Increased autoimmune responses against auto-epitopes modified by oxidative and nitrosative damage in depression: implications for the pathways to chronic depression and neuroprogression.
OBJECTIVE
There is evidence that major depression is characterized by oxidative and nitrosative stress (O&NS). The aim of this study is to examine IgM-mediated autoimmune responses against a variety of modified neo-epitopes formed by O&NS damage to self-epitopes in chronic depression.


METHODS
Serum IgM antibodies directed against conjugated oleic and azelaic acid, malondialdehyde (MDA), phosphatidyl inositol (Pi), and conjugated nitric-oxide (NO) adducts, i.e., NO-tryptophan, NO-tyrosine, NO-arginine, and NO-cysteinyl, were determined in 33 healthy controls and 74 depressed patients subdivided into 28 patients with chronic (duration >2 year) and 46 without chronic depression.


RESULTS
Serum IgM levels against all neoepitopes were significantly higher in depressed patients than in healthy controls. Moreover, the IgM levels were significantly higher, except Pi, in chronically depressed patients than in non-chronically depressed patients.


CONCLUSIONS
Depression is characterized by IgM-related autoimmune responses directed against neo-epitopes that are normally hidden from the immune system but that became immunogenic secondary to damage by O&NS. The results show that the generation of neoantigenic determinants that lead to (auto)immune responses is strongly associated with chronic depression.


CONCLUSIONS
The damage caused by O&NS to auto-epitopes and the consequent formation of O&NS modified neoantigenic determinants may increase the risk to develop depression and in particular chronic depression through transition to autoimmune reactions. This has implications for understanding the immuno-inflammatory and oxidative-autoimmune pathways that lead to chronic depression and neuroprogression in that illness.
Maes Clinics @ TRIA, Bangkok, Thailand. dr.michaelmaes@hotmail.com
Michael
M
Maes
Marta
M
Kubera
Ivana
I
Mihaylova
Michel
M
Geffard
Piotr
P
Galecki
Jean-Clude
JC
Leunis
Michael
M
Berk
D000328:Adult; D015551:Autoimmunity / Q000276:immunology; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005227:Fatty Acids / Q000276:immunology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000276:immunology; D018384:Oxidative Stress / Q000276:immunology
D000939:Epitopes; D005227:Fatty Acids; D007075:Immunoglobulin M; D009569:Nitric Oxide