Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Monocyte activation is a feature of Common Variable Immunodeficiency irrespective of plasma LPS levels

Abstract

Common Variable Immunodeficiency Disorders (CVID), the most frequent cause of symptomatic primary immunodeficiency, are defined by impaired antibody production. Notwithstanding, T-cell activation and granulomatous manifestations represent main causes of CVID morbidity even in patients under immunoglobulin G (IgG) replacement therapy. Additionally, gut pathology is a frequent feature of CVID. Here, we investigated monocyte imbalances and their possible relationship with increased microbial translocation in CVID patients. Monocyte subsets were defined according to CD14 and CD16 expression levels and evaluated in terms of HLA-DR, CD86 and PD-L1 expression by flow cytometry, in parallel with the quantification of plasma Lipopolysaccharide (LPS), and serum levels of soluble CD14 (sCD14), LPS-binding protein (LBP), and anti-LPS antibodies. CVID patients (n=31) featured significantly increased levels of serum sCD14 and an expansion of CD14brightCD16+ monocytes in direct correlation with T-cell and B-cell activation, the latter illustrated by the frequency of CD21lowCD38low subset. Such alterations were not observed in patients lacking B cells due to Congenital Agammaglobulinemia (n=4). Moreover, we found no significant increase in circulating LPS or LBP levels in CVID patients, together with a relative preservation of serum anti-LPS antibodies, in agreement with their presence in commercial IgG preparations. In conclusion, CVID was associated with monocyte imbalances that directly correlated with T-cell activation markers and with B-cell imbalances, without an association with plasma LPS levels. The heightened monocyte activated state observed in CVID may represent an important target for complementary therapeutic strategies.