Meeting News

Temporal link exists between cancer, scleroderma onset

Fredrick M. Wigley

DESTIN, Fla. — There is a close temporal link between cancer and the onset of scleroderma in patients with anti-RNA polymerase III, as well as Anti-RNPC-3 antibodies, with compelling evidence suggesting that cancer-induced autoimmunity is triggered by this process, according to Fredrick M. Wigley, MD, director of the Johns Hopkins Scleroderma Center.

“Remember that antibodies to RNA polymerase III are associated with rapid diffuse skin disease, as well as an increased risk for renal crisis, joint contractions, heart disease and cancer,” Wigley told attendees here.

“Some time ago, I was noticing that when patients came in with rapid skin changes, they often had a diagnosis of scleroderma soon after they presented with their disease,” he added. “Because of that, we had one of our fellows review all of our patients, and what she discovered is that, if you look at the interval of the onset of scleroderma and cancer, when the cancer was diagnosed, and you look at the serology, there was a striking, tight association in those individuals that had RNA polymerase III antibodies and those who were negative for anti-topoisomerase and other associated known antibodies, while there was no such association with cancer in the other serological groups.”

 
There is a close temporal link between cancer and the onset of scleroderma in patients with anti-RNA polymerase III, as well as Anti-RNPC-3 antibodies, according to Wigley.
Source: Adobe

According to Wigley, there was a 4- to 5-fold increase in cancer within 2 years of scleroderma onset in patients with RNA polymerase III antibodies.

“This has been confirmed in many other cohorts around the country,” he said.

Wigley reviewed findings from two studies he co-authored, one published in 2014 in Science and the other in 2018 in Annals of the Rheumatic Diseases, examining these links. In the first study, Wigley and colleagues examined cancers from patients with scleroderma and found genetic alterations to the RNA Polymerase III Subunit A gene in six of eight patients with anti-RNA polymerase III antibodies but not in the eight patients without them.

In addition, an analysis of peripheral blood lymphocytes and serum suggested that RNA Polymerase III Subunit A mutations triggered cellular immunity and cross-reactive humoral immune responses, according to the researchers.

In the 2018 study, Wigley and colleagues analyzed 2,383 patients with scleroderma, of whom 205 had cancer, at the Johns Hopkins Scleroderma Center. They found that, within 3 years of scleroderma onset, cancer risk was increased in patients with RNA polymerase III autoantibodies. In addition, among patients with RNA polymerase III autoantibodies, specific cancer risks varied by scleroderma subtype. For example, patients with diffuse scleroderma demonstrated an increased risk for breast cancer, and those with limited scleroderma had an increased risk for lung cancer, according to Wigley.

Meanwhile, patients who were positive for anticentromere antibodies demonstrated a lower risk for cancer during follow-up.

“So, if you are confronted with a patient who has anti-RNA polymerase III, the question is ‘How much do I do to look for cancer in that patient?’ because about 20% will develop a cancer,” Wigley said. “We do the conventional, traditional, complete cancer workout for these patients, and we are now in the midst of research looking at whether or not looking for tumor markers in the blood that may be circulating, and looking at PET scans and so forth, would be helpful.” – by Jason Laday

Reference:

Wigley FM. What’s new in scleroderma. Presented at: Congress of Clinical Rheumatology; May 2-5, 2019; Destin, Fla.

Disclosures : Wigley reports research grants from Boehringer Ingelheim, Corbus, CSL Behring, Cumberland, Cytori and GlaxoSmithKline.

Fredrick M. Wigley

DESTIN, Fla. — There is a close temporal link between cancer and the onset of scleroderma in patients with anti-RNA polymerase III, as well as Anti-RNPC-3 antibodies, with compelling evidence suggesting that cancer-induced autoimmunity is triggered by this process, according to Fredrick M. Wigley, MD, director of the Johns Hopkins Scleroderma Center.

“Remember that antibodies to RNA polymerase III are associated with rapid diffuse skin disease, as well as an increased risk for renal crisis, joint contractions, heart disease and cancer,” Wigley told attendees here.

“Some time ago, I was noticing that when patients came in with rapid skin changes, they often had a diagnosis of scleroderma soon after they presented with their disease,” he added. “Because of that, we had one of our fellows review all of our patients, and what she discovered is that, if you look at the interval of the onset of scleroderma and cancer, when the cancer was diagnosed, and you look at the serology, there was a striking, tight association in those individuals that had RNA polymerase III antibodies and those who were negative for anti-topoisomerase and other associated known antibodies, while there was no such association with cancer in the other serological groups.”

 
There is a close temporal link between cancer and the onset of scleroderma in patients with anti-RNA polymerase III, as well as Anti-RNPC-3 antibodies, according to Wigley.
Source: Adobe

According to Wigley, there was a 4- to 5-fold increase in cancer within 2 years of scleroderma onset in patients with RNA polymerase III antibodies.

“This has been confirmed in many other cohorts around the country,” he said.

Wigley reviewed findings from two studies he co-authored, one published in 2014 in Science and the other in 2018 in Annals of the Rheumatic Diseases, examining these links. In the first study, Wigley and colleagues examined cancers from patients with scleroderma and found genetic alterations to the RNA Polymerase III Subunit A gene in six of eight patients with anti-RNA polymerase III antibodies but not in the eight patients without them.

In addition, an analysis of peripheral blood lymphocytes and serum suggested that RNA Polymerase III Subunit A mutations triggered cellular immunity and cross-reactive humoral immune responses, according to the researchers.

In the 2018 study, Wigley and colleagues analyzed 2,383 patients with scleroderma, of whom 205 had cancer, at the Johns Hopkins Scleroderma Center. They found that, within 3 years of scleroderma onset, cancer risk was increased in patients with RNA polymerase III autoantibodies. In addition, among patients with RNA polymerase III autoantibodies, specific cancer risks varied by scleroderma subtype. For example, patients with diffuse scleroderma demonstrated an increased risk for breast cancer, and those with limited scleroderma had an increased risk for lung cancer, according to Wigley.

Meanwhile, patients who were positive for anticentromere antibodies demonstrated a lower risk for cancer during follow-up.

“So, if you are confronted with a patient who has anti-RNA polymerase III, the question is ‘How much do I do to look for cancer in that patient?’ because about 20% will develop a cancer,” Wigley said. “We do the conventional, traditional, complete cancer workout for these patients, and we are now in the midst of research looking at whether or not looking for tumor markers in the blood that may be circulating, and looking at PET scans and so forth, would be helpful.” – by Jason Laday

Reference:

Wigley FM. What’s new in scleroderma. Presented at: Congress of Clinical Rheumatology; May 2-5, 2019; Destin, Fla.

Disclosures : Wigley reports research grants from Boehringer Ingelheim, Corbus, CSL Behring, Cumberland, Cytori and GlaxoSmithKline.

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