Increased antiviral response in circulating lymphocytes from hypogammaglobulinemia patients.

B cells Hypogammaglobulinemia antiviral response common variable immunodeficiency lymphocytes monocytes rhinovirus

Journal

Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028

Informations de publication

Date de publication:
12 2020
Historique:
received: 02 12 2019
revised: 21 04 2020
accepted: 29 04 2020
pubmed: 14 6 2020
medline: 15 5 2021
entrez: 14 6 2020
Statut: ppublish

Résumé

B cells play a crucial role during rhinovirus (RV) infections by production of virus-neutralizing antibodies. A main feature of common variable immunodeficiency (CVID) is hypogammaglobulinemia (HG). HG patients have severely reduced levels of antibody-producing B cells and suffer from prolonged virus infections. Here, we addressed whether antiviral response of peripheral blood lymphocytes differs between HG patients and healthy individuals during natural RV infection. Using fluorescence-activated cell sorting, B-cell subsets were analyzed. Simultaneously, CD19 + B cells, CD14 + monocytes, and CD3 + T cells were sorted from frozen peripheral blood mononuclear cells from 11 RV-infected hypogammaglobulinemia patients, 7 RV-infected control subjects, and 14 noninfected control subjects. Real-time PCR was used to study expression of antiviral genes. A pan-RV PCR was used to detect RV genome in all samples. In HG patients, total B-cell numbers, as well as IgA + and IgG + switched memory B cells, were reduced while naïve B cells and T cells were increased. STAT1 expression was increased in HG patients compared to controls in all lymphocyte subsets analyzed. The expression of antiviral genes IFITM1 and MX1 correlated with STAT1 expression in B cells and monocytes. RV RNA was found in 88.9% of monocytes from infected HG patients, 85.7% of monocytes from infected controls, and 7.1% of monocytes from uninfected controls. We demonstrate an increased antiviral response in B cells and monocytes in HG patients and their correlation with STAT1 expression. Monocytes of infected HG patients and infected non-HG controls carry RV RNA.

Sections du résumé

BACKGROUND
B cells play a crucial role during rhinovirus (RV) infections by production of virus-neutralizing antibodies. A main feature of common variable immunodeficiency (CVID) is hypogammaglobulinemia (HG). HG patients have severely reduced levels of antibody-producing B cells and suffer from prolonged virus infections. Here, we addressed whether antiviral response of peripheral blood lymphocytes differs between HG patients and healthy individuals during natural RV infection.
METHODS
Using fluorescence-activated cell sorting, B-cell subsets were analyzed. Simultaneously, CD19 + B cells, CD14 + monocytes, and CD3 + T cells were sorted from frozen peripheral blood mononuclear cells from 11 RV-infected hypogammaglobulinemia patients, 7 RV-infected control subjects, and 14 noninfected control subjects. Real-time PCR was used to study expression of antiviral genes. A pan-RV PCR was used to detect RV genome in all samples.
RESULTS
In HG patients, total B-cell numbers, as well as IgA + and IgG + switched memory B cells, were reduced while naïve B cells and T cells were increased. STAT1 expression was increased in HG patients compared to controls in all lymphocyte subsets analyzed. The expression of antiviral genes IFITM1 and MX1 correlated with STAT1 expression in B cells and monocytes. RV RNA was found in 88.9% of monocytes from infected HG patients, 85.7% of monocytes from infected controls, and 7.1% of monocytes from uninfected controls.
CONCLUSIONS
We demonstrate an increased antiviral response in B cells and monocytes in HG patients and their correlation with STAT1 expression. Monocytes of infected HG patients and infected non-HG controls carry RV RNA.

Identifiants

pubmed: 32533713
doi: 10.1111/all.14445
doi:

Substances chimiques

Antiviral Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3147-3158

Informations de copyright

© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Références

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Auteurs

Oliver F Wirz (OF)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Öykü Üzülmez (Ö)

Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.

Kirstin Jansen (K)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Willem van de Veen (W)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.

Auli Lammela (A)

Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Leena Kainulainen (L)

Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Tytti Vuorinen (T)

Department of Clinical Virology, Turku University Hospital, Turku, Finland.
Department of Virology, University of Turku, Turku, Finland.

Heimo Breiteneder (H)

Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.

Cezmi A Akdis (CA)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.

Tuomas Jartti (T)

Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.

Mübeccel Akdis (M)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

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