KAIST said on Monday that its joint research team identified the overexpression of mt-dsRNAs as a biomarker which can aid treatments of the rare and incurable autoimmune disease, Sjögren's syndrome.

Dr. Yoon Ji-min (left) and Professor Kim Yoo-sik of KAIST's Department of Biochemical Engineering have identified the overexpression of mt-dsRNAs as a new cause behind the rare and incurable autoimmune disease, Sjögren's syndrome.
Dr. Yoon Ji-min (left) and Professor Kim Yoo-sik of KAIST's Department of Biochemical Engineering have identified the overexpression of mt-dsRNAs as a new cause behind the rare and incurable autoimmune disease, Sjögren's syndrome.

Sjögren's syndrome invades exocrine glands such as tear glands and salivary glands. Occular and oral dryness are the most common symptoms, mainly affecting middle-aged women. However, one-third of patients suffer from various systemic symptoms such as lymphoma, arthritis, liver damage, and bronchitis, and can lead to premature death due to complications of malignant lymphoma and pulmonary fibrosis.

Despite the severity of the disease, the diagnosis of Sjögren's syndrome is only possible after the exocrine gland tissue damage has already progressed considerably, and its diagnosis is based on symptoms with low disease specificity.

To overcome these limitations, the research team analyzed the mechanisms of disease onset and progression to establish a new immune-controlled target substance for early diagnosis and treatment of Sjögren's syndrome.

In patients with Sjögren's syndrome, overactivation of innate immune response proteins that recognize double helix RNA (dsRNA) and antiviral interferon reactions were observed.

RNA, which exists naturally in cells, can also form dsRNA to control innate immune responses. The typical intracellular organ that produces intracellular dsRNA is mitochondria, and these mt-dsRNAs are also recognized by innate immune response proteins, which can induce interferon reactions.

The diagram shows how induced mitochondrial dsRNA from those affected with Sjögren's syndrome cause certain disease characteristics.
The diagram shows how induced mitochondrial dsRNA from those affected with Sjögren's syndrome cause certain disease characteristics.

Upon analyzing the leakage and saliva of patients with Sjögren's syndrome, the researchers confirmed the overexpression of mt-dsRNA in patient's primary cells and damaged salivary glands in Sjögren's syndrome mice models.

They also created a three-dimensional spheroid culture system of salivary gland cell lines to simulate a more accurate disease environment and found that mt-dsRNA expression increases in stress situations where immune activity is induced. However, when mt-dsRNA was suppressed, the immune activity decreased and some of the disease characteristics were restored.

Additionally, they confirmed that acetylcholine, an M3R receptor agonist, inhibits immune activity through mt-dsRNA regulation, and autoantibodies extracted from patients with Sjögren's syndrome inhibit acetylcholine, causing excessive immune activity.

Professor Kim Yoo-sik who led the study said, "By controlling immune overactivation through mt-dsRNA regulation, a new pathological marker called mt-dsRNA can be used for diagnostic and treatment strategies in Sjögren's syndrome and also other autoimmune diseases.”

The study was published in the international journal Molecular Therapy – Nuclear Acids.

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