Researchers Explore Prediction of Scleroderma Renal Crisis With Anti-RNAP III

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Scleroderma Renal Crisis

Scleroderma Renal CrisisScientists from the Department of Dermatology at the Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan have confirmed that antibodies to a specific enzyme — RNA polymerase III — are associated with scleroderma renal crisis (SRC). RNA polymerase III’s normal function is to convert (transcribe) DNA into RNA. Antibodies to RNA polymerase III are called anti-RNAP III, for short. The article appeared in the journal Arthritis and Rheumatology.

SRC can occur in 5-10% of people with systemic sclerosis (SSc) — an autoimmune disorder that damages normal tissue. SSc causes accumulation of collagen and widespread damage to the blood vessels, including thickening of the blood vessel walls. SRC is a serious complication of SSc, and is characterized by hypertension, sudden kidney (renal) failure, headaches, fevers, tiredness, high blood pressure in the retina of the eye, brain disease and the collection of watery fluid in the lungs. Patients with a form of SSc called diffuse systemic sclerosis (dcSSc) are at higher risk for SRC than those with limited systemic sclerosis (lcSSc). Angiotensin converting enzyme inhibitors are the conventional treatment for SRC, and kidney transplant may also be required in some cases.

The researchers, led by Yasuhito Hamaguchi of the Department of Dermatology, Kanazawa University Graduate School of Medical Science, studied 583 adult Japanese patients with SSc, and screened them for the presence of anti-RNAP III, using standard methods for detecting antibodies, known as Enzyme-Linked-Immunosorbent-Assay (ELISA) and immunoprecipitation.

Thirty-seven patients (6%) had measured some kind of anti-RNAP III. When the investigators looked for specific types of anti-RNAP III, they found that 19 patients had a form called anti-RNAP I/III, 17 had anti-RNAP I/II/III, and 1 had anti-RNAP III. SRC was measured in 17 (2.9%) of the 583 patients, and anti-RNAP III-positive SSc patients (9/37, 24%) were more commonly observed that those without anti-RNAP III (8/546, 1%). This was a highly statistically significant effect.

Based on these results, the scientists concluded that “as reported previously, anti-RNAP III is associated with SRC . . . anti-RNAP III might be associated with developing SRC in SSc patients . . .

Measuring the anti-RNAP III protein in people with SRC could provide a predictive biomarker that might aid in treatment could possibly even facilitate prevention. Right now, about two-thirds of patients with SRC will need a kidney transplant. Only half of these patients will eventually recover enough to no longer require dialysis. Improved prevention of SRC could result in more positive outcomes for people with SSc. Fortunately, ELISA kits to detect anti-RNAP III are readily available commercially, and thus could potentially be used in the clinic.