Intravenous immunoglobulin replacement induces an in vivo reduction of inflammatory monocytes and retains the monocyte ability to respond to bacterial stimulation in patients with common variable immunodeficiencies

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

“…IVIg infusions could exert an anti-inflammatory function, even if administrated at replacement dosages, acting on monocytes as we recently showed in monocyte from CVID [23]. Interestingly, in line with our previous observation, XLA patients showed an increased percentage of intermediate monocyte, possibly caused by their inflammatory condition.…”

“…These time points were chosen based on our previous observations [23, 38], taking into consideration that the highest increase of several cytokines plasma concentration occurs within one hour after IVIg infusion [39]. Total peripheral blood monocytes and neutrophils count were determined from blood cell counts and white blood cell differentials.…”

“…Monocytes subpopulations were phenotypically selected by gating on CD14 + HLA-DR + monocytes and then classified according to their expression of CD14 and CD16 into classical (CD14 ++ CD16 - ), intermediate (CD14 ++ CD16 + ) and non classical monocytes (CD14 + CD16 ++ ). An isotype control (IgG 1 , BD) with the same fluorochrome of CD16 antibody was run in parallel in order to set the boundary between classical and intermediate monocytes [23]. The surface expression of CD181, CD11b, CD11c and Siglec 9 receptors was evaluated on monocytes samples from erythrocytes-lysed whole blood, performing a staining at 4°C for 30 min with combinations of fluorochrome-labeled antibodies.…”

“…The standard therapy in XLA is the administration of human polyvalent immunoglobulins G (IgG) [19, 20] that beside their antibody replacement activity have been shown to modulate innate immune cells [21, 22]. We have previously shown that in patients affected by a different PAD entity, the Common Variable Immune Disorders (CVID) [23], the IgG administration reduced the overexpression of CD11b and of sialic acid-binding immunoglobulin-like lectin receptor (Siglec 9) on monocytes and the frequency of peripheral pro-inflammatory monocytes. The expansion of pro-inflammatory monocytes has been observed also in other systemic inflammatory diseases [24, 25] together with an overexpression of CD11c, a receptor involved in adherence and phagocytosis [26, 27].…”

“…Siglec 9 is a member of transmembrane sialic acid-binding proteins CD33-related [31, 32] with a postulated inhibitory activity on the immune response through host and bacterial sialoglycans recognition [33, 34]. The simultaneous expression of CD11b and Siglec 9 might play a pivotal role in monocytes activity [23]. CD11c is an integrin molecule, which is a member of αXβ2 receptor that overlap the properties of αMβ2 integrin involved in adherence and phagocytosis of complement coated particles [26, 27].…”