Mood symptoms and chronic fatigue syndrome due to relapsing remitting multiple sclerosis are associated with immune activation and aberrations in the erythron.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune and neuroinflammatory disease of the central nervous system characterized by peripheral activation of immune-inflammatory pathways which culminate in neurotoxicity causing demyelination of central neurons. Nonetheless, the pathophysiology of relapsing-remitting MS (RRMS)-related chronic fatigue, depression, anxiety, cognitive impairments, and autonomic disturbances is not well understood. The current study aims to delineate whether the remitted phase of RRMS is accompanied by activated immune-inflammatory pathways and if the latter, coupled with erythron variables, explain the chronic fatigue and mood symptoms due to RRMS. We recruited 63 MS patients, 55 in the remitted phase of RRMS and 8 with secondary progressive MS, and 30 healthy controls and assessed erythron variables and used a bio-plex assay to measure 27 serum cytokines. The results indicate a significant part of the MS patients (46%) displayed activation of the immune-inflammatory response (IRS) and compensatory immune response (CIRS) systems, T helper (Th)1 and Th-17 cytokine profiles. Remitted RRMS patients showed increased chronic fatigue, depression, anxiety, physiosomatic, autonomic, and insomnia scores, which could partly be explained by M1 macrophage, Th1, Th-17, growth factor, and CIRS activation, as well as aberrations in the erythron including lowered hematocrit and hemoglobin levels. In conclusion, around 50% of remitted RRMS patients show activation of immune-inflammatory pathways in association with mood and chronic-fatigue-like symptoms. IRS and CIRS activation as well as the aberrations in the erythron are new drug targets to treat chronic fatigue and affective symptoms due to MS.

In severe first episode major depressive disorder, psychosomatic, chronic fatigue syndrome, and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity.

“…Furthermore, FF symptoms belong to the same latent construct which loads highly on affective and physiosomatic symptoms. The aforementioned interconnected relationships among FF symptoms and the phenome of depression were previously identi ed in the context of MDD 7 , acute COVID-19 infection 48 , RRMS 45 , Long COVID 49 , schizophrenia 50 , and end-stage renal disease 51 .…”

“…Furthermore, various medical and neuro-psychiatric disorders exhibit a latent construct encompassing symptoms of depression, anxiety, and physiosomatic manifestations. This phenomenon can be observed in conditions such as acute COVID-19 infection 43 , Long COVID 44 , relapsing-remitting multiple sclerosis (RRMS) 45 , schizophrenia 46 , and epilepsy 47 . Furthermore, FF symptoms belong to the same latent construct which loads highly on affective and physiosomatic symptoms.…”