Immunomodulatory properties of human serum immunoglobulin A: anti-inflammatory and pro-inflammatory activities in human monocytes and peripheral blood mononuclear cells

Abstract

SummaryOur study investigated the immunomodulatory activities of human plasmaderived serum immunoglobulin (Ig)A. Previous findings seem contradictory indicating either pro-or anti-inflammatory activities. We used serum IgA purified from large plasma pools and studied the modulation of the release of cytokines and chemokines from resting and lipopolysaccharide ( We conclude that human serum IgA has both an anti-inflammatory and a pro-inflammatory capacity and this dual capacity might contribute to the feedback mechanisms maintaining a balance between pro-inflammatory and anti-inflammatory activities.

Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays

“…2), providing further evidence that these stimulated cells are mature DC. LPS, a strong inducer of proinflammatory cytokines and chemokines in various cell types [34,35], is shown here to selectively increase the expression of genes involved in inflammatory responses, such as IL1A (IL-1A), IL1B (IL-1B), IL6 (IL-6), CXCL1 and CXCL9 (Tab. 2).…”

A role for interleukin‐5 in promoting increased immunoglobulin M at the site of disease in leprosy

“…The IgA-induced pro-inflammatory properties include promoting the release of pro-IL-1b and FcaRI cross-linking can induce tumour necrosis factor-a and IL-6 from PBMC. 37,38 Therefore, the presence of IgA in L-lep skin lesions may also promote the acute inflammation observed in patients developing ENL from L-lep. In fact, single nucleotide polymorphisms of the FcaRI promoting inflammation have been described in patients with systemic lupus erythematosus.…”

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

“…37 We have demonstrated for the first time that monovalent targeting of FcaRI by mIgA inhibits IgG-mediated phagocytosis in human monocytes, 30 which explains the previously reported inhibitory functions of serum mIgA. [23][24][25][27][28][29] More importantly, we have been able to show that FcaRI-mediated inhibition is not mediated by conventional inhibitory motifs such as the immunoreceptor tyrosine-based inhibition motif. While c-less FcaRI recycles mIgA, thus playing an essential role in mIgA homeostasis, FcRc-associated FcaRI mediates either activating or inhibitory responses.…”

“…22 Several groups have demonstrated that in the absence of antigen, serum IgA downregulates IgG-mediated phagocytosis, chemotaxis, bactericidal activity, oxidative burst activity and cytokine release. [23][24][25][26][27][28][29] These IgA monomers may initiate FcaRImediated non-inflammatory responses against bacteria that breach the mucosal barrier. 30 Another piece of data supporting the inhibitory role of serum mIgA is the observation that selective IgA-deficient patients frequently present allergies and autoimmunity.…”