Immune cell count predicts EGPA peripheral nerve damage risk
Measuring eosinophils can show presence, severity of peripheral neuropathy
Measuring immune cells called eosinophils can help predict the presence and severity of peripheral neuropathy (damage to nerves outside the brain and spinal cord) in people with eosinophilic granulomatosis with polyangiitis (EGPA), a study showed.
In people with one of the other two types of ANCA-associated vasculitis (AAV) — granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) — more severe peripheral neuropathy tended to be linked to higher numbers of neutrophils relative to lymphocytes (two types of immune cells).
“Early recognition and treatment initiation for peripheral neuropathy is important to prevent irreversible organ damage, and our data suggest that blood eosinophil counts or neutrophil-to-lymphocyte ratio are useful to predict the presence and severity of peripheral neuropathy in patients with ANCA-associated vasculitis,” the researchers wrote.
The study, “Distinct predictors of peripheral neuropathy in antineutrophil cytoplasmic antibody-associated vasculitis: KEIO-vasculitis cohort,” was published in Seminars in Arthritis and Rheumatism by four researchers in Japan.
Most cases of AAV are associated with the production of self-reactive antibodies called ANCAs, which target healthy proteins in neutrophils, ultimately causing them to malfunction and attack the lining of small blood vessels.
Neuropathy affects quality of life
EGPA, the rarest type of AAV, is less frequently associated with ANCAs than GPA or MPA, but is marked by high levels of eosinophils.
Peripheral neuropathy, which can affect movement and sensation, is among the “clinical manifestations of ANCA-associated vasculitis and can be a presenting symptom,” the researchers wrote, adding that this type of damage “has a major impact on patients’ quality of life.”
Early diagnosis of peripheral neuropathy is important because “nerve recovery is slow and sometimes partial,” the researchers wrote. “Identifying baseline [initial] factors associated with peripheral neuropathy may aid in early recognition and treatment initiation.”
With this in mind, the team retrospectively analyzed data from 111 people newly diagnosed with active AAV — 45 had MPA, 40 had GPA, and 26 had EGPA — and had not yet started treatment.
At diagnosis (baseline), peripheral neuropathy was present in 43 patients (38.7%), including 25 with sensorimotor neuropathy, a more severe form that affects both movement and sensation.
Of the 18 patients with pure sensory neuropathy, which affects sensation and typically causes symptoms such as numbness, tingling, or sharp and burning pain, 11 also showed damage to nerves controlling movement on objective tests; however, this did not result in obvious motor symptoms.
Peripheral neuropathy was significantly more common among people with EGPA (84.6%) than in those with GPA (20%) or MPA (28.9%). A similar pattern was observed for sensorimotor neuropathy (57.7% vs. 15% and 8.9%).
Participants without peripheral neuropathy were significantly older (median age 74) than those with sensory neuropathy (median age 67) and those with sensorimotor neuropathy (median age 62). The absence of peripheral neuropathy was also associated with lower counts of eosinophils and overall immune cells.
People with sensorimotor neuropathy were significantly more likely to receive high-dose corticosteroids, a type of anti-inflammatory treatment, and intravenous immunoglobulin, an infusion of antibodies from healthy donors that can neutralize ANCAs, than those with sensory neuropathy and those without peripheral neuropathy.
“Despite this intensive treatment, neurological recovery was limited,” the researchers wrote, adding that complete nerve recovery after one year was reported in 30% of those with sensorimotor neuropathy and one patient with sensory neuropathy.
All six patients who experienced complete motor function recovery had EGPA.
More eosinophils linked to more severe peripheral neuropathy
In EGPA patients, higher numbers of eosinophils at baseline were associated with more severe peripheral neuropathy. Those without peripheral neuropathy had about half the eosinophils of those with sensory neuropathy (2,340 vs. 4,276 eosinophils per microliter of blood) and five times fewer than those with sensorimotor neuropathy (2,340 vs. 11,859 eosinophils per microliter of blood).
The team then aimed to identify cutoff points for predicting peripheral and sensorimotor neuropathy in EGPA. A cutoff of 2,468 eosinophils per microliter of blood allowed researchers to discriminate between patients with any type of peripheral neuropathy and those without, with an accuracy of 85%. A cutoff value of 6,724 predicted sensorimotor neuropathy with a similar level of accuracy.
For GPA and MPA, the pattern was different. Instead of eosinophils, peripheral neuropathy appeared to be associated with the neutrophil-to-lymphocyte ratio. This ratio tended to increase as peripheral neuropathy became more severe in these two patient groups, but the change was not strong enough to be statistically significant.
“These results highlight the distinct immunological mechanisms underlying neuropathy in ANCA-associated vasculitis subtypes,” the team wrote.
The findings suggest that “blood eosinophil counts at baseline may be useful to predict the presence and severity of peripheral neuropathy in patients with newly diagnosed EGPA,” the team wrote. In contrast, the researchers said, “neutrophils may play a central role in the [development] of peripheral neuropathy in GPA and MPA, but this relationship remains inconclusive.”
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