Cerebrospinal Fluid Cytokine and Chemokine Profiles in Autoimmune Encephalitis: A Cross-sectional Study

Background Autoimmune encephalitis (AE) is a major cause of acute and subacute neuropsychiatric syndromes. Purpose While neuronal autoantibody testing aids diagnosis, results are often delayed or negative in seronegative cases. Cerebrospinal fluid (CSF) cytokine profiling may provide a rapid diagnostic adjunct. Methods In this cross-sectional study, we analysed CSF from 43 AE patients (29 seronegative, 9 N -methyl- d -aspartate receptor antibody-positive, 3 leucine-rich glioma-inactivated 1 (LGI1)-positive, and 2 with rare antibodies) and 34 controls (33 idiopathic intracranial hypertension and 1 viral encephalitis). Cytokine levels (IL-6, IL-7, IL-13, IL-21, CXCL10 and CXCL13) were quantified using a multiplex immunoassay. Results All measured cytokines were significantly elevated in AE compared with controls ( p < .001). CXCL10 and CXCL13 showed the largest differences between AE and controls, with CXCL13 particularly high in LGI1-positive cases. IL-6 correlated positively with IL-13 ( r = 0.47, p = .0013) and CXCL13 ( r = 0.41, p = .0064), while IL-7 correlated with IL-21 ( r = 0.33, p = .029). Cytokine profiles in seronegative AE were comparable to antibody-positive AE, with no statistically significant differences. Conclusions CSF cytokines—particularly CXCL10, CXCL13, IL-6 and IL-13—are consistently elevated in AE and reflect shared intrathecal immune activation across antibody-positive and seronegative cases. These findings are exploratory, and cytokines are proposed as adjunctive immunological markers rather than standalone diagnostic tools.