CCP Antibodies Linked to ILD, Worse Lung Function in SSc Patients

An anti-CCP antibody test may help with early detection of ILD

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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People with systemic scleroderma (SSc) who test positive for cyclic citrullinated peptide (CCP) antibodies are more likely than those who test negative to develop interstitial lung disease (ILD) — when the lungs become scarred — and have worse lung function.

That’s according to data from a South Korean study that included people with systemic lupus erythematosus (SLE) or myositis, disorders with symptoms that sometimes overlap with scleroderma.

The study, “A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and interstitial lung disease in systemic sclerosis,” was published in Scientific Reports.

A CCP antibody test looks for anti-CCP antibodies in the blood. They are a type of autoantibody that wrongfully turns against healthy tissues in the joints.

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A positive test for anti-CCP antibodies in the blood can indicate rheumatoid arthritis, an autoimmune disease that causes pain, swelling, and stiffness in the joints. It can also indicate the likelihood of developing symptoms outside the joints, such as ILD.

Scleroderma occurs when autoantibodies attack the skin’s connective tissue, the body’s framework. In scleroderma, producing a protein called collagen in excessive amounts makes the skin harden and scar. In SSc, a type of scleroderma, the attack includes other organs. If the joints are affected, patients may have arthritis-like symptoms.

It’s not known if anti-CCP antibodies play a role in developing SSc. What the researchers knew is that anti-CCP antibodies in the blood are linked to lung fibrosis (scarring) with SSc. They report now that “an anti-CCP antibody test may be helpful for early detection of ILD in SSc patients.”

The study included 260 people with a diagnosis of SSc, 936 people with SLE, and 156 with polymyositis/dermatomyositis (PM/DM), two types of myositis, who received care at a Seoul hospital between January 2005 and May 2021.

A higher proportion of people with SSc (16.2%) tested positive for anti-CCP antibody compared to those with SLE (9.2%) or PM/DM (11.5%).

Prevalence of anti-CCP antibodies

Of the 42 people with SSc who tested positive for anti-antibodies, 37 (88.1%) also tested positive for rheumatoid factor (RF) antibodies. An RF test is often used to help diagnose rheumatoid arthritis and other autoimmune diseases.

ILD occurred about twice as often in those with SSc who tested positive for either anti-CCP antibodies (64.3%) or RF antibodies (61.2%) than in those who were negative (32.5%). Similar observations were made with SLE, but not with PM/DM.

Some also had a diagnosis of rheumatoid arthritis. The disease was more common among those who tested positive for anti-CCP antibodies than among those who tested positive for RF antibodies in SSc (42.9% vs. 16.4%) and in SLE (57% vs. 25.2%).

When the researchers looked at the characteristics of anti-CCP antibody-positive people with SSc, they found they had joint pain and erosion (bone loss) more frequently that those without anti-CCF antibodies. They also tested positive more frequently for anti-Scl-70 antibodies, a type of autoantibody that’s a marker of the diffuse type of scleroderma.

In contrast, abnormalities in the small blood vessels (called capillaries) under the fingernails — a sign of Raynaud’s phenomenon — were not as common as in those who tested negative for CCP antibodies.

Chest high-resolution CT scans revealed that usual interstitial pneumonia (UIP) — a pattern of ILD that’s the hallmark of idiopathic pulmonary fibrosis, a form of ILD — was seen significantly more commonly in those who tested positive for anti-CCP antibodies than in the other SSc patients (55.6% vs. 31.1%).

“Anti-CCP antibody may be associated with a higher incidence of ILD in SSc,” the researchers wrote.

ILD can make breathing difficult. DLCO — short for diffusing capacity for carbon monoxide, a measure of the ability of gas to transfer from the small airways of the lungs to the red blood cells — was significantly lower in those who tested positive for anti-CCP antibodies than in the other SSc patients (57.2% vs. 67.8%). This means their lung function was worse.

CCP antibodies in the blood, as well as RF or Scl-70 antibodies, were linked to developing ILD in people with SSc.

“Research is needed to evaluate treatment response according to anti-CCP antibody positivity in SSc,” the researchers wrote, noting it’s “important to identify serologic [blood] markers to guide treatment strategies.”