IgA found in CSF during MS exacerbation could serve as a biomarker of neuroinflammation



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November 24, 2020

3 min of reading

Source / Disclosures

Disclosures:
Baranzini does not report any relevant financial information. Please see the study for the relevant financial information of all other authors.


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Gut microbiota-specific immunoglobulin A cells acted as a systemic mediator in MS, according to results published in Immunology of science – results that also suggest “a critical role” for mucosal B cells during active neuroinflammation.

Sergio Baranzini

Sergio Baranzini

“A previous article in Cell, in which we also participated, described an unprecedented phenomenon in which immunoglobulin A (IgA) producing cells from the gut migrated to the brain to dampen inflammation in an experimental (mouse) model of MS “, Sergio Baranzini, PhD, Distinguished Professor of Neurology I and Heidrich Friends and Family Endowed Chair in Neurology at the University of California, San Francisco, told Healio Neurology. “Here, we wanted to see if this process was also at play in humans with MS.”

Sergio Baranzini, PhD

Baranzini and colleagues used gene sequencing to calculate the taxa-specific IgA coating “impartially and completely”. Researchers analyzed fecal samples from MS patients, including individuals in remission (n = 25) or relapsing disease states (n = 11) and from healthy controls (n = 31).

The researchers observed differences in the amount of specific taxa between MS patients and controls, as previously reported, as well as differences in the absolute levels of IgA in the gut in patients in remission versus patients in relapsing disease states. However, they found no significant differences between MS disease states in terms of IgA-linked microbial taxa, so they pooled the cohort samples of relapsed and patients in remission for subsequent IgA sequencing analyzes.

The study results demonstrated significantly more operating taxonomic units in MS patients than in controls. When the researchers examined which specific taxia were preferentially coated with IgA, they found that operating taxonomic units were differently abundant in the IgA-positive and IgA-negative fractions of MS patients compared to controls. Baranzini and colleagues found that IgA binding was related to specific operating taxonomic units “which did not necessarily reflect the most abundant taxa in the samples” and that the positive IgA fraction associated with MS showed enrichment for regulatory elements and metabolic enzymes, the which suggests that IgA preferentially binds to MS-related bacteria and emphasizes “their immunostimulatory capacity”.

The researchers then examined how IgA immune responses influenced MS disease activity. They examined the levels of IgA and immunoglobulin G in the blood and cerebrospinal fluid in patients in remission of MS and in patients with relapsed MS. They observed a differential increase in IgA levels in cerebrospinal fluid during active MS, related to clinical relapses and MRI activity measured by the volume of the active lesion. In contrast, IgG levels were similarly elevated in the cerebrospinal fluid of MS patients during relapse and remission.

To build on their previous findings that the overall IgA coating in the gut decreased during MS relapses, Baranzini and colleagues examined the expression of mucosal homing markers in the brains of MS patients relative to healthy colon tissue. They observed expression in most IgA-producing cells in MS brain tissue, which indicated their intestinal origin, according to the study results. The researchers also found that the incidence of patients with gut microbiota-reactive IgA in CSF increased during relapsing MS compared to remission, as well as in patients with active neurosarcoidosis but not in patients with neurodegenerative disease or healthy controls.

“We found that IgA-producing cells leave the gut and enter the central nervous system during an exacerbation of MS,” Baranzini said. “These cells produce IgA which can be found in CSF and this could be a biomarker of neuroinflammation. This IgA recognizes specific molecules present on the surface of some gut bacteria, which reinforces the model that the gut and brain are part of a functional continuum -. The gut-brain axis “

According Baranzini, this is the first time that this process has been described in humans.

“Based on our previous work, we had the hypothesis that this might be the case, but that doesn’t make this result any less surprising,” he said. “Identifying exactly what these cells are doing in the brain will be an important step towards a full understanding of how MS establishes and perpetuates an inflammatory state in the brain.”

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