CTSS Protein May Cause Lupus in Females

CTSS Protein May Cause Lupus in Females

New research pinpoints a protein as a potential cause of lupus in females. The study shows that reduced expression of the protein Blimp-1 is associated with an increase in the protein CTSS (cathepsin S), which causes the immune system to attack female lupus patients’ healthy cells. Although further research is needed, these result suggest the potential for new treatment options for female lupus patients.

One of the main components of the immune system is the ability of immune cells to present foreign particles called antigens to T-cells, which then work to eliminate potential pathogens from our bodies. CTSS  is one of the proteins that regulates this presentation. Prior studies have shown that the expression of CTSS plays a role in maintaining balance of immune system components.

The gene PRDM1 codes for the protein Blimp-1 and has been found to be a risk factor in patients with lupus in genome-wide association studies. Therefore, researchers at Feinstein Institute for Medical Research used mice that were deficient in Blimp-1 to study how this particular protein may affect the immune system. Blimp-1 helps to cause or inhibits expression of genes and has previously been found to be a risk factor in patients with lupus in genome-wide association studies

The research, titled “Increased cathepsin S in Prdm1−/− dendritic cells alters the TFH cell repertoire and contributes to lupus,” was published in the journal Nature.

Results from this study show that Blimp-1 regulates CTSS expression in a type of immune cell called dendritic cells. When there is a decreased expression of Blimp-1, as is the case in some lupus patients, it causes an increase in the expression of CTSS.

The researchers found that an increase in expression of CTSS changed the types of particles that were presented to T-cells for clearance from the body. This caused the immune system to attack normal, healthy cells. Interestingly, this phenomenon was only present in females, not males.

“A healthy immune system is able to identify organisms that are not normally in the body and activate cells like T-Cells to attack them,” said Dr. Diamond, MD, Professor at Feinstein Institute for Medical Research.  “In the case of patients with an autoimmune disease like lupus, the immune system has started to identify healthy cells as something to target.  Our study found that a low level of or no Blimp-1 protein in a particular cell type led to an increase in the protein CTSS, which caused the immune system to identify healthy cells as something to attack – particularly in females.”

Researchers then inhibited CTSS in the mice, which led to a decrease in the development of the lupus phenotype that previously characterized these Blimp-1 deficient mice. This indicates that this could potentially be a treatment for female patients with lupus. However, further researcher needs to be conducted in order confirm that Blimp-1 is responsible for the overactive immune system in female lupus patients.

 

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