Association of Persistent Symptoms after Lyme Neuroborreliosis and Increased Levels of Interferon-α in Blood

Abstract

Patients who have Lyme neuroborreliosis (LNB) might experience lingering symptoms that persist despite antibiotic drug therapy. We tested whether those symptoms are caused by maladaptive immune responses by measuring 20 immune mediators in serum and cerebrospinal fluid (CSF) in 79 LNB patients followed for 1 year. At study entry, most mediators were highly concentrated in CSF, the site of the infection. Those responses resolved with antibiotic therapy, and associations between CSF cytokines and signs and symptoms of LNB were no longer observed. In contrast, subjective symptoms that persisted after use of antibiotics were associated with increased levels of serum interferon-α (IFN-α), which were already observed at study entry, and remained increased at each subsequent timepoint. Highest IFN-α levels corresponded with severe disease. Although the infection serves as the initial trigger, sequelae after antibiotic therapy are associated with unremitting systemic IFN-α levels, consistent with the pathogenic role of this cytokine in interferonopathies in other conditions.

Neuropsychiatric Lyme Disease and Vagus Nerve Stimulation

“…Studies have shown multiple elevated immune markers in both acute Lyme disease (IL-6, IL-8, IL-12, IL-18, IFN-γ, CXCL12, CXCL13) and PTLDS (IL-6, IL-23, IFN-α, CCL19) [ 46 , 47 , 48 , 49 ]. A recent study indicated that in patients with acute neuroborreliosis whose symptoms persisted despite antibiotic therapy, serum IFN-α remained elevated from the initial testing at the onset of acute neurologic infection to each of the subsequent post-antibiotic treatment timepoints, with the highest levels corresponding to severe disease [ 50 ]. This finding, complemented by the observation that IFN-α levels were elevated in the CSF but then returned to normal after antibiotic therapy, supports the possibility that initial infection with Borrelia burgdorferi serves as a trigger for persistent symptoms due to an interferonopathy.…”

Annexin A2 antibodies in post-treatment Lyme disease

“…T-cell reactivity and antibody development after acute LD are of particular interest in the setting of post-treatment Lyme disease (PTLD), an infection-associated chronic illness of poorly understood etiology, and there is growing evidence that upregulation of interferons after early stages of LD may be associated with PTLD pathogenesis. 3 , 4 …”

Investigation of Possible Link Between Interferon-α and Lyme Disease

“…To the Editor: We were intrigued by Hernandez et al’s recent important study linking persistent subjective symptoms after Lyme neuroborreliosis in Europe with increased interferon (IFN) α levels in blood ( 1 ). Their findings align with our earlier study in the United States, which showed an association between persistent objective neurocognitive deficits, despite antibiotic treatment for Lyme disease, and elevated blood IFN-α activity ( 2 ).…”

“…A noteworthy difference between the 2 studies is the method of IFN-α detection. Hernandez et al ( 1 ) relied on a bead-based immunoassay to directly measure IFN-α levels, whereas we used a functional cell-based assay and quantitative real-time PCR to assess IFN-α activity ( 2 , 3 ). Direct quantitation of IFN-α can be challenging, as highlighted by the fact that concentrations for some study participants in the Hernandez et al article appeared to fall below the limit of quantitation, thus complicating the analysis and interpretation of the data.…”