Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis
Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by the...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01384/full |
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| author | Theresa L. Wampler Muskardin Theresa L. Wampler Muskardin Wei Fan Zhongbo Jin Mark A. Jensen Mark A. Jensen Jessica M. Dorschner Yogita Ghodke-Puranik Yogita Ghodke-Puranik Betty Dicke Danielle Vsetecka Kerry Wright Thomas Mason Scott Persellin Clement J. Michet John M. Davis Eric Matteson Timothy B. Niewold |
| author_facet | Theresa L. Wampler Muskardin Theresa L. Wampler Muskardin Wei Fan Zhongbo Jin Mark A. Jensen Mark A. Jensen Jessica M. Dorschner Yogita Ghodke-Puranik Yogita Ghodke-Puranik Betty Dicke Danielle Vsetecka Kerry Wright Thomas Mason Scott Persellin Clement J. Michet John M. Davis Eric Matteson Timothy B. Niewold |
| author_sort | Theresa L. Wampler Muskardin |
| collection | DOAJ |
| description | Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. In our previous work, RA patients who had either high IFNβ/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant: “T1IFN undetectable (T1IFN ND) or IFNβ/α >1.3” (n = 9) and “T1IFN detectable but IFNβ/α ≤ 1.3” (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself: “T1IFN ND,” “T1IFN detected and IFNβ/α ≤ 1.3,” and “IFNβ/α >1.3.” Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNβ/α >1.3 group were unlikely to express JAK1 and IFI27 (p < 0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤ 0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from nine patients. This pattern most strongly associated with the IFNβ/α>1.3 group. Differences in gene expression in monocytes among the groups suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. Additional transcripts enriched in NC cells of those in the T1IFN ND and IFNβ/α >1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi. |
| first_indexed | 2024-12-16T07:11:45Z |
| format | Article |
| id | doaj.art-d521672247904464a02dd07ba7908c20 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T07:11:45Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-d521672247904464a02dd07ba7908c202022-12-21T22:39:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01384517876Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid ArthritisTheresa L. Wampler Muskardin0Theresa L. Wampler Muskardin1Wei Fan2Zhongbo Jin3Mark A. Jensen4Mark A. Jensen5Jessica M. Dorschner6Yogita Ghodke-Puranik7Yogita Ghodke-Puranik8Betty Dicke9Danielle Vsetecka10Kerry Wright11Thomas Mason12Scott Persellin13Clement J. Michet14John M. Davis15Eric Matteson16Timothy B. Niewold17Department of Medicine, Colton Center for Autoimmunity, New York University School of Medicine, New York, NY, United StatesDivision of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY, United StatesDepartment of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United StatesDepartment of Medicine, Colton Center for Autoimmunity, New York University School of Medicine, New York, NY, United StatesDivision of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDepartment of Medicine, Colton Center for Autoimmunity, New York University School of Medicine, New York, NY, United StatesDivision of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United StatesDepartment of Medicine, Colton Center for Autoimmunity, New York University School of Medicine, New York, NY, United StatesPreviously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. In our previous work, RA patients who had either high IFNβ/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant: “T1IFN undetectable (T1IFN ND) or IFNβ/α >1.3” (n = 9) and “T1IFN detectable but IFNβ/α ≤ 1.3” (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself: “T1IFN ND,” “T1IFN detected and IFNβ/α ≤ 1.3,” and “IFNβ/α >1.3.” Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNβ/α >1.3 group were unlikely to express JAK1 and IFI27 (p < 0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤ 0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from nine patients. This pattern most strongly associated with the IFNβ/α>1.3 group. Differences in gene expression in monocytes among the groups suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. Additional transcripts enriched in NC cells of those in the T1IFN ND and IFNβ/α >1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi.https://www.frontiersin.org/article/10.3389/fimmu.2020.01384/fulltype I interferontumor necrosis factor-alphamonocytesingle cellrheumatoid arthritisjanus kinase 1 |
| spellingShingle | Theresa L. Wampler Muskardin Theresa L. Wampler Muskardin Wei Fan Zhongbo Jin Mark A. Jensen Mark A. Jensen Jessica M. Dorschner Yogita Ghodke-Puranik Yogita Ghodke-Puranik Betty Dicke Danielle Vsetecka Kerry Wright Thomas Mason Scott Persellin Clement J. Michet John M. Davis Eric Matteson Timothy B. Niewold Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis Frontiers in Immunology type I interferon tumor necrosis factor-alpha monocyte single cell rheumatoid arthritis janus kinase 1 |
| title | Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis |
| title_full | Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis |
| title_fullStr | Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis |
| title_full_unstemmed | Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis |
| title_short | Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis |
| title_sort | distinct single cell gene expression in peripheral blood monocytes correlates with tumor necrosis factor inhibitor treatment response groups defined by type i interferon in rheumatoid arthritis |
| topic | type I interferon tumor necrosis factor-alpha monocyte single cell rheumatoid arthritis janus kinase 1 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01384/full |
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