Can chronic exposure to multiple mycotoxins dysregulate immune signaling and promote persistent antibody-producing B-cell activation?

Chronic exposure to mycotoxins can affect immune pathways, but the combined claim of sustained immune dysregulation with persistent antibody-producing B-cell activation remains biologically plausible rather than established in humans.

Immune-signaling effects

• Human biomarker studies of aflatoxin exposure, measured by serum aflatoxin–albumin adducts reflecting exposure over weeks to approximately two months, have associated higher exposure with lower activated T- and B-cell populations and fewer perforin/granzyme-expressing CD8 cells. These findings are consistent with altered immune regulation, although cross-sectional associations are susceptible to effects of infection, nutrition, liver disease, diet, and socioeconomic factors.
• Ochratoxin A, which persists in blood through strong albumin binding, has induced inflammatory signaling in experimental nasal epithelial cells, including increased IL-6 and IL-8. Its chronic human immunologic consequences are not established.
• In pigs, a deoxynivalenol (DON) plus fumonisin B1 mixture synergistically suppressed mitogen-stimulated lymphocyte proliferation, showing that mixtures may produce immunotoxic outcomes beyond effects of individual toxins.

B-cell and antibody-related mechanisms

• DON exposure in mice increased Peyer’s-patch IgA-bearing cells and IgA-producing activity, compatible with enhanced mucosal B-cell differentiation into IgA-secreting plasma cells. Prolonged exposure has also been linked to increased serum IgA, IgA immune complexes, and mesangial IgA deposition.
• Proposed mechanisms include IL-6–dependent helper-T-cell signaling and polyclonal B-cell activation rather than antigen-specific antibody responses. However, DON can also inhibit immunoglobulin production in purified B cells, emphasizing that dose, tissue, and immune context determine direction of effect.

Clinical interpretation

• Mixture effects are heterogeneous: immune suppression and altered cytokine or antibody responses can coexist, rather than consistently producing persistent antibody excess. Human aflatoxin observations have instead associated exposure with lower salivary secretory IgA and lower B-cell percentages.
• Bottom line: Multiple mycotoxins can plausibly perturb immune signaling and modulate B-cell–plasma-cell responses, but persistent antibody-producing B-cell activation from chronic real-world mixtures has not been demonstrated in humans.