{"id":23683,"date":"2020-01-09T21:14:25","date_gmt":"2020-01-09T21:14:25","guid":{"rendered":"https:\/\/wames.org.uk\/cms-english\/?p=23683"},"modified":"2020-01-09T21:16:02","modified_gmt":"2020-01-09T21:16:02","slug":"__trashed-66","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/__trashed-66\/","title":{"rendered":"Perturbation of effector & regulatory T cell subsets in ME\/CFS"},"content":{"rendered":"

Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis\/ Chronic Fatigue Syndrome (ME\/CFS<\/a>), by Ece Karhan, Courtney Gunter, Vida Ravanmehr, Meghan Horne, Lina Kozhaya, Stephanie Renzullo, Lindsey Placek, Joshy George, Peter N Robinson, Suzannne D Vernon, Lucinda Bateman, Derya Unutmaz in<\/span> bioRxiv<\/em> \u00a02019.12.23. 887505<\/h3>\n

 <\/p>\n

Abstract:<\/strong><\/h3>\n

\"\"<\/a>Myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) is a debilitating disorder of unknown etiology, and diagnosis of the disease is largely based on clinical symptoms. We hypothesized that immunological disruption is the major driver of this disease and analyzed a large cohort of ME\/CFS patient or control blood samples for differences in T cell<\/a> subset frequencies and functions. We found that the ratio of CD4+ to CD8+ T cells and the proportion of CD8+ effector memory T cells were increased, whereas NK cells were reduced in ME\/CFS patients younger than 50 years old compared to a healthy control group.<\/p>\n

Remarkably, major differences were observed in Th1, Th2, Th17 and mucosal-associated invariant T (MAIT) T cell<\/a> subset functions across all ages of patients compared to healthy subjects. While CCR6+ Th17 cells in ME\/CFS secreted less IL-17 compared to controls, their overall frequency was higher. Similarly, MAIT cells from patients secreted lower IFNgamma;, GranzymeA and IL-17 upon activation. Together, these findings suggest chronic stimulation of these T cell populations in ME\/CFS patients.<\/p>\n

In contrast, the frequency of regulatory T cells (Tregs<\/a>), which control excessive immune activation, was higher in ME\/CFS patients. Finally, using a machine learning algorithm called random forest<\/a>, we determined that the set of T cell parameters analyzed could identify more than 90% of the subjects in the ME\/CFS cohort as patients (93% true positive rate or sensitivity).<\/p>\n

In conclusion, these multiple and major perturbations or dysfunctions in T cell subsets in ME\/CFS patients suggest potential chronic infections or microbiome dysbiosis<\/a>.<\/p>\n

These findings also have implications for development of ME\/CFS specific immune biomarkers and reveal potential targets for novel therapeutic interventions.<\/p>\n

 <\/p>\n

Press release:<\/strong> JAX Research on Immune Profiles in ME\/CFS is now Available Online, 27 Dec 2019<\/a><\/h3>\n

…In this detailed study, we analyzed the immunological differences between ME\/CFS patients and healthy controls within a large cohort and found several major differences in T cell subset frequencies and functions between the two groups.<\/p>\n

\u2026 the ratio of two major subsets of T cells, namely the CD4+ to CD8+ T cell ratio, was increased in ME\/CFS patients compared to healthy controls.<\/p>\n

\u2026 There was also a major difference seen between healthy controls and ME\/CFS patients in the Th17 cell subset, which is involved in responding to bacteria and is also a culprit in several autoimmune and chronic inflammatory conditions… we think this suggests a chronic activation of Th17 cells in ME\/CFS which induces an ‘exhausted’ state where the cells are more dysfunctional due to their chronic stimulation.<\/p>\n

…There was also a major difference seen in the mucosal-associated invariant T (MAIT) cells in ME\/CFS patients compared to healthy controls… \u00a0It is possible that these changes in Th17 and MAIT cells are associated with differences in the composition of the microbiota of the ME\/CFS patients, and that a disruption in the microbiota causes chronic activation of these subsets and an exhausted state in ME\/CFS patients.<\/p>\n

Interestingly, we also noted that regulatory T cells (Tregs) were increased in ME\/CFS patients compared to controls. Tregs function to suppress excessive chronic immune responses, so this is consistent with our finding that there appears to be chronic activation of major T cell subsets in ME\/CFS patients.<\/p>\n

Finally and importantly, we utilized these immune profiling parameters in a machine learning classifier and were able to correctly identify ME\/CFS patients from healthy controls with high sensitivity and accuracy. As patients often wait years to receive an ME\/CFS diagnosis since there are currently no clear diagnostic tools to identify the disease, the development of an immune profile classier could aid as a biomarker to diagnose the disease.<\/p>\n","protected":false},"excerpt":{"rendered":"

Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis\/ Chronic Fatigue Syndrome (ME\/CFS), by Ece Karhan, Courtney Gunter, Vida Ravanmehr, Meghan Horne, Lina Kozhaya, Stephanie Renzullo, Lindsey Placek, Joshy George, Peter N Robinson, Suzannne D Vernon, Lucinda Bateman, … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[5505,1011,59,35,5506,927,5499,5502,5500,4981,5503,4749,5498,5501,4412,1047,5504],"class_list":["post-23683","post","type-post","status-publish","format-standard","hentry","category-news","tag-courtney-gunter","tag-dr-derya-unutmaz","tag-dr-lucinda-bateman","tag-dr-suzanne-vernon","tag-ece-karhan","tag-immune-dysfyunction","tag-joshy-george","tag-lina-kozhaya","tag-lindsey-placek","tag-mait-cells","tag-meghan-horne","tag-microbiome","tag-peter-n-robinson","tag-stephanie-renzullo","tag-t-regulatory-cells","tag-tregs","tag-vida-ravanmehr"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5qkYK-69Z","_links":{"self":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/23683","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/comments?post=23683"}],"version-history":[{"count":3,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/23683\/revisions"}],"predecessor-version":[{"id":23784,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/23683\/revisions\/23784"}],"wp:attachment":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/media?parent=23683"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/categories?post=23683"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/tags?post=23683"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}