevin D Deane
- Division of Rheumatology, University of Colorado School of Medicine, Aurora,CO, USA
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- Kathy L Sivils
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Teresa Aberle
- Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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- Daniel J Wallace
- Department of Medicine, Cedars-Sinai Medical Center, West Hollywood, CA, USA
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- James McNamara
- Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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- Nathalie Franchimont
- Biogen, Cambridge, MA, USA
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- E. William St. Clair
- Division of Rheumatology and Immunology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
説明
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To address heterogeneity complicating primary SS (pSS) clinical trials, research and care by characterizing and clustering patients by their molecular phenotypes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>pSS patients met American–European Consensus Group classification criteria and had at least one systemic manifestation and stimulated salivary flow of ⩾0.1 ml/min. Correlated transcriptional modules were derived from gene expression microarray data from blood (n = 47 with appropriate samples). Patients were clustered based on this molecular information using an unbiased random forest modelling approach. In addition, multiplex, bead-based assays and ELISAs were used to assess 30 serum cytokines, chemokines and soluble receptors. Eleven autoantibodies, including anti-Ro/SSA and anti-La/SSB, were measured by Bio-Rad Bioplex 2200.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Transcriptional modules distinguished three clusters of pSS patients. Cluster 1 showed no significant elevation of IFN or inflammation modules. Cluster 2 showed strong IFN and inflammation modular network signatures, as well as high plasma protein levels of IP-10/CXCL10, MIG/CXCL9, BLyS (BAFF) and LIGHT. Cluster 3 samples exhibited moderately elevated IFN modules, but with suppressed inflammatory modules, increased IP-10/CXCL10 and B cell–attracting chemokine 1/CXCL13 and trends toward increased MIG/CXCL9, IL-1α, and IL-21. Anti-Ro/SSA and anti-La/SSB were present in all three clusters.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Molecular profiles encompassing IFN, inflammation and other signatures can be used to separate patients with pSS into distinct clusters. In the future, such profiles may inform patient selection for clinical trials and guide treatment decisions.</jats:p></jats:sec>
収録刊行物
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- Rheumatology
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Rheumatology 59 (4), 860-868, 2019-09-08
Oxford University Press (OUP)
