Cerebrospinal Fluid IgA Levels Correlate with Disease Activity in Patients with Multiple Sclerosis; A Novel Finding

Objective: To better understand the cerebrospinal fluid [CSF] antibody repertoire and its correlation with disease in patients with MS. Background: In a continuing study, we performed single cell analysis on CSF B-cells and identified their immunoglobulin isotypes. We recently discovered a clinically definite MS patient, where more than half of the 67 B-cells analyzed were of the same IgA isotype B-cell clone. Due to this unusual finding, we decided to quantify IgA antibody levels in the CSF of MS patients, as well as levels of IgG and IgM. We also detected levels of fetuin- A and osteopontin, markers that have been previously linked to inflammatory disease activity. Design/Methods: CSF and serum samples from 30 MS patients were analyzed by ELISA for IgG, IgM, and IgA levels. Albumin levels were also determined and the Ig Indices calculated. CSF was further analyzed by ELISA for fetuin-A, and osteopontin. Significant correlations were determined by a non-parametric Spearman test using the statistical program GraphPad Prism. Results: CSF fetuin-A levels significantly correlated with CSF IgAs (r = 0.5755, p = 0.0009). Further analyses showed that CSF fetuin-A levels also significantly correlated with the IgA index (r = 0.4434, p = 0.0205). No correlations were found with IgG indexes, IgM indexes, and osteopontin. Conclusions: We have identified a subset of MS patients with high CSF IgA levels that has not been reported in previous literature. Further investigation is required to elucidate the role of IgAs in the B-cell response for MS. In addition, high CSF IgA levels were an indicator of intrathecal IgA production and do not support a presence of a blood brain barrier breakdown. Unlike IgG and IgM, IgA antibodies appear to correlate with disease activity, because of the positive correlation to CSF fetuin-A levels. Future studies should be performed to determine if intrathecal IgA production decreases post-treatment in MS. Study Supported by: Emerald Foundation

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