Effects of Serum Autoantibodies on Astrocyte and Microglial Activation and Neuronal Function in ME/CFS

Dr. Marlen Alisch presented findings from laboratory investigations on the effects of autoantibodies derived from the blood of post-COVID ME/CFS patients as well as the patients’ blood itself on central nervous system (CNS) cells, particularly astrocytes, microglia, and neurons. The work of her team specifically explored the role of autoimmune mechanisms, particularly autoantibodies that target G protein-coupled receptors (GPCRs), which are involved in autonomic regulation and are expressed on CNS cells. In fact, previous research suggests that neuroinflammation, altered cytokine profiles, and activation of glial cells may contribute to ME/CFS symptoms such as fatigue, brain fog, pain, and cognitive impairment. To investigate these mechanisms, serum samples from a small sample of ME/CFS patients were incubated with human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, and microglia for 24 hours. Her team then assessed Immunoglobulin G (IgG) binding, cell viability, markers of neuronal damage, astrocytes and microglia activation, and calcium signaling to evaluate changes in cell-to-cell communication. They found that sera from a subgroup of patients displayed significantly increased IgG binding to neurons, while all sera from all patients demonstrated enhanced IgG binding to astrocytes compared with healthy controls. No significant differences in IgG binding or activation were observed in microglia. In neurons, the same subset of sera that exhibited increased antibody binding also induced an increase in markers of neuronal damage. Astrocytes exposed to certain patient sera also showed increased markers of activation. Calcium imaging, too, revealed enhanced astrocyte activity, suggesting an altered cell-to-cell communication. Their laboratory findings correlated with clinical symptoms present in the investigated patients. Greater neuronal damage was associated with higher fatigue scores, while astrocyte IgG binding and calcium signaling correlated with measures of physical and cognitive functioning. Autoantibodies present in the blood of ME/CFS patients may hence contribute to neuronal injury and astrocyte dysfunction.