Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits

Abstract

Following antibiotic treatment for Lyme disease, some patients report persistent or relapsing symptoms of pain, fatigue, and/or cognitive deficits. Factors other than active infection, including immune abnormalities, have been suggested, but few clues regarding mechanism have emerged. Furthermore, the effect of antibiotic treatment on immune response in affected individuals remains unknown. In this study, a longitudinal analysis of specific immune markers of interest was carried out in patients with a history of Lyme disease and persistent objective memory impairment, prior to and following treatment with either ceftriaxone or placebo. IFNα activity was measured by detection of serum-induced changes in specific target genes, using a functional cell-based assay and quantitative real-time PCR. Level and pattern of antibody reactivity to brain antigens and to Borrelia burgdorferi proteins were analyzed by ELISA and immunoblotting. Sera from the patient cohort induced significantly higher expression of IFIT1 and IFI44 target genes than those from healthy controls, indicating increased IFNα activity. Antibody reactivity to specific brain and borrelial proteins was significantly elevated in affected patients. IFNα activity and antibody profile did not change significantly in response to ceftriaxone. The heightened antibody response implies enhanced immune stimulation, possibly due to prolonged exposure to the organism prior to the initial diagnosis and antibiotic treatment of Lyme disease. The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms.

Genetic Control of Lyme Arthritis by Borrelia burgdorferi Arthritis–Associated Locus 1 Is Dependent on Localized Differential Production of IFN-β and Requires Upregulation of Myostatin

“…Our finding of a pathologic type I IFN profile is consistent with several publications that have shown a type I IFN signature in the serum of human Lyme patients at stages of active disease (2, 24) and in the synovial fluid of treatment-refractory RA patients (25). Arthritis is also a transient side effect in hepatitis C and multiple sclerosis patients treated with IFN-α/β (26, 27), further supporting the linkage between elevated levels of type I IFN and arthritis.…”

“…Disease outcomes range from acute to chronic, sometimes resulting in irreversible damage to the nervous (2) and cardiovascular (3, 4) systems. Arthritis is the most common late disease manifestation (5), affecting up to 60% of patients and persisting in 10% of patients despite antibiotic therapy (6).…”

Estimation of cognitive and affective disorders occurrence in patients with Lyme borreliosis

“…They are considered to be connected with immunological, toxic and metabolic processes which take place in the involved system [24,25,26].…”

Borrelia burgdorferi Arthritis–Associated Locus Bbaa1 Regulates Lyme Arthritis and K/B×N Serum Transfer Arthritis through Intrinsic Control of Type I IFN Production

“…Type I IFNs have also been identified in patients with various manifestations of Lyme disease, including skin lesions and cognitive deficits (63, 64), and have been implicated in B lymphocyte accumulation in the lymph nodes of infected mice (65). Taken in context with these previous findings, the current genetic identification of Bbaa1 implicates the cluster encoding the IFNαβ genes as a candidate regulator of Lyme arthritis.…”