A National Health Research Institutes (NHRI) team has discovered a biomarker that could help in diagnosing the most common type of lupus earlier on, the institute said yesterday.
The group, comprised of researchers and physicians from the NHRI, Taichung Veterans General Hospital and Kaohsiung Medical University Hospital, identified several germline and somatic variants of the protein coding gene MAP4K3, also known as GLK, which can cause an overexpression of the gene in T cells, and is associated with a higher risk of developing systemic lupus erythematosus (SLE).
NHRI assistant research fellow Chuang Huai-chia (莊懷佳) said that SLE is a chronic, complex and systemic autoimmune disease that can damage multiple organs, with about 90 percent of cases occurring in women, but as each patient can have different symptoms, the disease is often difficult to diagnose early.
Photo: Lin Hui-chin, Taipei Times
A team, led by NHRI Immunology Research Center Distinguished Investigator Tan Tse-hua (譚澤華), began studying the cause and the precise biomarkers of SLE in 2009.
In 2011, they discovered that GLK, which can regulate immune inflammation responses, plays a key role in developing SLE.
They later found that GLK overexpression induces interleukin-17A production and autoimmune responses, but the mechanism of GLK overexpression in people with SLE remained unclear.
They teamed up with Taichung Veterans General Hospital and Kaohsiung Medical University Hospital to collect 431 genomic DNA samples from people who did not have SLE, and people with SLE and their family members, for next-generation sequencing.
Chuang said they found that more than 40 percent of the people with SLE have GLK germline and somatic variants, and some of the GLK overexpression induced by the variants, through the stabilization of GLK mRNAs or proteins, might be involved in the development of SLE.
The team is also the first to find that the novel E3 ligase makorin ring-finger protein 4 (MKRN4), a putative ubiquitin-protein E3 ligase, which was thought to be a pseudogene, can induce GLK protein degradation, and that downregulation and mutation of MKRN4 might also lead to GLK overexpression and subsequent induction of autoimmune responses, she said.
Tan said the findings suggest that if female family members of people with the specific GLK germline and somatic variants receive regular genetic testing, they are more likely to be diagnosed with SLE early and receive treatment.
He said the team has developed a screening kit, for which they are applying for a patent, and it is expected to be used clinically within two years.
Their research was published in the Annals of the Rheumatic Diseases last month.
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