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WASHINGTON – An immunoglobulin produced by B cells that wasn't previously associated with multiple sclerosis now is, and appears to correlate with disease severity, researchers reported here.

In a small study, cerebrospinal fluid IgA levels significantly correlated with CSF levels of fetuin-A, an inflammatory protein previously found to associate with MS disease severity, Antara Finney-Stable, BS, a research assistant at the Tisch MS Research Center of New York, reported during a poster session at the .

"This is a very preliminary study showing that there's a relationship between CSF IgA B cell isotypes and fetuin-A," Finney-Stable told MedPage Today. "The ultimate goal is to be able to use IgA levels in CSF as a marker of disease severity."

Updated diagnostic criteria for MS have recently incorporated the presence of CSF IgG oligoclonal bands as a part of disease diagnosis, as most MS patients have abnormally high levels of intrathecal IgG production. Some recent work also suggests that CSF IgM levels may tell of disease severity, Finney-Stable said.

However, IgA has not been previously explored for its relationship to MS. So Finney-Stable and colleagues assessed its relationship to fetuin-A, which has previously been associated with inflammatory disease activity in MS. Indeed, in patients treated with natalizumab (Tysabri), CSF fetuin-A levels significantly decreased compared with pre-treatment levels, she said.

Her team looked for the presence of IgG, IgM, and IgA produced by B cells in CSF samples from 30 MS patients. They also collected serum samples to calculate indexes for IgG, IgM, and IgA to determine whether these immunoglobulins were produced intrathecally or if their presence in the central nervous system was from leakage of plasma proteins into the central nervous system, which the blood-brain barrier would ordinarily prevent.

Overall, they found that CSF fetuin-A levels positively correlated with CSF IgA levels (r=0.5755, P=0.0009), and further analyses showed that CSF fetuin-A levels also positively correlated with IgA index (r=0.4434, P=0.02).

The high CSF IgA index seen in the study indicated that IgA was being produced intrathecally, and that there was no suggestion of blood-brain barrier breakdown.

It's not clear why IgA may be being produced in the CNS, as these proteins are usually found in intestinal mucosa, Finney-Stable said.

"Their presence in the CNS doesn't make sense," she said. "We don't really know what they're doing in the CSF. We did some antigen screening assays and haven't found any reactivity of these B cell IgAs to any antigens. So it could tell us something about disease severity, but at this time we're not sure."

Interestingly, there were no correlations between fetuin-A and IgG or IgM levels or indexes, she reported.

More study is needed to fully elucidate the role of IgA in B-cell response in MS, Finney-Stable said. Her team is planning to investigate whether intrathecal IgA production diminishes after MS patients start B-cell therapy (e.g., with ocrelizumab).

"If they do, that would be a nice control, and it may suggest that IgA is linked to disease activity," she concluded.