Header

UZH-Logo

Maintenance Infos

Increased antiviral response in circulating lymphocytes from hypogammaglobulinemia patients


Wirz, Oliver F; Üzülmez, Öykü; Jansen, Kirstin; van de Veen, Willem; Lammela, Auli; Kainulainen, Leena; Vuorinen, Tytti; Breiteneder, Heimo; Akdis, Cezmi A; Jartti, Tuomas; Akdis, Mübeccel (2020). Increased antiviral response in circulating lymphocytes from hypogammaglobulinemia patients. Allergy, 75(12):3147-3158.

Abstract

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.

Abstract

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.

Statistics

Citations

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Uncontrolled Keywords:Immunology, Immunology and Allergy
Language:English
Date:1 December 2020
Deposited On:11 Jan 2021 10:58
Last Modified:26 Jan 2021 20:35
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0105-4538
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/all.14445
PubMed ID:32533713

Download

Full text not available from this repository.
View at publisher

Get full-text in a library