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The immune cell landscape in kidneys of lupus nephritis patients

Arnon Arazi, Deepak A. Rao, Celine C. Berthier, Anne Davidson, Yanyan Liu, Paul J. Hoover, Adam Chicoine, Thomas M. Eisenhaure, A. Helena Jonsson, Shuqiang Li, David J. Lieb, Edward P. Browne, Akiko Noma, Danielle Sutherby, Scott Steelman, Dawn E. Smilek, Patti Tosta, William Apruzzese, Elena Massarotti, Maria Dall’Era, Meyeon Park, Diane L. Kamen, Richard A. Furie, Fernanda Payan-Schober, Jill P. Buyon, Michelle A. Petri, Chaim Putterman, Kenneth C. Kalunian, E. Steve Woodle, James A. Lederer, David A. Hildeman, Chad Nusbaum, David Wofsy, Matthias Kretzler, Jennifer H. Anolik, Michael B. Brenner, the Accelerating Medicines Partnership in RA/SLE network, Nir Hacohen, Betty Diamond
doi: https://doi.org/10.1101/363051
Arnon Arazi
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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Deepak A. Rao
2Division of Rheumatology, Allergy, Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA 02115
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Celine C. Berthier
3Internal Medicine, Department of Nephrology, University of Michigan, Ann Arbor, MI, USA 48109
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Anne Davidson
4Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY 11030
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Yanyan Liu
2Division of Rheumatology, Allergy, Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA 02115
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Paul J. Hoover
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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Adam Chicoine
2Division of Rheumatology, Allergy, Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA 02115
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Thomas M. Eisenhaure
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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A. Helena Jonsson
2Division of Rheumatology, Allergy, Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA 02115
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Shuqiang Li
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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David J. Lieb
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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Edward P. Browne
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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Akiko Noma
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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Danielle Sutherby
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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Scott Steelman
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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Dawn E. Smilek
5Lupus Nephritis Trials Network, University of California San Francisco, San Francisco, CA 94107
6Immune Tolerance Network, University of California San Francisco, San Francisco, CA 94107
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Patti Tosta
5Lupus Nephritis Trials Network, University of California San Francisco, San Francisco, CA 94107
6Immune Tolerance Network, University of California San Francisco, San Francisco, CA 94107
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William Apruzzese
2Division of Rheumatology, Allergy, Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA 02115
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Elena Massarotti
2Division of Rheumatology, Allergy, Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA 02115
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Maria Dall’Era
7Rheumatology Division, University of California San Francisco, San Francisco, CA 94107
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Meyeon Park
8Division of Nephrology, University of California, San Francisco, San Francisco, CA 94107
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Diane L. Kamen
9Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425
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Richard A. Furie
10Division of Rheumatology, Northwell Health, Great Neck, NY 11021
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Fernanda Payan-Schober
11University of North Carolina Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, Chapel Hill, NC, 27599
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Jill P. Buyon
12Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, 10016
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Michelle A. Petri
13Division of Rheumatology, Johns Hopkins University, Baltimore, MD, 21287
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Chaim Putterman
14Division of Rheumatology and Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, 10461
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Kenneth C. Kalunian
15University of California San Diego School of Medicine, La Jolla, California, 92093
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E. Steve Woodle
16Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45257
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James A. Lederer
17Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
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David A. Hildeman
18Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45257
19Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229
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Chad Nusbaum
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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David Wofsy
7Rheumatology Division, University of California San Francisco, San Francisco, CA 94107
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Matthias Kretzler
3Internal Medicine, Department of Nephrology, University of Michigan, Ann Arbor, MI, USA 48109
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Jennifer H. Anolik
20Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, NY 14642
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Michael B. Brenner
2Division of Rheumatology, Allergy, Immunology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA 02115
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Nir Hacohen
1Broad Institute of MIT and Harvard, Cambridge MA 02142
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Betty Diamond
4Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY 11030
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ABSTRACT

Lupus nephritis is a potentially fatal autoimmune disease, whose current treatment is ineffective and often toxic. To gain insights into disease mechanisms, we analyzed kidney samples from lupus nephritis patients and healthy controls using single-cell RNA-seq. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid, T, NK and B cells, demonstrating both pro-inflammatory and resolving responses. We found evidence of local activation of B cells correlated with an age-associated B cell signature, and of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, pointing to potential therapeutic targets. Gene expression of immune cells in urine and kidney was highly correlated, suggesting urine may be a surrogate for kidney biopsies. Our results provide a first comprehensive view of the complex network of leukocytes active in lupus nephritis kidneys.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 07, 2018.
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The immune cell landscape in kidneys of lupus nephritis patients
Arnon Arazi, Deepak A. Rao, Celine C. Berthier, Anne Davidson, Yanyan Liu, Paul J. Hoover, Adam Chicoine, Thomas M. Eisenhaure, A. Helena Jonsson, Shuqiang Li, David J. Lieb, Edward P. Browne, Akiko Noma, Danielle Sutherby, Scott Steelman, Dawn E. Smilek, Patti Tosta, William Apruzzese, Elena Massarotti, Maria Dall’Era, Meyeon Park, Diane L. Kamen, Richard A. Furie, Fernanda Payan-Schober, Jill P. Buyon, Michelle A. Petri, Chaim Putterman, Kenneth C. Kalunian, E. Steve Woodle, James A. Lederer, David A. Hildeman, Chad Nusbaum, David Wofsy, Matthias Kretzler, Jennifer H. Anolik, Michael B. Brenner, the Accelerating Medicines Partnership in RA/SLE network, Nir Hacohen, Betty Diamond
bioRxiv 363051; doi: https://doi.org/10.1101/363051
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The immune cell landscape in kidneys of lupus nephritis patients
Arnon Arazi, Deepak A. Rao, Celine C. Berthier, Anne Davidson, Yanyan Liu, Paul J. Hoover, Adam Chicoine, Thomas M. Eisenhaure, A. Helena Jonsson, Shuqiang Li, David J. Lieb, Edward P. Browne, Akiko Noma, Danielle Sutherby, Scott Steelman, Dawn E. Smilek, Patti Tosta, William Apruzzese, Elena Massarotti, Maria Dall’Era, Meyeon Park, Diane L. Kamen, Richard A. Furie, Fernanda Payan-Schober, Jill P. Buyon, Michelle A. Petri, Chaim Putterman, Kenneth C. Kalunian, E. Steve Woodle, James A. Lederer, David A. Hildeman, Chad Nusbaum, David Wofsy, Matthias Kretzler, Jennifer H. Anolik, Michael B. Brenner, the Accelerating Medicines Partnership in RA/SLE network, Nir Hacohen, Betty Diamond
bioRxiv 363051; doi: https://doi.org/10.1101/363051

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