Blood globulin levels at diagnosis may predict survival with AAV
Large data study finds 2.6 times higher risk of death with higher levels
Blood levels of globulins — a group of proteins that includes antibodies — when ANCA-associated vasculitis (AAV) is diagnosed can help in forecasting the risk of a patient dying of any cause, a large data study from Korea suggests.
“The present study is the first to demonstrate that [total globulin fraction] at AAV diagnosis can forecast all-cause mortality during the disease course in AAV patients,” the researchers wrote, adding that fraction is thought “to reflect the extent of various immune reactions as well as the degree of inflammatory burden.”
The study, “Total Globulin Fraction at Diagnosis Could Forecast All-Cause Mortality during the Disease Course in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis,” was published in the Journal of Clinical Medicine.
Globulins are blood proteins, mostly inflammation markers and antibodies
In AAV, the immune system mistakenly produces self-reactive antibodies, called ANCAs, that ultimately lead to inflammation and damage to small blood vessels.
Globulins, which make up a large part of proteins in blood, fall into three main classes: alpha, beta, and gamma. Most alpha globulins are inflammation markers that peak during times of inflammation, while most gamma globulins are antibodies, or immunoglobulins, that are involved in immune responses.
While previous studies suggested that a higher inflammatory burden is linked to poorer survival in AAV patients, whether globulin levels have a similar predictive value remains unknown.
Researchers in South Korea tested if the total globulin fraction could predict how likely it is for a person to die of any cause during the course of AAV. The total globulin fraction is calculated by removing the level of albumin, the most abundant protein in blood, from total protein levels.
Their study involved 283 patients (182 women and 101 men), all taking part in an observational study that included their full medical records at the time of AAV diagnosis. The group had a median age of 60, and all were followed for at least three months after diagnosis.
More than half (54.8%) had microscopic polyangiitis, the most common type of AAV. One-quarter of the patients (25.4%) had granulomatosis with polyangiitis, and 56 (19.8%) had eosinophilic granulomatosis with polyangiitis, the rarest type.
Patients’ median body mass index (BMI), a measure of body fat based on height and weight, was 22.7, which was within the normal range.
Almost half (40.3%) had high blood pressure, 26.5% had type 2 diabetes, and 20.5% had an abnormal level of fats in the blood; all are considered to be risk factors of mortality.
At the time of diagnosis, the group’s median total globulin fraction was 2.9 grams per deciliter of blood (g/dL); the range was 2.6 to 3.4 g/dL.
The median total globulin fraction was significantly higher among patients who tested positive for ANCAs than among those without these antibodies (3 vs. 2.8 g/dL). A higher the total globulin fraction also linked with a higher the erythrocyte sedimentation rate and C-reactive protein level, two markers of inflammation.
However, the total globulin fraction showed no association with the Birmingham Vasculitis Activity Score, a measure of AAV activity, or the five-factor score, a tool used to assess AAV patients’ prognosis.
These findings suggest that globulin levels may reflect “the degree of inflammatory burden rather than AAV activity or prognostic indices,” the researchers wrote.
Calculating life expectancy with ANCA-associated vasculitis
Over a median follow-up of nearly four years (46.9 months), 39 patients (13.8%) died. Those with a total globulin fraction equal to or greater than 3.1 g/dL at the time of diagnosis were significantly more likely to die during that period relative to those with lower values.
Further statistical analyses, accounting for potential influencing factors, showed that having a total globulin fraction of at least 3.1 g/dL significantly increased by 2.6 times the risk of dying from any cause.
This finding held even considering comorbidities (co-occurring conditions) taken as “risk factors for death in the general population,” the team wrote, further supporting total globulin fraction’s potential as a predictor of survival.
Male sex also was a strong and independent risk factor of all-cause mortality, being linked to a three times greater risk of death. Older age and a higher BMI also influenced the risk of death, but to a lesser extent.
Study findings “suggest that TGF [total globulin fraction] at AAV diagnosis may be useful in forecasting all-cause mortality during the disease course in AAV patients,” the researchers wrote.
“As patients with infectious diseases and immunoglobulin-producing [blood cancers] at AAV diagnosis were excluded from the present study … a high level of TGF at AAV diagnosis might be associated with immunoglobulins that are produced due to dysregulated immune tolerance, such as [self-reactive antibodies],” they added.
They also noted that “TGF should be calculated at AAV diagnosis and more attention should be paid to AAV patients when TGF calculated at AAV diagnosis is above the cut-off value” of 3.1 g/dL.
Larger studies, following patients over time, are needed to “provide more reliable and clearer information on the role of TGF calculated at AAV diagnosis in forecasting all-cause mortality in AAV patients,” the team concluded.
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