Autoantibody-positive healthy individuals with lower lupus risk display a unique immune endotype.

Adult Black or African American Antibodies, Antinuclear / immunology Female Humans Lupus Erythematosus, Systemic / immunology Lymphocyte Activation Male Signal Transduction / immunology T-Lymphocytes / immunology White People
ANA+ healthy Autoantibodies SLE T cells cytokines immune suppression race

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
12 2020
Historique:
received: 19 12 2019
revised: 01 04 2020
accepted: 15 04 2020
pubmed: 25 5 2020
medline: 18 3 2021
entrez: 25 5 2020
Statut: ppublish

Résumé

Autoimmune diseases comprise a spectrum of illnesses and are on the rise worldwide. Although antinuclear antibodies (ANAs) are detected in many autoimmune diseases, up to 20% of healthy women are ANA-positive (ANA+) and most will never develop clinical symptoms. Furthermore, disease transition is higher among ANA+ African Americans compared with ANA+ European Americans. We sought to determine the immune features that might define and prevent transition to clinical autoimmunity in ANA+ healthy individuals. We comprehensively phenotyped immune profiles of African Americans and European Americans who are ANA-negative (ANA-) healthy, ANA+ healthy, or have SLE using single cell mass cytometry, next-generation RNA-sequencing, multiplex cytokine profiling, and phospho-signaling analyses. We found that, compared with both ANA- and ANA+ healthy individuals, patients with SLE of both races displayed T-cell expansion and elevated expression of type I and II interferon pathways. We discovered a unique immune signature that suggests a suppressive immune phenotype and reduced CD11C We propose that this novel immune signature identified in ANA+ healthy European Americans may protect them from T-cell expansion, heightened activation of interferon pathways, and disease transition.

Sections du résumé

BACKGROUND
Autoimmune diseases comprise a spectrum of illnesses and are on the rise worldwide. Although antinuclear antibodies (ANAs) are detected in many autoimmune diseases, up to 20% of healthy women are ANA-positive (ANA+) and most will never develop clinical symptoms. Furthermore, disease transition is higher among ANA+ African Americans compared with ANA+ European Americans.
OBJECTIVE
We sought to determine the immune features that might define and prevent transition to clinical autoimmunity in ANA+ healthy individuals.
METHODS
We comprehensively phenotyped immune profiles of African Americans and European Americans who are ANA-negative (ANA-) healthy, ANA+ healthy, or have SLE using single cell mass cytometry, next-generation RNA-sequencing, multiplex cytokine profiling, and phospho-signaling analyses.
RESULTS
We found that, compared with both ANA- and ANA+ healthy individuals, patients with SLE of both races displayed T-cell expansion and elevated expression of type I and II interferon pathways. We discovered a unique immune signature that suggests a suppressive immune phenotype and reduced CD11C
CONCLUSIONS
We propose that this novel immune signature identified in ANA+ healthy European Americans may protect them from T-cell expansion, heightened activation of interferon pathways, and disease transition.

Identifiants

DOI: 10.1016/j.jaci.2020.04.047 PMID: 32446964 PMC: PMC7680268
pubmed: 32446964
pii: S0091-6749(20)30675-8
doi: 10.1016/j.jaci.2020.04.047
pmc: PMC7680268
mid: NIHMS1596685
pii:
doi:

Substances chimiques

Antibodies, Antinuclear 0

Types de publication

Clinical Trial Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1419-1433

Subventions

Organisme : NIGMS NIH HHS
ID : U54 GM104938
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI082714
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI082719
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144292
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR073750
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI101934
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL104391
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007633
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR072401
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL098634
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026735
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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Auteurs

Samantha Slight-Webb (S)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla.

Miles Smith (M)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla.

Aleksandra Bylinska (A)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla.

Susan Macwana (S)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla.

Carla Guthridge (C)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla.

Rufei Lu (R)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Okla.

Joan T Merrill (JT)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla.

Eliza Chakravarty (E)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla.

Cristina Arriens (C)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla; Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Okla; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Okla.

Melissa E Munroe (ME)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla.

Holden T Maecker (HT)

Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, Calif.

Paul J Utz (PJ)

Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, Calif.

Joel M Guthridge (JM)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Okla.

Judith A James (JA)

Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Okla; Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Okla; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Okla. Electronic address: Judith-James@omrf.org.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Autoantibody-positive healthy individuals with...
questionsmedicales.fr › Personnes › Nord-Américains › Groupes de population aux États-Unis › Populations d'origine continentale › Noir ou Africain Américain › Autoantibody-positive healthy individuals with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Autoanticorps › Anticorps antinucléaires › Autoantibody-positive healthy individuals with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Autoantibody-positive healthy individuals with...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Lupus érythémateux disséminé › Autoantibody-positive healthy individuals with...
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des lymphocytes › Autoantibody-positive healthy individuals with...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Autoantibody-positive healthy individuals with...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Autoantibody-positive healthy individuals with...
questionsmedicales.fr › Personnes › Blancs › Autoantibody-positive healthy individuals with...