Lung disease monitoring called for in Scl-70 autoantibody-positive SSc

Patients positive for Scl-70 antibodies at more risk of major organ involvement by Steve Bryson, PhD 

People with systemic sclerosis (SSc) who test positive for Scl-70 self-reactive antibodies are at a higher risk of major organ involvement, particularly the lungs, than those with other types of autoantibodies, a study suggested.
Digestive tract involvement was associated with the presence of anti-nuclear (ANA) autoantibodies.

SSc patients with Scl-70 autoantibodies should be monitored for lung disease, regardless of whether their disease is limited to the skin or occurs in both skin and internal organs, the researchers recommended.

“Understanding these risk factors might help with earlier diagnosis and better disease management for people with SSc,” they noted in the autoantibody study, “Clinical phenotype in scleroderma patients based on autoantibodies,” which was published in Rheumatology Advances in Practice.

SSc, also called scleroderma, is an autoimmune disease that features the buildup of scar tissue in the skin and several other organs, potentially. It’s usually classified into two subtypes, based on the extent of skin symptoms. Limited cutaneous SSc (lcSSc) is indicated by skin symptoms confined to the face and arms below the elbows. Diffuse cutaneous SSc (dcSSc) involves widespread skin scarring that’s accompanied by internal organ damage.

“However, dividing SSc according to skin involvement might be too simplistic, meaning that we could overlook a wider spectrum of the disease,” the researchers wrote.

People with SSc have self-reactive autoantibodies that mistakenly target cellular components in their own tissues, including Scl-70, ANA, and anti-centromere (ACA) autoantibodies.
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While lcSSc has been associated with anti-ACA autoantibodies and dcSSc with anti-Scl-70 autoantibodies, some people with lcSSc are positive for Scl-70 autoantibodies and some with dsSSc are positive for ACA autoantibodies.

Organ involvement and systemic sclerosis antibodies
As such, “antibody specificity and disease subset might influence the disease phenotype [characteristics] and organ involvement,” wrote the researchers from Spain who analyzed the organ involvement and survival of 113 SSc patients in relation to the presence of autoantibodies over 15 years. A diagnosis of lsSSc was given in 82 cases (72.6%) and dcSSc in 31 (27.4%) cases.

Among those with lcSSc, 43 (52%) tested positive for anti-ACA autoantibodies, 16 (20%) with anti-Scl-70, and 23 (28%) with anti-ANA. In dcSSc patients, 13 (42%) had anti-Scl-70, 11 (35%) anti-ANA, and 7 (23%) anti-ACA.

In the lcSSc group, compared to ANA- and ACA-positive patients, those with anti-Scl-70 autoantibodies had a significantly shorter time to a SSc diagnosis after their first Raynaud’s phenomenon, which was marked by numb and prickly sensations in the fingers and toes in response to cold temperatures or stress.

Scl-70 lcSSc patients had significantly higher C-reactive protein (CRP) levels, an inflammatory marker, and higher rates of kidney disease and heart problems. Cancer rates were also higher in Scl-70-positive lcSSc patients than those positive for ACA and ANA.

The time from Raynaud’s phenomenon to SSc diagnosis was also shorter for Scl-70-positive dcSSc patients, who were younger at the onset of disease, and more often had cancer than ACA-dcSSc patients. Cases of dcSSc with anti-Scl-70 had higher levels of CRP and more myositis (muscle inflammation), kidney involvement, and heart problems than ACA- and ANA-positive cases.

The involvement of the digestive tract appeared to be associated with anti-ANA autoantibodies in both lcSSc and dcSSc.

The risk of interstitial lung disease (ILD), which is marked by inflammation and lung tissue scarring, was significantly higher in Scl-70 patients during the first 10 years than in patients who were ACA- and ANA-positive. The risk of ILD was 3.8 times higher in Scl-70-lcSSc than ACA-lcSSc and 1.5 times higher than ANA-lcSSc. Similar findings were seen in dcSSc cases.

Likewise, the risk of major organ involvement was higher in Scl-70 patients, followed by ANA and then ACA patients, across the 15-year follow-up. Major organ risk was 4.2 times higher in Scl-70-lcSSc than in ACA-lcSSc and 1.4 times higher than ANA-lcSSc. A risk of organ involvement was 1.2 times higher with anti-Scl-70 dcSSc than with anti-ACA, but not higher than anti-ANA.

While death by any cause occurred more often in people with dcSSc than in lcSSc patients, the presence of different autoantibody types didn’t affect survival overall, the analysis showed.

“We found that those with Scl-70 autoantibodies were most likely to develop problems with their major organs, particularly their lungs,” the researchers wrote. “This suggests that people with Scl-70 autoantibodies should be monitored carefully for lung disease.”
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Being a single center study with a relatively low number of patients in each group was a study limitation, the researchers noted.