Professors Lee Sang-won (left) and Lee Sang-kyu

Researchers at Severance Hospital have successfully found a treatment method for lupus nephritis that controls the transcription factor of inflammatory T cells.

Although clinical studies of biological agents targeting autoimmune cells or substances are underway, no new therapeutic agents have shown superior efficacy in lupus nephritis, according to Severance. Steroid-based injections of anti-cancer agents and oral immunosuppressant are the existing treatment methods.

However, Severance noted these conventional therapies have the potential to cause side effects by unconditionally reducing the number and function of inflammatory T cells. Inflammatory T cells are essential for healthy immune function.

Researchers at Yonsei University found that nucleus-transducible form of Transcription Modulation Domain (TMD) of Tbet (ntTbet-TMD) reduces kidney inflammation as well as proteinuria and damage to kidney tissue in animal studies.

Professors Lee Sang-won from Yonsei University Severance Hospital, Department of Rheumatic Internal Medicine, and Lee Sang-kyu from Yonsei University, Department of Biotechnology led the study.

Researchers said ntTbet-TMD is significant in that it opens the possibility of a “biofriendly” therapeutic agent for treating lupus nephritis by selectively controlling the part involved in autoimmune inflammation.

"We have identified the potential for developing new therapies for patients who do not benefit from existing standard of care treatments or cannot get sufficient treatment due to side effects,” said Professor Lee Sang-won.

The research team had developed ntTbet-TMD in 2012 and worked with Good T Cells to develop the drug and prove its efficacy.

According to findings, ntTbet-TMD controls the function of inflammatory T-cell transcription factors, which play an essential role in the development and worsening of lupus nephritis, and inhibit the production of inflammatory substances.

The animal studies showed that ntTbet-TMD has significant effects on reducing the amount of proteinuria, inflammation, and damage to kidney tissue.

Findings showed administrating a high dose of the substance led to a 73.8 percent decrease in proteinuria compared to the untreated group while the low dose group saw a 58.1 percent decrease.

Kidney tissues of those in the untreated group showed apparent damage in the form of an expanded glomerulus, cell proliferation, and inflammatory cell infiltration. There were no side effects in the ntTbet-TMD group.

Lupus is an autoimmune disease that manifests various symptoms by an immune response that attacks and recognizes its body as an external substance. Lupus nephritis, which causes inflammation by invading the kidney, can lead to chronic kidney failure or dialysis within five years for around 10 to 20 percent of patients with a poor prognosis even after treatment.

The study was published in the May issue of the journal Kidney International.

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