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

Immunoglobulin A cells specific for the intestinal flora acted as systemic mediators in MS. Scientific immunochemistry — Findings that also suggest a “important role” for mucosal B cells during active neuroinflammation.

Sergio Balangini

“Previous treatise cellIn an (mouse) model of MS in which we participated, we explained the unprecedented phenomenon that immunoglobulin A (IgA) -producing cells move from the intestine to the brain and suppress inflammation. ” Sergio Balangini,doctorate, A prominent professor of Neurology I at the University of California, San Francisco, and a chairman who donated neurology to Heydrich’s friends and family, told Healtho Neurology. “Here I wanted to test if this process works in people with multiple sclerosis.”

Baranzini et al. Used gene sequencing to calculate taxon-specific IgA coatings “in an unbiased and comprehensive manner.”Researchers analyzed fecal specimens from patients with multiple sclerosis, including individuals in remission (n = 25) or Recurrent medical condition From (n = 11), and healthy controls (n = 31).

Researchers have previously reported differences in the amount of specific classifications between MS patients and controls, as well as differences in absolute intestinal IgA levels in patients in remission compared to patients with recurrent medical conditions. Was observed. However, they found no significant differences between MS pathologies for the IgA-binding microbial taxa, so they pooled samples from a cohort of relapsed and remitted patients for subsequent IgA sequence analysis.

The study results showed that patients with MS had a significantly higher number of surgical classification units compared to controls. When researchers investigated which specific taxis was preferentially coated with IgA, the IgA-positive and IgA-negative fractions of MS patients had an exceptionally rich number of operational classification units compared to controls. I found out. Baranzini et al. Found that IgA binding correlated with specific operational taxa that “do not necessarily reflect the most abundant taxa in the sample,” and that MS-related IgA-positive fractions showed enrichment of regulatory elements and metabolic enzymes. I found. It preferentially binds to MS-related bacteria and emphasizes “their immunostimulatory ability”.

Next, researchers investigated how the IgA immune response affects the disease activity of MS. They examined IgA and immunoglobulin G levels in blood and cerebrospinal fluid in patients with MS remission and those with recurrent MS. They observed different elevations of CSF IgA levels during active MS. This correlated with clinical recurrence and MRI activity as measured by the volume of active lesions. In contrast, IgG levels were similarly elevated in CSF in MS patients during recurrence and remission.

Based on the previous finding that the overall IgA coating of the intestine was reduced during the recurrence of MS, Baranzini et al. Examined the expression of mucosal homing markers in the brains of MS patients compared to healthy colon tissue. .. They observed expression in most IgA-producing cells of MS brain tissue. This indicates the origin of the intestine, according to research results. Researchers also found that the incidence of gut flora-responsive IgA in CSF was increased during recurrent MS compared to remission and was increased in patients with active neurosarcoidosis, but with neurodegenerative disease or We found that there was no increase in healthy control patients.

“We found IgA-producing cells leaving the intestine and entering the CNS during the deterioration of MS,” Baranzini said. “These cells produce the IgA found in CSF, which may be a biomarker of neuroinflammation. This IgA recognizes specific molecules present on the surface of certain gut flora. This enhances the following models: Intestines and brain It is a functional continuum, part of the cerebrointestinal axis. “

According to Balangini, this is the first time this process has been explained in humans.

“Based on our previous research, we hypothesized that this might be the case, but this doesn’t make this finding so surprising,” he said. “Identifying exactly what these cells are doing in the brain is an important step in fully understanding how MS establishes and perpetuates the inflammatory state in the brain. Become.”