Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq
Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/78550 |
| _version_ | 1811213926665289728 |
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| author | Sara E Vazquez Sabrina A Mann Aaron Bodansky Andrew F Kung Zoe Quandt Elise MN Ferré Nils Landegren Daniel Eriksson Paul Bastard Shen-Ying Zhang Jamin Liu Anthea Mitchell Irina Proekt David Yu Caleigh Mandel-Brehm Chung-Yu Wang Brenda Miao Gavin Sowa Kelsey Zorn Alice Y Chan Veronica M Tagi Chisato Shimizu Adriana Tremoulet Kara Lynch Michael R Wilson Olle Kämpe Kerry Dobbs Ottavia M Delmonte Rosa Bacchetta Luigi D Notarangelo Jane C Burns Jean-Laurent Casanova Michail S Lionakis Troy R Torgerson Mark S Anderson Joseph L DeRisi |
| author_facet | Sara E Vazquez Sabrina A Mann Aaron Bodansky Andrew F Kung Zoe Quandt Elise MN Ferré Nils Landegren Daniel Eriksson Paul Bastard Shen-Ying Zhang Jamin Liu Anthea Mitchell Irina Proekt David Yu Caleigh Mandel-Brehm Chung-Yu Wang Brenda Miao Gavin Sowa Kelsey Zorn Alice Y Chan Veronica M Tagi Chisato Shimizu Adriana Tremoulet Kara Lynch Michael R Wilson Olle Kämpe Kerry Dobbs Ottavia M Delmonte Rosa Bacchetta Luigi D Notarangelo Jane C Burns Jean-Laurent Casanova Michail S Lionakis Troy R Torgerson Mark S Anderson Joseph L DeRisi |
| author_sort | Sara E Vazquez |
| collection | DOAJ |
| description | Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies. |
| first_indexed | 2024-04-12T05:54:31Z |
| format | Article |
| id | doaj.art-fc84c5436a6d424088e17402a161e72b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T05:54:31Z |
| publishDate | 2022-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fc84c5436a6d424088e17402a161e72b2022-12-22T03:45:11ZengeLife Sciences Publications LtdeLife2050-084X2022-10-011110.7554/eLife.78550Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seqSara E Vazquez0https://orcid.org/0000-0002-0601-7001Sabrina A Mann1https://orcid.org/0000-0002-4970-1073Aaron Bodansky2https://orcid.org/0000-0001-8943-8233Andrew F Kung3Zoe Quandt4Elise MN Ferré5Nils Landegren6https://orcid.org/0000-0002-6163-9540Daniel Eriksson7https://orcid.org/0000-0001-5473-3312Paul Bastard8Shen-Ying Zhang9Jamin Liu10Anthea Mitchell11Irina Proekt12David Yu13Caleigh Mandel-Brehm14Chung-Yu Wang15Brenda Miao16https://orcid.org/0000-0002-3393-9837Gavin Sowa17https://orcid.org/0000-0002-2089-8116Kelsey Zorn18Alice Y Chan19Veronica M Tagi20Chisato Shimizu21Adriana Tremoulet22Kara Lynch23Michael R Wilson24https://orcid.org/0000-0002-8705-5084Olle Kämpe25https://orcid.org/0000-0001-6091-9914Kerry Dobbs26https://orcid.org/0000-0002-3432-3137Ottavia M Delmonte27Rosa Bacchetta28Luigi D Notarangelo29Jane C Burns30Jean-Laurent Casanova31Michail S Lionakis32Troy R Torgerson33https://orcid.org/0000-0003-3489-5036Mark S Anderson34https://orcid.org/0000-0002-3093-4758Joseph L DeRisi35https://orcid.org/0000-0002-4611-9205Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Diabetes Center, University of California, San Francisco, San Francisco, United States; School of Medicine, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Chan Zuckerberg Biohub, San Francisco, United StatesDepartment of Pediatric Critical Care Medicine, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesDiabetes Center, University of California, San Francisco, San Francisco, United States; Department of Medicine, University of California, San Francisco, San Francisco, United StatesFungal Pathogenesis Unit, Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United StatesDepartment of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden; Science for life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, SwedenDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Centre for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, SwedenSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, United States; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; Imagine Institute, University of Paris, Paris, France; Department of Pediatrics, Necker Hospital for Sick Children, Paris, FranceSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, United States; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; Imagine Institute, University of Paris, Paris, FranceDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Chan Zuckerberg Biohub, San Francisco, United StatesDiabetes Center, University of California, San Francisco, San Francisco, United StatesDiabetes Center, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Chan Zuckerberg Biohub, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesSchool of Medicine, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United StatesDepartment of Pediatrics, Division of Pediatric Allergy, Immunology, Bone and Marrow Transplantation, Division of Pediatric Rheumatology, University of California, San Francisco, San Francisco, United StatesDivision of Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, United StatesKawasaki Disease Research Center, Rady Children’s Hospital and Department of Pediatrics, University of California, San Diego, La Jolla, United StatesKawasaki Disease Research Center, Rady Children’s Hospital and Department of Pediatrics, University of California, San Diego, La Jolla, United StatesDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, United States; Zuckerberg San Francisco General, San Francisco, United StatesWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, United StatesDepartment of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden; Department of Clinical Science and KG Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway; Center of Molecular Medicine, and Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, SwedenLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United StatesLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United StatesDivision of Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, United StatesLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United StatesKawasaki Disease Research Center, Rady Children’s Hospital and Department of Pediatrics, University of California, San Diego, La Jolla, United StatesSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University, New York, United States; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; Imagine Institute, University of Paris, Paris, France; Department of Pediatrics, Necker Hospital for Sick Children, Paris, France; Howard Hughes Medical Institute, New York, United StatesFungal Pathogenesis Unit, Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United StatesSeattle Children's Research Institute, Seattle, United States; Department of Pediatrics, University of Washington, Seattle, United StatesDiabetes Center, University of California, San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Chan Zuckerberg Biohub, San Francisco, United StatesPhage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.https://elifesciences.org/articles/78550PhIP-seqautoantibodyautoantigenCOVID-19APS1IPEX |
| spellingShingle | Sara E Vazquez Sabrina A Mann Aaron Bodansky Andrew F Kung Zoe Quandt Elise MN Ferré Nils Landegren Daniel Eriksson Paul Bastard Shen-Ying Zhang Jamin Liu Anthea Mitchell Irina Proekt David Yu Caleigh Mandel-Brehm Chung-Yu Wang Brenda Miao Gavin Sowa Kelsey Zorn Alice Y Chan Veronica M Tagi Chisato Shimizu Adriana Tremoulet Kara Lynch Michael R Wilson Olle Kämpe Kerry Dobbs Ottavia M Delmonte Rosa Bacchetta Luigi D Notarangelo Jane C Burns Jean-Laurent Casanova Michail S Lionakis Troy R Torgerson Mark S Anderson Joseph L DeRisi Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq eLife PhIP-seq autoantibody autoantigen COVID-19 APS1 IPEX |
| title | Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq |
| title_full | Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq |
| title_fullStr | Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq |
| title_full_unstemmed | Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq |
| title_short | Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq |
| title_sort | autoantibody discovery across monogenic acquired and covid 19 associated autoimmunity with scalable phip seq |
| topic | PhIP-seq autoantibody autoantigen COVID-19 APS1 IPEX |
| url | https://elifesciences.org/articles/78550 |
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