A study recently published in the journal Nature Communications by an international research team revealed the discovery of a novel gene associated with a particular disease called common variable immunodeficiency disorder (CVID), which can lead to the development of RA. The study is entitled “Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells.”
CVID is a common primary immunodeficiency found in approximately 1 in every 25,000 individuals. It is characterized by defective immune B cells, low levels of serum immunoglobulins and weak antibody responses, leading to an increased susceptibility to infections, cancer and autoimmune or inflammatory manifestations. Genetic defects are thought to be linked to CVID but the exact cause of the disorder is unknown.
It is estimated that at least 25% of CVID patients develop autoimmune disorders, which are characterized by an overactive immune response of the body like in rheumatoid arthritis, where the body’s own immune system attacks the joints and other body parts, leading to chronic inflammation and pain. In the present study, researchers hypothesized that the genetic susceptibility to CVID could be linked to autoimmune disorders.
The research team performed the largest genetic study on CVID to date, comprising 778 CVID patients and 10,999 healthy controls from the United States, United Kingdom, Germany, Norway and Sweden. Researchers used the Immunochip, a custom-made chip capable of detecting 123,127 relevant genetic single-nucleotide polymorphisms (SNPs) linked to several immune-mediated diseases.
Researchers found that, as previously reported, the HLA (human leukocyte antigen) related gene region on chromosome 6p21 was associated to CVID. HLA corresponds to a group of proteins that help recognizing invading pathogens. Interestingly, an additional new risk gene for CVID, not HLA-related, was found at CLEC16A gene region on chromosome 16p13.13. The team found that inhibition of this particular gene in mice resulted in lower B cell levels, similar to what is observed in humans with CVID. Previous genetic studies have also linked CLEC16A with autoimmune disorders like rheumatoid arthritis and type 1 diabetes.
The research team concluded that the link between CVID and CLEC16A represents the first compelling evidence of non-HLA associations in this disease. “This is the first risk susceptibility gene for CVID identified by a genome-wide association study that does not code for the HLA complex,” said the study’s co-senior author Dr. Hakon Hakonarson, Director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia, in a news release. “Although this finding does not lead to immediate clinical applications, it raises new opportunities for understanding underlying causes of different immune disorders.”
“The biological mechanisms that cause disease symptoms in CVID are still unclear,” added Dr. Hakonarson, “but this study may suggest that altered function in CLEC16A and its associated proteins may represent a ‘missing link’ between immunodeficiency and autoimmunity in CVID. This may offer new opportunities for eventually designing more effective treatments.”