Clinica chimica acta; international journal of clinical chemistry · 2026
Exploration of the source of AQP4 antibody: Based on paired serum and cerebrospinal fluid samples from 98 patients.
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Wu Tao, Jin Haiqiang, Hao Hongjun, Zheng Yiming, Guo Jing, Zhang Nan, Liu Ran, Wang Zhaoxia, Gao Feng
Аннотация
OBJECTIVE: To investigate the origin and intrathecal synthesis of aquaporin-4 antibody (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) by quantitatively measuring paired serum and cerebrospinal fluid (CSF) samples.
METHODS: This retrospective study included 98 NMOSD patients. Serum and CSF AQP4-IgG were detected using cell-based assay and ELISA. The characteristics and correlations of CSF/serum albumin ratio (Q_Alb), IgG index, 24-h IgG synthesis rate, and AQP4 antibody index (AI_AQP4) were analysed. Intrathecal synthesis was evaluated via Reiber diagram and clustered heatmap analyses.
RESULTS: Among the 98 NMOSD patients, 17 (17.35%) were positive only for serum AQP4-IgG, 40 (40.82%) were positive only in CSF, and 41 (41.83%) were positive in both serum and CSF. A significant positive correlation was observed between serum and CSF AQP4-IgG levels (rho = 0.606, p < 0.001). CSF AQP4-IgG, albumin, and IgG levels showed positive correlations with blood-brain barrier permeability (Q_Alb) (rho = 0.298, 0.935, and 0.773, respectively; p < 0.01), while no significant correlations were found with serum indicators. The CSF-only positive group exhibited significantly higher IgG index and 24-h IgG synthesis rates compared to the serum-only positive group (p < 0.05). Reiber diagram, and clustered heatmap analyses confirmed intrathecal synthesis of AQP4 antibodies.
CONCLUSION: AQP4 antibodies in NMOSD primarily originate peripherally and enter the CNS via a compromised blood-brain barrier, but significant intrathecal synthesis occurs in a subset of patients. CSF biomarkers more reliably reflect barrier dysfunction and localized immune activity than serum, highlighting the importance of CSF analysis for diagnosing intrathecal synthesis and guiding treatment.
METHODS: This retrospective study included 98 NMOSD patients. Serum and CSF AQP4-IgG were detected using cell-based assay and ELISA. The characteristics and correlations of CSF/serum albumin ratio (Q_Alb), IgG index, 24-h IgG synthesis rate, and AQP4 antibody index (AI_AQP4) were analysed. Intrathecal synthesis was evaluated via Reiber diagram and clustered heatmap analyses.
RESULTS: Among the 98 NMOSD patients, 17 (17.35%) were positive only for serum AQP4-IgG, 40 (40.82%) were positive only in CSF, and 41 (41.83%) were positive in both serum and CSF. A significant positive correlation was observed between serum and CSF AQP4-IgG levels (rho = 0.606, p < 0.001). CSF AQP4-IgG, albumin, and IgG levels showed positive correlations with blood-brain barrier permeability (Q_Alb) (rho = 0.298, 0.935, and 0.773, respectively; p < 0.01), while no significant correlations were found with serum indicators. The CSF-only positive group exhibited significantly higher IgG index and 24-h IgG synthesis rates compared to the serum-only positive group (p < 0.05). Reiber diagram, and clustered heatmap analyses confirmed intrathecal synthesis of AQP4 antibodies.
CONCLUSION: AQP4 antibodies in NMOSD primarily originate peripherally and enter the CNS via a compromised blood-brain barrier, but significant intrathecal synthesis occurs in a subset of patients. CSF biomarkers more reliably reflect barrier dysfunction and localized immune activity than serum, highlighting the importance of CSF analysis for diagnosing intrathecal synthesis and guiding treatment.