Analysis of the Relationship between Immune Dysfunction and Symptom Severity in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Sharni Lee Hardcastle

doi:10.4172/2155-9899.1000190

Abstract

Objective: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a disabling illness, characterised by persistent, debilitating fatigue and a multitude of symptoms. Immunological alterations are prominent in CFS/ME cases, however little is known about the relationship between CFS/ME severity and the extent of immunological dysfunction. The purpose of this study was to assess innate and adaptive immune cell phenotypes and function of two groups of CFS/ME patients, bedridden (severe) and mobile (moderate). Methods: CFS/ME participants were defined using the Centres for Disease Prevention and Control (1994 CDC) Criteria for CFS/ME. Participants were grouped into healthy controls (n=22, age=40.14 ± 2.38), moderate/ mobile (n=23; age=42.52 ± 2.63) and severe/bedridden (n=18; age=39.56 ± 1.51) CFS/ME patients. Flow cytometric protocols were used to examine neutrophil, monocyte, dendritic cells (DCs), iNKT, Treg, B, γδ and CD8+ T cell phenotypes, NK cytotoxic activity and receptors. Results: The present data found that CFS/ME patients demonstrated significant decreases in NK cytotoxic activity, transitional and regulatory B cells, γδ1T cells, KIR2DL1/DS1, CD94+ and KIR2DL2/L3. Significant increases in CD56-CD16+NKs, CD56dimCD16- and CD56brightCD16-/dim NKs, DCs, iNKT phenotypes, memory and naive B cells were also shown in CFS/ME participants. Severe CFS/ME patients demonstrated increased CD14-CD16+ DCs, memory and naive B cells, total iNKT, iNKT cell and NK phenotypes compared to moderate CFS/ME patients. Conclusion: This study is the first to determine alterations in NK, iNKT, B, DC and γδ T cell phenotypes in both moderate and severe CFS/ME patients. Immunological alterations are present in innate and adaptive immune cells and sometimes, immune deregulation appears worse in CFS/ME patients with more severe symptoms. It may be appropriate for CFS/ME patient severity subgroups to be distinguished in both clinical and research settings to extricate further immunological pathologies that may not have been previously reported.

Highlights

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a severe physically and cognitively incapacitating illness diagnosed by symptom-specific criteria [1,2,3]
Age data is represented as Mean ± SEM in control (n=22), moderate CFS/ME (n=23) and severe CFS/ME (n=18). *signifies p
The severe CFS/ME subgroup of patients experienced further immunological function in some instances. These findings suggest that immune perturbations may be further persistent in CFS/ME patients who experience more severe CFS/ME symptoms and may potentially dictate illness severity, as occurs in other diseases, such as rheumatoid arthritis (RA) [67,68,69]

Summary

Introduction

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a severe physically and cognitively incapacitating illness diagnosed by symptom-specific criteria [1,2,3]. CFS/ME presents as a multifactorial illness that varies greatly in the nature of onset and severity of symptom presentation [1,2,4,5]. A key characteristic is debilitating fatigue that lasts for a period of 6 or more months that has a critical effect on a patient’s daily activities are critically affected [1,2,3,6].The severity of symptoms can vary greatly in CFS/ME. For example patients with moderate symptoms are able to maintain some normal daily activities with slight reduced mobility while those severely affected by CFS/ ME experience high levels of daily fatigue and are typically housebound [7]. We have previously been the only research group to have examined Natural Killer (NK) cell function, phenotype and receptors in housebound severe patients in comparison to a healthy control group [13]. Housebound severe patients had significantly reduced NK cell cytotoxic activity when compared with the moderately affected patients and there was an increase in the Killer Immunoglobulin-like Receptor (KIRs) KIR3DL1 in the moderate patients, highlighting that differing levels of severity may have varying levels of immune perturbation [13]

Results

Discussion

Conclusion