Differential immunomodulation of T-cells by immunoglobulin replacement therapy in primary and secondary antibody deficiency

Abstract

Patients with primary or secondary antibody deficiency (PAD or SAD) are at increased risk of recurrent infections that can be alleviated by immunoglobulin replacement therapy (IRT). In addition to replenishing antibody levels, IRT has been suggested to modulate immune response in patients with antibody deficiency. Although both commonly treated with IRT, the underlying causes of PAD and SAD vary greatly, suggesting differential modulation of T-cell function that may lead to different responses to IRT. To explore this, peripheral blood mononuclear cells (PBMCs) were sampled from 17 PAD and 14 SAD patients before and 2–10 months after initiation of IRT, and analyzed for changes in T-cell phenotype and function. Proportions of CD4, CD8, Treg, or memory T-cells did not significantly change post-IRT compared to pre-IRT. However, we report distinct modulation in T-cell function between PAD and SAD patients post-IRT. Upon α-CD3/CD28 stimulation, proportion of IFN-γ+ CD4 and CD8 T-cells increased in SAD (p = 0.005) but not PAD patients post-IRT compared to baseline. Interestingly, total T-cell proliferation was reduced post-IRT in both PAD and SAD patients, although the reduction in proliferation was primarily due to reduced CD4 T-cell proliferation in PAD (p = 0.025) in contrast to CD8 T-cells in SAD (p = 0.042). In summary, even though IRT provides patients with passive humoral immunity-mediated protection in PAD and SAD, our findings suggest that IRT immunomodulation of T-cells is different in T-cell subsets depending on underlying immunodeficiency.

Clinical and immunological characterization of IgG subclass deficiency reveals that low levels of pneumococcal antibodies associate with need of immunoglobulin replacement therapy

“…Absolute numbers of B cells, NK-cells, CD4 and CD8 T cells did not differ between IgGsd patients and healthy controls and were not affected by IgRT, which is in line with a previous report of an unselected cohort of PAD [24]. Deeper analysis of B and T cells subsets in our study showed that activated (CD25 + ) B cells were lower in IgGsd and normalized during IgRT.…”

Intravenous Immunoglobulin: Mechanism of Action in Autoimmune and Inflammatory Conditions

“…1 As IVIG contains antibodies to diverse pathogens, the main goal of low-dose replacement therapy is to prevent recurrent infections in primary immunodeficient patients or in patients with recurrent infections with secondary immunoglobulin deficiencies. Several lines of evidence also suggest that low-dose IVIG therapy can exert positive effects on the cellular immune compartment, depending on underlying immunodeficiency [8][9][10][11][12] . In contrast, most autoimmune conditions require high dose therapy.…”

Using Intravenous Immunoglobulin in a Patient With Septic Shock and Multiple Comorbidities: A Review Based on a Clinical Case

“…IVIG is also widely used to treat necrotizing soft tissue infections. It is also used for various autoimmune, inflammatory neurological, skin, and immunodeficiency diseases, as well as in the case of COVID-19 and reproductive medicine [14,15,16,17]. The meta-analysis of available clinical studies on the use of IVIG in Group A streptococcal toxic shock syndrome indicates benefits in terms of patient survival after severe septic shock [18].…”