Neuro endocrinology lettersJun 27, 2008

Immune response targeting damaged proteins linked to nitrosative stress in chronic fatigue syndrome and major depression

Updated Apr 3, 2026

Abstract

Serum IgM levels directed against nitro-BSA were significantly greater in patients with chronic fatigue syndrome (CFS) and major depression (MDD) compared to normal controls.

Increased serum IgM levels against nitro-BSA were found in 13 patients with CFS, 14 subjects with partial CFS, and 16 patients with MDD.
CFS patients exhibited significantly higher IgM levels than those with partial CFS and MDD.
Positive correlations were observed between serum IgM levels against nitro-BSA and symptoms of aches, pain, and muscular tension as measured by the FibroFatigue scale.
A strong positive correlation was noted between serum IgM titers against nitro-BSA and markers of increased gut permeability.
The findings suggest that CFS and MDD may be associated with increased gut permeability and nitrosative stress, leading to an IgM-mediated immune response.

Simplified

BACKGROUND: It has been shown that chronic fatigue syndrome (CFS) and major depression (MDD) are accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS and MDD are accompanied by an IgM-mediated immune response directed against nitro-serum bovine albumin (BSA), which is a neoepitope of BSA formed by damage caused by nitrosative stress.

AIMS: Toward this end, we examined serum IgM antibodies to nitro-BSA in 13 patients with CFS, 14 subjects with partial CFS, 16 patients with MDD and 11 normal controls.

RESULTS: We found that the prevalence and mean values for the serum IgM levels directed against nitro-BSA were significantly greater in patients with partial CFS, CFS and MDD than in normal controls, and significantly greater in CFS than in those with partial CFS and MDD. We found significant and positive correlations between serum IgM levels directed against nitro-BSA and symptoms of the FibroFatigue scale, i.e. aches and pain and muscular tension. There was also a strong positive correlation between serum IgM titers directed against nitro-BSA and an index of increased gut permeability ("leaky gut"), i.e. serum IgM and IgA directed against LPS of different gram-negative enterobacteria.

DISCUSSION: The abovementioned results indicate that both CFS and MDD are accompanied by a) an increased gut permeability which has allowed an exaggerated passage of BSA through a compromised epithelial barrier; b) increased nitrosative stress which has induced damage to BSA; and c) an IgM-mediated immune response which is directed against the nitro-BSA neoepitopes. Nitrosative stress is one of the factors underpinning the comorbidity and clinical overlap between CFS and MDD.

Immune response targeting damaged proteins linked to nitrosative stress in chronic fatigue syndrome and major depression

Abstract

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