Immune Genes May Be Biomarkers of SSc Diagnosis, Therapy Response

Activity of two genes, particularly, change with experimental treatments

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Various immune-related genes are not equally as active in people with systemic sclerosis (SSc) as they are in healthy individuals, and they may be candidate biomarkers for diagnosis, a study suggests.

Researchers also found that two of these genes, called TNFSF13B and TYROBP, may tell how well people with SSc, also known as scleroderma, respond to experimental treatment with cyclophosphamide or a stem cell transplant.

These are among genes that may serve as “diagnostic indicators and potential biomarkers for SSc,” the researchers wrote.

The study, “Identification and validation of key immune-related genes with promising diagnostic and predictive value in systemic sclerosis,” was published in the journal Life Sciences.

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557 gene seen as more or less active with systemic sclerosis

Scleroderma occurs when the immune system becomes overly active and out of control. This leads cells in the skin’s connective tissue to produce too much collagen, causing thickening and scarring (fibrosis). Other organs may become scarred, too.

What exactly turns the immune system overactive is not clear, but genes are thought to be involved and certain sets may be used as molecular barcodes to tell disease subtypes apart.

To know which genes may be candidate biomarkers to help in diagnosis and find out how well treatment is working, the researchers drew on a dataset of skin biopsy samples from 48 people with SSc and 33 healthy individuals as a control group.

They looked at messenger RNA, a type of molecule that carries a gene’s information from DNA to where proteins are produced. They wanted to determine which genes had their activity either boosted or damped down.

Activity levels differed for a total of 557 genes, being either higher (482 genes) or lower (75 genes) in scleroderma patients than controls.

With the help of databases and other research resources, the team identified 169 immune-related genes that had their activity either boosted (158 genes) or damped down (11 genes).

Some of these immune-related genes were involved in the production of proteins that help in the immune response and the movement of white blood cells, also called leukocytes. Others were involved in communication within cells and their surroundings.

When the researchers crossed this information with two other datasets, they found that the genes NGFR, TNFSF13B, FCER1G, GIMAP5, TYROBP, and CSF1R may be of value in diagnosing scleroderma. This potential diagnostic ability in the skin was greater than that seen in blood.

“Therefore, NGFR, TNFSF13B, TYROBP, CSF1R, FCER1G and GIMAP5 in skin tissues are more suitable as auxiliary diagnostic indicators for SSc,” the researchers wrote.

Because blood samples are more accessible than those of the skin when trying to find out how well a treatment is working, the researchers compared the blood of 62 untreated SSc patients with samples from 35 patients after 26 months of therapy. Treatment given with either cyclophosphamide, a chemotherapy sometimes used to treat scleroderma with lung involvement, or a stem cell transplant.

The activity of both TNFSF13B and TYROBP was damped down after treatment, suggesting that these two genes “could become promising biomarkers for predicting therapeutic effects in SSc,” the researchers wrote.

“However, more samples from clinical SSc patients are still needed to validate our findings,” they added.