Clinical characteristics, immunological alteration and distinction of MOG-IgG-associated disorders and GFAP-IgG-associated disorders

Abstract

The classification of autoimmune encephalitis (AE) is based on the presence of different types of antibodies. Currently, the clinical manifestations and treatment regimens of patients with all types of AE exhibit similarities. However, the presence of immunological distinctions among different types of AE remains uncertain. In this study, we prospectively collected clinical data, as well as blood and cerebrospinal fluid (CSF) samples from patients diagnosed with MOG antibody-associated disease (MOGAD) or GFAP astrocytopathy (GFAP-A), in order to assess changes in inflammatory biomarkers such as immunoglobulin oligoclonal bands, cytokines in serum and CSF, as well as peripheral blood lymphocyte subtypes within different subsets. To further distinguish the immune response in patients with MOGAD and GFAP-A from that of healthy individuals, we prospectively recruited 20 hospitalized patients diagnosed with AE. Among them, 15 (75%) tested positive for MOG antibodies, 4 (20%) tested positive for GFAP antibodies, and 1 (5%) tested positive for both MOG and GFAP antibodies. These patients were then followed up for a period of 18 months. Compared to healthy controls (HC), AE patients exhibited elevated levels of MIP-1beta, SDF-1alpha, IL-12p70, IL-5, IL-1RA, IL-8 and decreased levels of IL-23, IL-31, IFN-alpha, IL-7, TNF-beta and TNF-alpha in serum. The CSF of AE patients showed increased levels of IL-1RA, IL-6 and IL-2 while decreased levels of RANTES, IL-18,IL-7,TNF-beta,TNF-alpha,RANTES,Eotaxin,and IL-9. The level of MCP-1 in the CSF of GFAP-A patients was found to be lower compared to that of MOGAD patients, while RANTES levels were higher. And the levels of IL-17A, Eotaxin, GRO-alpha, IL-8, IL-1beta, MIP-1beta were higher in the CSF of patients with epilepsy. The presence of intrathecal immune responses is also observed in patients with spinal muscular atrophy (SMA). However, no biomarker was found to be associated with disease severity in patients with AE. Among the 17 patients, recovery was observed, while 2 patients experienced persistent symptoms after an 18-month follow-up period. Additionally, within one year of onset, 8 patients had a single recurrence. Therefore, the immunological profiles of MOGAD and GFAP-A patients differ from those of normal individuals, and the alterations in cytokine levels may also exhibit a causal association with the clinical presentations, such as seizure.