By Jose Montoya et al.
Background: Symptoms suggestive of inflammation are often observed in Chronic Fatigue Syndrome (CFS). Cytokine studies may substantiate an overactive immune system, but results have provided limited and sometimes, contradictory data.
Objectives: To determine whether a profile of circulating cytokines (out of 51) could be associated with CFS and correlate with disease severity.
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Methods: 192 CFS patients and 392 healthy controls (HC) had serum cytokines measured using a 51-multiplex array on the Luminex 200 IS system (Affymetrix; Santa Clara, CA). Median fluorescence intensity (MFI) data were pre-processed for each cytokine through sequence of averaging over duplicate wells per plate, natural-logarithm transformation, isolation/removal of plate effects, and centering/scaling. Multidimensional fatigue inventory (MFI- 20) scores were recorded. Each cytokine’s pre-processed data were regressed on CFS severity (control vs. tertiles on MFI-20) plus covariates for age, gender, race, and nonspecific binding via distribution-free generalized maximum entropy estimation. Post hoc estimates of trend (orthogonal linear and quadratic contrasts) across severity tertiles were obtained. All p-values were adjusted through an adaptive two-stage linear step-up procedure to control false discovery rate at 5% across 51 cytokines.
Results: Average age (± 1 SD) was 49.9 ± 12.7 years (cases) and 50.1 ± 12.5 years (controls). Proportion of female subjects was 76.6% (cases) and 77.3% (controls). In cases, TGF-? was elevated (p = 0.0076) and resistin was lower (p = 0.0076, with a non-linear trend p = 0.0362). Seventeen cytokines had a statistically significant upward linear trend that correlated with CFS severity: CCL11, G-CSF, CXCL1, CXCL10, GM-CSF, IFN-?, IL-4, IL-5, IL-7, IL-12p70, IL- 13, IL-17F, leptin, LIF, NGF, SCF, and TGF-?. P-values for the linear trend ranged from 0.0062 to 0.0366.
Conclusion: Out of 17 cytokines that correlated with severity, 13 (bolded) are pro-inflammatory, likely substantiating many of the symptoms experienced by patients and the immune nature of the disease.
: Jose G. Montoya, MD, Tyson H. Holmes, Jill N. Anderson, Holden T. Maecker, PhD, Yael Rosenberg-Hasson, PhD, Jarred W Younger*, PhD, Ian Valencia, MS, Jane Norris PA, Lily Chu, MD, MSHS, Cristina M. Tato, PhD, Mark M Davis, PhD. A Profile of Circulating Cytokines is Associated with Disease Severity in Chronic Fatigue Syndrome Patients (CFS). From IACFS/ME 2016 conference schedule
Stanford University School of Medicine, Stanford, California, 94305, USA
*Department of Psychology, University of Alabama at Birmingham, Birmingham, AL 35233, USA