Simple Blood Test May Help Predict Disease Course, Mortality in SSc

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A scientist looks at a serum sample under a microscope.

A differential blood cell count — a routine test that tells how many cells of each type there are in the blood — may be able to foretell the course of disease in patients with systemic scleroderma (SSc), according to a U.S. study.

Higher numbers in both neutrophil counts and neutrophil-to-lymphocyte ratios were found to predict more severe disease over time and worse mortality. Neutrophils and lymphocytes are two types of white blood cell that can be counted in a routine blood test. These “easily obtainable” counts could serve as biomarkers of disease progression, researchers noted.

The study, “Blood neutrophil count and neutrophil-to-lymphocyte ratio predict disease progression and mortality in two independent systemic sclerosis cohorts,” was published in the journal Arthritis Care & Research.

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People with scleroderma experience hardening and tightening of the skin. The systemic type can also affect the internal organs. When the lungs are involved, there may be scarring, and scarred lungs can make it hard to breathe.

Cells of the adaptive immune system are activated early in the course of the disease and contribute to scarring by making antibodies that mistakenly attack healthy tissues.

Recent research suggests that cells of the innate immune system, which provides a first line of protection in a non-specific way, may also be involved. One such cell type are neutrophils, which promote scarring by releasing enzymes that cut into pieces the extracellular matrix that is involved in repairing damaged tissues. Neutrophils also provide a bridge between the adaptive and innate immune systems by controlling the response of other immune cells.

The researchers knew that gene activity related to neutrophils is elevated in the blood of patients with SSc. Now, they wanted to determine whether the amount of neutrophils and lymphocytes could predict severe disease and mortality over time.

The researchers drew on data from the Genetics versus ENvironment in Scleroderma Outcomes Study (GENISOS), a study of the University of Texas Health Science Center in Houston that collects information from patients with early SSc.

When a patient entered the study, their skin thickness was tested using the modified Rodnan Skin Score (mRSS). Lung function was assessed using the predicted percentage of forced vital capacity (FVC%), a measure of how much air a patient can exhale during a forced breath. These measures were used as indicators of disease severity, with higher mRSS and lower FVC% indicating more severe disease.

Of the 377 patients with SSc who were part of GENISOS and had available blood neutrophil and lymphocyte counts, 67 (17.8%) were men and 223 (59.2%) had diffuse cutaneous SSc for a mean 2.5 years. Patients with diffuse involvement are more likely to have extensive skin scarring and internal organ damage.

Both a higher neutrophil count and a higher neutrophil-to-lymphocyte ratio were linked to diffuse involvement of the disease. Moreover, they both predicted higher mRSS and lower FVC% over time.

When the researchers looked at mortality, they found that higher levels in both measures predicted increased risk of dying at three, five, and 10 years, even after adjusting for demographic and clinical factors.

Patients who had a higher neutrophil count when they entered the study had a 47% higher chance of dying than those with a lower count. For those with a higher neutrophil-to-lymphocyte ratio, the chance of dying was 48% higher.

“A higher peripheral blood neutrophil and lower lymphocyte counts might be a reflection of pathological immune processes in systemic sclerosis, and a marker for more severe disease,” the researchers wrote.

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To confirm their findings, the researchers drew on data from the Scleroderma Lung Study (SLS) II (NCT00883129), which included 142 patients with SSc receiving experimental treatment with either mycophenolate mofetil or cyclophosphamide followed by a placebo. Of those, 134 (94.4%) had available blood neutrophil and lymphocyte counts.

Similar to GENISOS, higher numbers in neutrophil counts and neutrophil-to-lymphocyte ratios in SLSII also predicted more severe disease over time and worse mortality.

“These results provide direct clinical support for a pathological role of neutrophils both independently and possibly via interaction with lymphocytes in SSc,” the researchers concluded.