Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, complex illness characterized by a significant reduction in the ability to perform pre-illness activities, lasting for more than six months, accompanied by profound fatigue that is not improved by rest. In addition to severe fatigue, ME/CFS is accompanied by post-exertional malaise (worsening of symptoms after exertion) and unrefreshing sleep. Symptoms may also include memory impairment, confusion, flu-like symptoms, headache, muscle or joint pain, and GI and genitourinary issues.
Due to the varied disease manifestations across patients, the underlying pathophysiology of ME/CFS is not fully understood, and there are no well-established biomarkers for diagnosis. Furthermore, it is unclear whether patients with ME/CFS are experiencing the same underlying disease mechanism. Therefore, a significant goal for the field has been to establish meaningful subtypes of ME/CFS that could improve diagnosis and treatment.
New data published in The Journal of Immunology, from Dr. Akiko Iwasaki, Sterling Professor of Immunobiology and Molecular, Cellular, and Developmental Biology at Yale University, and former AAI president, has identified two distinct immunotypes among individuals living with ME/CFS based on cerebrospinal fluid (CSF) cytokine analysis. These two subgroups showed different CSF inflammatory signatures with one group exhibiting elevated levels of matrix metalloproteinases (MMPs) and eight cytokines in the CSF.
“Most importantly, both groups had similar clinical presentations. This supports the idea that ME/CFS is heterogeneous and may comprise biologically distinct disease mechanisms driving similar symptomatology in different subsets of individuals,” shared Dr. Iwasaki.
“We hope these findings contribute to a shift in how ME/CFS is approached – moving away from psychologizing of the illness and towards mechanistic investigation, especially by acknowledging the complexity and heterogeneity of this disease,” added Dr. Iwasaki.
Between November 2021 and June 2022, 40 participants with ME/CFS were matched to 41 healthy controls by sex and age at the Bragée Clinic in Stockholm, Sweden. During enrollment, both cohorts were assessed for overall health, including clinical questionnaires, multiplexed analysis of cytokines, measurements of hormones and MMPs, antibodies against pathogens, and autoantibodies. CSF samples were collected from the ME/CFS group, allowing for comparison within this cohort. The comprehensive immune phenotyping of CSF and plasma samples revealed key clues to elucidate subgroups and dysregulated pathways that might drive disease.
“We believe our study makes a strong case for further immune phenotyping research into ME/CFS cohorts in the future,” said Dr. Iwasaki. The research group plans to validate these findings in larger cohorts and tissue-based studies. The group is also analyzing autoantibody profiles and their pathogenic potential for ME/CFS. Diving deeper into subsets of ME/CFS will aid the development of evidence-based individualized biomarkers and disease-modifying interventions that will hopefully benefit patients in the future.
This paper can be found in The Journal of Immunology (The JI), published by the American Association of Immunologists. As one of the most highly cited journals in the field of immunology, The JI is committed to describing novel findings in all areas of experimental immunology, including basic and clinical studies.
