Anti-PPM1A antibodies may be AS biomarker, study finds

AS patients in study had lower levels of self-reactive antibodies

Katherine Poinsatte, PhD avatar

by Katherine Poinsatte, PhD |

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People with ankylosing spondylitis (AS) have significantly lower levels of self-reactive antibodies targeting protein phosphatase magnesium-dependent 1A (PPM1A) in their blood than healthy controls and people with rheumatoid arthritis, according to a pilot study.

PPM1A is a protein implicated in several bodily processes, including wound healing, inflammation, and regulation of growth factors.

The results suggest that anti-PPM1A antibodies may be a useful biomarker of active AS. “Decreased [anti-PPM1A antibody] levels in AS patients suggests a potential role … in the diagnosis of active AS,” the research team wrote.

Their study, “Anti-protein phosphatase magnesium-dependent 1A-IgM levels in patients with active ankylosing spondylitis: a potential biomarker,” was published in Advances in Rheumatology.

AS is a type of arthritis that affects the joints of the spinal cord, in which inflammation in the spaces between the bones of the spinal cord (the vertebrae) causes back pain and stiffness. AS symptoms, such as back pain, can occur with other conditions. The lack of a single specific test is one factor making AS diagnosis challenging.

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Imaging, blood tests for diagnosis

During the process of diagnosis, imaging tests such as X-rays are typically used to visualize AS-related alterations such as ankylosis (fusing of parts of the spine) and sacroiliitis (inflammation at the site where the spine connects to the pelvis). Blood tests may also be performed to measure common indicators of inflammation, but no definitive biomarker exists for AS.

Researchers in the Republic of Korea collected blood samples from 28 patients with active AS, 16 healthy controls, and 28 patients with a different form of arthritis known as rheumatoid arthritis.

Most participants with AS (89.3%) were male. The median time from diagnosis to enrollment in the study was eight months. All but one patient with AS were positive for HLA-B27, the strongest genetic risk factor for AS.

Baseline blood levels of C-reactive protein, a well-known marker of inflammation made by the liver, were significantly higher in the AS group than in participants with rheumatoid arthritis.

Blood levels of anti-PPM1A antibodies were significantly lower in participants with AS than in the two other groups. After adjusting for sex, results showed a trend toward a link between anti-PPM1A antibody levels and AS.

To determine the diagnostic value of these antibodies in AS, the scientists used a measure called area under the receiver operating characteristic curve (AUC). AUC values can range from 0.5 to 1, with higher numbers reflecting a better ability to distinguish between two groups — here, people with or without AS.

Measuring anti-PPM1A levels was 96.4% sensitive and 100% specific in distinguishing AS from health controls. When analyzing the distinction between AS and rheumatoid arthritis, sensitivity was 78.6% and specificity was 71.4%. Sensitivity refers to a test’s ability to correctly identify those with a disease, whereas specificity refers to the ability to correctly rule out those who do not have it.

Among the study’s limitations were a small number of patients and lacking laboratory data from the healthy controls, such as C-reactive protein levels. They also called for further studies to examine the relevance of anti-PPM1A antibodies to inactive AS, the researchers wrote.

“Therefore, the findings of the present study are noteworthy, in that it reported significant utility of a biomarker for diagnosis of active AS,” they wrote.