Modulatory Effects of Antibody Replacement Therapy to Innate and Adaptive Immune Cells

Abstract

Intravenous immunoglobulin administered at replacement dosages modulates innate and adaptive immune cells in primary antibody deficiencies (PAD) in a different manner to what observed when high dosages are used or when their effect is analyzed by in vitro experimental conditions. The effects seem to be beneficial on innate cells in that dendritic cells maturate, pro-inflammatory monocytes decrease, and neutrophil function is preserved. The effects are less clear on adaptive immune cells. IVIg induced a transient increase of Treg and a long-term increase of CD4 cells. More complex and less understood is the interplay of IVIg with defective B cells of PAD patients. The paucity of data underlies the need of more studies on patients with PAD before drawing conclusions on the in vivo mechanisms of action of IVIg based on in vitro investigations.

Multisystem Inflammatory Syndrome in Children (MIS-C), a Post-viral Myocarditis and Systemic Vasculitis—A Critical Review of Its Pathogenesis and Treatment

“…It provides passive immunity to many infectious agents including common coronaviruses that may share epitope specificity with SARS-CoV-2, as well as bacterial agents and endotoxins (including SEB). Furthermore, IVIG serves as an immunomodulator of both innate and adaptive immunity by multiple mechanisms (140).…”

Clinical management of patients with primary immunodeficiencies during the COVID-19 pandemic

“…Few papers described the beneficial effect of high doses immunoglobulins administered in COVID-19 patients on improving symptoms, fever, and lymphopenia, although the selected patients were not affected by IEI [17]. It has been widely demonstrated that IVIG exert immunomodulatory effects on many inflammatory cells such as monocytes [18] and may also contain antibodies directed to other coronaviruses potentially cross-reactive with COVID-19 [19]. Due to the widespread and long-term circulation of human coronaviruses, and the pooling of plasma from thousands of donors for every lot, immunoglobulins might contain levels of antihuman seasonal coronaviruses antibodies.…”

SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: everybody does their best

“…The adaptive immune response develops slowly and needs two weeks to generate the most specific and effective defensive tools. However, the vast majority of PAD patients infected with SARS-CoV-2 did not show signs of hyper-activation of the innate immunity [3][4][5], an effect possibly due to the immunomodulatory effects on innate immune cells due to the regular use of polyvalent immunoglobulins [30], and a poor adaptive immunity. This pattern of immune responses resembles what we have already shown in asymptomatic immunocompetent subjects [36], and further demonstrated that a balanced cytokine production resulting from a functional but not hyper-reactive innate immunity and a poor adaptive immunity are the conditions associated with an early benign COVID-19 course.…”