Blood biomarkers of inflammation may aid AAV assessment: Study
Researchers say novel markers may be cheap and efficient new tool
Ratios of different kinds of blood cells, reflecting inflammation and immune activity, may be a cheap and efficient tool to aid in the diagnosis of ANCA-associated vasculitis (AAV), and in predicting disease activity, a new study from China reports.
“While not standalone diagnostic tools, these markers offer valuable support to standard AAV assessment, particularly in challenging cases,” the researchers wrote.
With routine blood testing, clinicians can calculate these ratios. In addition to accurately distinguishing between people with and without AAV, many of these metrics also correlated with disease activity, degree of organ involvement, and estimated prognosis.
“Their accessibility suggests potential for enhancing clinical management” of AAV, the team noted.
Titled “The diagnostic and prognostic role of novel biomarkers in anti-neutrophil cytoplasmic antibody-associated vasculitis,” the study was published in the journal Frontiers in Immunology.
AAV typically occurs when self-reactive antibodies called ANCAs lead to the overactivation of neutrophils, a type of immune cell. This causes inflammation and damage to small blood vessels.
Other types of immune cells — such as lymphocytes, which can produce antibodies and kill other damaged or infected cells, and monocytes, which clean up damaged cells — may also contribute to this response.
Diagnosing AAV can be challenging
It can be a challenge for clinicians to diagnose AAV, because its symptoms can vary widely depending on the impacted organs or tissues. Complicating this further, about 10% to 20% of people with AAV don’t have elevated ANCA levels in testing.
“These limitations highlight the need for additional tools to support the diagnostic process and enhance disease assessment,” the researchers wrote.
Ratios of blood cells, “such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), have emerged as promising indicators of inflammation in various autoimmune and inflammatory conditions,” the team noted.
Platelets are the cell fragments in blood that are involved in blood clotting. The SII considers platelets, neutrophils, and lymphocytes, and the SIRI considers neutrophils, monocytes, and lymphocytes.
In prior studies, people with AAV have been reported to have high NLR and PLR, but the role of the other three inflammatory markers remains unclear.
According to the team, these markers “may serve as supportive tools to complement established diagnostic methods and aid in disease monitoring.”
Researchers focus on 5 markers of inflammation
In this study, a research team from Peking University International Hospital in Beijing further analyzed these five markers of inflammation in 65 AAV patients and 65 age- and sex-matched people without autoimmune or inflammatory disease diagnoses.
The AAV patients had a mean age of 66, and had lived with the disease for a mean of 30.6 months, or about 2.5 years. Slightly more than half (55.4%) had granulomatosis with polyangiitis, with microscopic polyangiitis as the next most common AAV type.
The team also examined, for the AAV participants, clinical assessments of disease activity, organ involvement, irreversible organ damage, and estimated mortality risk.
Each of the five inflammatory markers was significantly higher in the AAV group than in the control group. Using specific cutoff values, the team found that each marker was able to effectively distinguish people with AAV from healthy controls. SIRI showed the best discriminating potential, with an accuracy of 90.2%.
These tests showed a sensitivity, or a percentage of AAV cases being correctly identified, that ranged from 64.4% to 84.7%. Their specificity, or the percentage of unaffected cases being correctly ruled out, was 83.1% to 100%.
Although NLR had the highest specificity, it had one of the lowest sensitivities, the data showed. SII and SIRI more evenly balanced these metrics, indicating their potential for use in diagnoses, the team noted.
“This study demonstrates for the first time that SIRI holds significant value in differentiating AAV from healthy individuals,” the researchers wrote. It also further supports the potential role of NLR and PLR, and adds MLR and SII as possible indicators.
Higher blood biomarker values linked to more disease activity
People with AAV were also separated into those with active disease and nonactive disease. All markers, except MLR, were significantly higher in the active disease group, and also showed a lower discriminating ability, with a sensitivity ranging from 59.5% to 81.1%, and a specificity from 63.6% to 86.4%.
“Their moderate sensitivity and specificity suggest they should be interpreted alongside clinical assessments rather than as standalone predictors,” the team wrote.
Also, higher values of each marker, except MLR, were significantly associated with greater disease activity and worse disease prognosis, indicating a greater risk of death. All metrics also correlated significantly with the extent of organ involvement, predicted using a clinical test.
[These markers,] derived from routine blood counts … provide a cost-effective, accessible tool to enhance diagnostic workflows, especially in resource-limited settings. … Integrating these markers with other biomarkers … could optimize their supportive utility in AAV management.
None of the markers, however, correlated with tests estimating organ and tissue damage from AAV and treatment. Per the researchers, this suggests that “these markers are more attuned to acute inflammation than chronic, treatment-related damage.”
Altogether, these findings indicate that these markers, “derived from routine blood counts … provide a cost-effective, accessible tool to enhance diagnostic workflows, especially in resource-limited settings,” the team wrote. “Integrating these markers with other biomarkers (e.g., ANCA titers … ) could optimize their supportive utility in AAV management.”
Because the study was retrospective, meaning participants’ medical records were examined after the fact, the researchers could not assess how the markers related to subsequent clinical outcomes.
“Future [follow-up] studies are needed to investigate the predictive value of these biomarkers for treatment response,” the team concluded.
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