In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes.
OBJECTIVE
Depression is accompanied by activation of immuno-inflammatory and oxidative and nitrosative stress (IO&NS) pathways, and increased IgM/IgA responses to lipopolysaccharide (LPS) of gram-negative commensal bacteria. The latter suggests that bacterial translocation has caused IgM/IgA responses directed against LPS. Bacterial translocation may drive IO&NS responses.


METHODS
To examine the associations between IgM/IgA responses to LPS and IO&NS measurements, including plasma/serum interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin, lysozyme, oxidized LDL (oxLDL) antibodies, peroxides, and IgM (auto)immune responses against malondialdehyde (MDA), azelaic acid, phophatidyl inositol (Pi), NO-tryptophan and NO-tyrosine in depressed patients and controls.


RESULTS
We found significant positive associations between IgM/IgA responses to LPS and oxLDL antibodies, IgM responses against MDA, azelaic acid, Pi, NO-tryptophan, and NO-tyrosine. The IgA responses to LPS were correlated with lysozyme. There were no significant positive correlations between the IgM/IgA responses to LPS and IL-1 and neopterin.


CONCLUSIONS
The findings show that in depression there is an association between increased bacterial translocation and lysozyme production, an antibacterial compound, O&NS processes, and autoimmune responses directed against O&NS generated neoantigenic determinants. It is suggested that bacterial translocation may drive IO&NS pathways in depression and thus play a role in its pathophysiology.
Maes Clinics @ Tria, Bangkok, Thailand. dr.michaelmaes@hotmail.com
M
M
Maes
M
M
Kubera
J-C
JC
Leunis
M
M
Berk
M
M
Geffard
E
E
Bosmans
D000328:Adult; D015551:Autoimmunity / Q000276:immunology* / Q000502:physiology; D018988:Bacterial Translocation / Q000276:immunology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D007375:Interleukin-1 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D009113:Muramidase / Q000097:blood; D019798:Neopterin / Q000097:blood; D009420:Nervous System / Q000276:immunology* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000939:Epitopes; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019798:Neopterin; D009113:Muramidase