Increased antiviral response in circulating lymphocytes from hypogammaglobulinemia patients

Abstract

<p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>In HG patients, total B-cell numbers, as well as IgA + and IgG + switched memory B cells, were reduced while naive B cells and T cells were increased. <em>STAT1</em> expression was increased in HG patients compared to controls in all lymphocyte subsets analyzed. The expression of antiviral genes <em>IFITM1</em> and <em>MX1</em> correlated with <em>STAT1</em> 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.</p><p>Conclusions</p><p>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.</p>