Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

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Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

Vazquez, Sara E. (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.;Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94118 USA.

Mann, Sabrina A. (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.;Chan Zuckerberg Biohub, San Francisco, CA 94118 USA.

Bodansky, Aaron (författare): Univ Calif San Francisco, Dept Pediat Crit Care Med, San Francisco, CA USA.

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Kung, Andrew F. (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.

Quandt, Zoe (författare): Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94118 USA.;Univ Calif San Francisco, Dept Med, San Francisco, CA USA.

Ferre, Elise M. N. (författare): Natl Inst Allergy & Infect Dis, NIH, Lab Clin Immunol & Microbiol, Fungal Pathogenesis Unit, Bethesda, MD USA.

Landegren, Nils, 1986- (författare): Karolinska Institutet,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden.

Eriksson, Daniel (författare): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Karolinska Inst, Ctr Mol Med, Dept Med, Stockholm, Sweden.

Bastard, Paul (författare): Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.;Necker Hosp Sick Children, Dept Pediat, Paris, France.

Zhang, Shen-Ying (författare): Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.

Liu, Jamin (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.;Univ Calif San Francisco, Berkeley Univ Calif, San Francisco Grad Program Bioengn, San Francisco, CA USA.

Mitchell, Anthea (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.;Chan Zuckerberg Biohub, San Francisco, CA 94118 USA.

Proekt, Irina (författare): Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94118 USA.

Yu, David (författare): Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94118 USA.

Mandel-Brehm, Caleigh (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.

Wang, Chung-Yu (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.;Chan Zuckerberg Biohub, San Francisco, CA 94118 USA.

Miao, Brenda (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.

Sowa, Gavin (författare): Univ Calif San Francisco, Sch Med, San Francisco, CA USA.

Zorn, Kelsey (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.

Chan, Alice Y. (författare): Univ Calif San Francisco, Dept Pediat, Div Pediat Allergy Immunol Bone & Marrow Transplan, Div Pediat Rheumatol, San Francisco, CA USA.

Tagi, Veronica M. (författare): Stanford Univ, Div Stem Cell Transplantat & Regenerat Med, Sch Med, Stanford, CA USA.

Shimizu, Chisato (författare): Univ Calif San Diego, Rady Childrens Hosp, Kawasaki Dis Res Ctr, La Jolla, CA USA.;Univ Calif San Diego, Dept Pediat, La Jolla, CA USA.

Tremoulet, Adriana (författare): Univ Calif San Diego, Rady Childrens Hosp, Kawasaki Dis Res Ctr, La Jolla, CA USA.;Univ Calif San Diego, Dept Pediat, La Jolla, CA USA.

Lynch, Kara (författare): Univ Calif San Francisco, Dept Lab Med, San Francisco, CA USA.;Zuckerberg San Francisco Gen, San Francisco, CA USA.

Wilson, Michael R. (författare): Univ Calif San Francisco, Weill Inst Neurosci, San Francisco, CA USA.

Kaempe, Olle (författare): Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden.;Univ Bergen, Dept Clin Sci, Bergen, Norway.;Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, Bergen, Norway.;Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.

Dobbs, Kerry (författare): NIAID, Lab Clin Immunol & Microbiol, NIH, Bethesda, MD USA.

Delmonte, Ottavia M. (författare): NIAID, Lab Clin Immunol & Microbiol, NIH, Bethesda, MD USA.

Bacchetta, Rosa (författare)

Notarangelo, Luigi D. (författare): NIAID, Lab Clin Immunol & Microbiol, NIH, Bethesda, MD USA.

Burns, Jane C. (författare)

Casanova, Jean-Laurent (författare): Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.;Necker Hosp Sick Children, Dept Pediat, Paris, France.;Howard Hughes Med Inst, New York, NY USA.

Lionakis, Michail S. (författare): Natl Inst Allergy & Infect Dis, NIH, Lab Clin Immunol & Microbiol, Fungal Pathogenesis Unit, Bethesda, MD USA.

Torgerson, Troy R. (författare): Seattle Childrens Res Inst, Seattle, WA USA.;Univ Washington, Dept Pediat, Seattle, WA USA.

Anderson, Mark S. (författare): Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94118 USA.

DeRisi, Joseph L. (författare): Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.;Chan Zuckerberg Biohub, San Francisco, CA 94118 USA.

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Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA;Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94118 USA.;Chan Zuckerberg Biohub, San Francisco, CA 94118 USA. (creator_code:org_t)

eLife Sciences Publications Ltd, 2022
2022
Engelska.
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11

Relaterad länk:: https://uu.diva-port... (primary) (Raw object); visa fler...; https://urn.kb.se/re...; https://doi.org/10.7...; http://kipublication...; visa färre...

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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.

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Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

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