Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome

Abstract

BackgroundChronic fatigue syndrome (CFS) is considered as a neuroimmunological disease but the etiology and pathophysiology is poorly understood. Patients suffer from sustained exhaustion, cognitive impairment and an increased sensitivity to pain and sensory stimuli. A subset of patients has frequent respiratory tract infections (RRTI). Dysregulation of the sympathetic nervous system and an association with genetic variations in the catechol-O-methyltransferase (COMT) and glucocorticoid receptor genes influencing sympathetic and glucocorticoid metabolism were reported in CFS. Here, we analyzed the prevalence of SNPs of COMT and glucocorticoid receptor-associated genes in CFS patients and correlated them to immunoglobulin levels and susceptibility to RRTI.MethodsWe analyzed blood cells of 74 CFS patients and 76 healthy controls for polymorphisms in COMT, FKBP5 and CRHR1 by allelic discrimination PCR. Serum immunoglobulins were determined by immunoturbidimetric technique, cortisol levels by ECLIA.ResultsContrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1. In patients with the Met/Met variant of COMT rs4680 we observed enhanced cortisol levels providing evidence for its functional relevance. Both enhanced IgE and diminished IgG3 levels and an increased susceptibility to RRTI were observed in CFS patients with the Met/Met variant. Such an association was not observed in 68 non-CFS patients with RRTI.ConclusionOur results indicate a relationship of COMT polymorphism rs4680 with immune dysregulation in CFS providing a potential link for the association between stress and infection susceptibility in CFS.

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

“…IgG3 and mannose binding lectin deficiency were more common among ME/CFS patients than in controls ( 102 , 103 ). IgG subclass deficiency is more frequent in ME/CFS than in controls ( 104 , 105 ).…”

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome

“…Selection of new variables was a hypothesis-driven process based on the observation that total immunoglobulins are altered in COVID-19 patients experiencing long-term symptoms (Fig. 2 ), and previous studies connecting low total IgG3 levels to chronic fatigue syndrome and increased susceptibility to infection 18 , 45 . As some variables such as “age” represent risk factors for severe COVID-19 disease, a risk factor for PACS itself 38 , we further explored the influence of COVID-19 disease severity as well as associated risk factors (Table 2 , Supplementary Table 2 , and Supplementary Fig.…”

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review

“…As a focus of this review is to exhibit the impact of dysregulation of the neuro-immuno-endocrine relationships, we aimed at summarizing several findings reporting genetic polymorphisms in key neuroimmunoendocrine-related genes that might be involved in the ME/CFS condition. There are plenty of studies that have analyzed the gene expression in the peripheral blood of patients with ME/CFS, and have proposed candidates genes related to the risk of developing the disease [154,155,156,157,158,159,160]. Unfortunately, many of these studies did not confirm their finding with PCR, making some of the proposed results unreliable [161,162].…”