Distinct plasma immune signatures in ME/CFS are present early in the course of illness

Hornig, Mady; Montoya, José G.; Klimas, Nancy G.; Levine, Susan; Felsenstein, Donna; Bateman, Lucinda; Peterson, Daniel L.; Gottschalk, Claudius; Schultz, Andrew F.; Che, Xiaoyu; Eddy, M L; Komaroff, Anthony L.; Lipkin, W. Ian

doi:10.1126/sciadv.1400121

Cited by 198 publications

(209 citation statements)

References 70 publications

(78 reference statements)

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“…However, this correction was not possible with the current dataset. Findings in this study provide further evidence that ME/CFS likely involves a systemic inflammatory process (17). These findings also support biological plausibility for the propensity of these patients to experience several major and ongoing clinical manifestations, offer a mechanism for the disease's predilection to affect women and the increased risk for development of NHL, and support the suitability of exploring immunomodulation as a primary or adjuvant therapy (56,57).…”

Section: Discussionsupporting

confidence: 55%

“…[To examine the robustness of findings to the method of parameter estimation, in addition to GME, we also fit regression models to the pMFI data using ordinary least squares (OLS). An OLS (or closely allied) method was used in a previous report by Hornig et al (17). Findings reported here are similar for the GME and OLS regression methods and are available upon request.…”

Section: Methodsmentioning

confidence: 67%

“…Only CXCL9 and IL-1α inversely correlated with fatigue duration but lost statistical significance after correction for multiple comparisons (SI Appendix, Table S2). We also compared mean cytokine levels in cases with ≤3-y fatigue duration (n = 30) and those with >3-y fatigue duration (n = 156), as per Hornig et al (17). We did not find any cytokine to be significantly different between these two groups (SI Appendix, Table S3).…”

Section: Resultsmentioning

confidence: 94%

“…Also, many studies have found increased numbers of circulating cytotoxic CD8 + cells bearing activation antigens (8,(14)(15)(16). In addition, in a crosssectional study, Hornig et al (17) reported a distinct cytokine inflammatory signature associated with early disease.…”

mentioning

confidence: 98%

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Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Montoya

Holmes

Anderson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

290

234

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Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

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