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

Autoimmune encephalitis (AE) is a major cause of acute and subacute neuropsychiatric syndromes.

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.

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.

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.

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.