2 Inflammatory Biomarkers Linked to Greater Disease Activity in SSc

Biomarkers also correlate with range of symptoms including skin ulcers

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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An illustration of white blood cells, immune cells that help to fight infection.

Elevations in two indices of body-wide inflammation are associated with greater disease activity in systemic sclerosis (SSc) patients, according to a recent study.

The two inflammatory markers — called the platelet-to-lymphocyte ratio (PLR) and platelet-to-hemoglobin ratio (PHR) — were also associated with skin ulcers, and musculoskeletal and pulmonary symptoms of the disease.

The findings did not appear to be influenced by use of immunosuppressive therapies.

PLR and PHR could thus be used as potential biomarkers of disease activity in SSc, although larger and longer studies are needed to “further analyze the relationship between disease severity and these ratios,” the study’s researchers wrote.

The study, “Significance of platelets to lymphocytes and platelets to haemoglobin ratios in patients with systemic sclerosis,” was published in the journal Reumatología Clínica.

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PLR and PHR emerging as potential biomarkers in other autoimmune conditions

Inflammation is a hallmark of autoimmune diseases such as SSc (also known as scleroderma). Thus, markers of inflammation in the blood are thought to be a promising way of predicting disease activity and severity.

Platelets, mainly known for their role in blood clotting, also play an important role in modulating the immune system. They are activated in SSc and are thought to contribute to inflammation, blood vessel damage, and scar tissue buildup (fibrosis) that mark the disease.

PLR and PHR have emerged as potential inflammatory biomarkers in other autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythematosus.

Respectively, they measure the relative levels of platelets to lymphocytes — a family of infection-fighting white blood cells — and hemoglobin, the protein that helps red blood cells to carry oxygen throughout the body. Generally speaking, a higher ratio of platelets in either of these indices is associated with greater inflammation.

However, few studies have investigated the potential role of PLR and PHR as biomarkers in SSc, and thus, a pair of researchers in Egypt set out to evaluate the relationship between the inflammatory indices and clinical manifestations of the disease.

The study involved 60 adults (85% women) diagnosed with SSc. The mean age was 40.8 years (range of 24 to 60).

The mean PLR was 245.07, and PHR was 32.96. The PLR level among this group was “high,” according to the researchers, and consistent with a previous report that PLR is elevated in SSc patients and others with inflammatory diseases.

Both indices were positively correlated with classic, but nonspecific, biomarkers of inflammation, namely C-reactive protein and erythrocyte sedimentation rate.

Moreover, both were positively correlated with disease activity, as assessed by the European Scleroderma Trials and Research Group Activity Index. As disease activity increased, so did PLR and PHR.

Likewise, certain clinical manifestations of SSc were associated with higher PLR and PHR. Particularly, the markers were significantly related to the presence of skin ulcerations, and pulmonary and musculoskeletal manifestations of SSc.

Mild restrictions in pulmonary function tests and ground glass opacity, a lung abnormality observed on high-resolution CT scans, were similarly linked to higher levels of the two indices.

The presence of anti-scleroderma-70 antibodies, a type of self-reactive antibody usually associated with diffuse forms of SSc, was also associated with the inflammatory markers.

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Immunosuppressant use did not appear to affect PLR and PHR indices

No significant differences in PLR and PHR were observed between groups of patients using immunosuppressive treatments and those not using them.

Based on the findings, the team identified a cut-off value of 107.8 for PLR and 23.5 for PHR, which were deemed highly sensitive and specific. In other words, values above this cutoff may be predictive of clinical SSc manifestations.

Overall, PLR and PHR “can be considered as a predictive biomarker for the assessment of disease activity in SSc,” the researchers wrote.

The team noted, however, a need “for results to be confirmed on a larger cohort of SSc patients,” as well as a longer-term follow-up to more accurately assess the “potential impact of specific immunosuppressive drugs on these indices.”