NAT10 may be biomarker for diagnosis, disease progression of AS
Gene is less active in blood cells of people with condition
A gene called NAT10 is less active in blood cells from people with new-onset ankylosing spondylitis (AS) than in those from healthy people, suggesting it may serve as a diagnostic biomarker, a study suggests.
When combined with higher levels of immune cells called neutrophils, a less active NAT10 gene was linked to more severe disease, suggesting it also may be a biomarker for disease progression.
AS occurs when the sacroiliac joint at the base of the spine become inflamed. This can cause a range of symptoms, from pain and stiffness in the lower back and hips to tenderness and fatigue.
An early diagnosis can be difficult as the disease may not have progressed to a point where damage is visible on an X-ray. Misdiagnoses also can occur because the disease’s symptoms vary among people and a number of other diseases manifest like AS.
Researchers in China checked how active the NAT10 gene is in people with AS versus healthy people or those with other diseases and whether it could offer a specific test for the disease. “The early correct diagnosis of AS is important in order to decrease disease burden through early intervention to reduce disability experienced by many patients,” they wrote.
NAT10 gene and AS diagnosis, progression
The NAT10 gene codes for a protein that controls gene expression, the process by which the information encoded in a gene is turned into a protein. This process is crucial for the proper functioning of cells. The role of the protein in AS is unclear though.
The study included 56 people who’d been recently diagnosed with AS, 52 healthy (control) people, 20 people with rheumatoid arthritis, and 16 with systemic lupus erythematosus. Both rheumatoid arthritis and lupus share symptoms with AS.
The genetic information in a gene is copied into a molecule called messenger RNA (mRNA), which translates the information into a protein. To check how active the NAT10 gene was, the researchers measured its mRNA levels.
The mean levels of NAT10 mRNA in peripheral blood mononuclear cells — that is, circulating blood cells with a single, round nucleus — were significantly lower in those with new-onset AS than healthy people regardless of age and sex.
The lower the levels of NAT10 mRNA, the higher the AS Disease Activity Score (ASDAS-CRP), which stratifies disease severity using clinical data and the levels of C-reactive protein, a biomarker of inflammation. A higher score indicates more severe disease.
There also was an inverse relationship between NAT10 mRNA levels and the Bath AS Disease Activity Index (BASDAI) score, a measure of disease activity where a score of 4 or greater indicates active disease.
The cutoff NAT10 mRNA for distinguishing people with AS from controls was 0.521, with a sensitivity of 48.2% and a specificity of 90.4%. Sensitivity refers to how well NAT10 levels can diagnose AS in people who actually have the disease. Specificity is the proportion of people in whom an AS diagnosis is correctly ruled out.
To improve sensitivity, the researchers combined NAT10 mRNA levels with neutrophil percentage (N%), as they found that N% was significantly increased in new-onset AS patients relative to controls.
That combination performed better at diagnosing AS, with a sensitivity of 84.6% and a specificity of 76.9%. Adding HLA-B27, a risk factor for AS, was even better — the sensitivity was 92.9% and the specificity 100%.
When combined with the neutrophil percentage, a less active NAT10 was able to tell people with AS from those with rheumatoid arthritis or lupus. It was also linked to more severe disease, suggesting it could be a biomarker for disease progression.
“The role of NAT10 in AS may provide insights into the pathogenesis [disease mechanisms] of AS,” the researchers wrote. However, “the precise mechanisms underlying the functions of NAT10 in AS still need to [be investigated].”