A new commentary concerning genetic variability in multiple sclerosis patients highlights a new marker of disease severity. Local IgG (antibody) synthesis is found in over 90% of multiple sclerosis patients, and there is a genetic basis for this hallmark of disease.
“A new genome-wide association study (GWAS) by An Goris and colleagues has evaluated the contribution of genetic factors to variations in antibody levels in the cerebro spinal fluid (CSF) of patients with multiple sclerosis (MS),” wrote Dr. Jose C. Álvarez-Cermeño and Dr. Luisa M. Villar, authors of the commentary entitled “Genetic Variability Affects CNS IgG Production in MS,” which was published in Nature Reviews Neurology. “The researchers identified genetic variants that are associated with the likelihood of showing CSF oligo–clonal bands or a high IgG index—signs of intrathecal antibody production.”
In other words, patients with multiple sclerosis produce antibodies within the sheath surrounding the spinal cord. The fact that this occurs is a sign of ongoing stimulation of the immune system that leads to more advanced stages of disease.
The study under review, “Genetic Variants are Major Determinants of CSF Antibody Levels in Multiple Sclerosis,” was written by a large collaboration led by Dr. An Goris and Dr. Hanne F. Harbo and published in the journal Brain. In this study, the authors were testing the hypothesis that there is a genetic influence on antibody production in multiple sclerosis patients that may correlate to disease aggressiveness.
To test this hypothesis, the research team conducted a GWAS that covered nine countries and nearly 7,000 patients. The team was looking at traits in the antibody levels of the CSF of multiple sclerosis patients. Specifically, they were identifying the presence or absence of oligoclonal bands, IgG index levels, and replication.
Their results agreed with previous studies that identified oligoclonal band status of certain genes, but they also found novel associations between genes and IgG status. Additionally, the team found that, “Both traits are associated with clinical features of disease such as female gender, age at onset and severity.”
Dr. Goris noted, “This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants.” Since the study was well-supported, it suggests that identifying antibody levels in the CSF of multiple sclerosis patients may indicate the aggressiveness of disease.