Abstract： Objective:To analyze the relations of blood-brain barrier (BBB) integrity with clinical features and their response to immunotherapy in patients with autoimmune encephalitis (AE).Methods:One hundred and forty-seven AE patients confirmed in Department of Neurology, First Affiliated Hospital of Zhengzhou University from August 2015 to December 2021 were chosen; their clinical and laboratory data were collected retrospectively. In accordance with cerebrospinal fluid (CSF) albumin/serum albumin (QAlb) value of 7, patients were classified into normal BBB group ( n=101, QAlb value ≤7.00) and damaged BBB group ( n=46, QAlb value >7.00). Modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used to evaluate the severity on admission and 30 d after first-line immunotherapy; and good immunotherapy responsiveness was defined as CASE or mRS scores 30 d after first-line immunotherapy lower than those at admission. Differences of general data, clinical manifestations, CSF and peripheral blood biochemical results, and response to immunotherapy between the two groups were compared and analyzed. Results:The damaged BBB group had significantly higher proportions of patients with decreased consciousness level (58.7% vs. 37.6%), increased CSF protein, increased immunoglobulin G (IgG) and increased 24 h intramural IgG synthesis rate, and significantly higher fibrinogen in peripheral blood than normal BBB group ( P<0.05). On 30 th d of treatment, mRS scores of patients in damaged BBB group were significantly higher than those of patients in normal BBB group ( P<0.05), and the differences of CASE scores and mRS scores before and after treatment in damaged BBB group were significantly lower than those in normal BBB group (0.50±0.46 vs. 3.24±2.93, 0.70±0.62 vs. 1.15±1.04, P<0.05). In damaged BBB group, good immunotherapy response rate in patients receiving single immunotherapy was significantly lower than that in patients receiving two or three combinations of first-line immunotherapy ( P<0.05). Conclusion:BBB integrity is closely related to clinical characteristics and response to immunotherapy of AE; combined first-line immunotherapy is recommended for AE patients with BBB injury.