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, 24 (6), 1018-24

Anti-neural Antibody Reactivity in Patients With a History of Lyme Borreliosis and Persistent Symptoms

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Anti-neural Antibody Reactivity in Patients With a History of Lyme Borreliosis and Persistent Symptoms

Abhishek Chandra et al. Brain Behav Immun.

Abstract

Some Lyme disease patients report debilitating chronic symptoms of pain, fatigue, and cognitive deficits despite recommended courses of antibiotic treatment. The mechanisms responsible for these symptoms, collectively referred to as post-Lyme disease syndrome (PLS) or chronic Lyme disease, remain unclear. We investigated the presence of immune system abnormalities in PLS by assessing the levels of antibodies to neural proteins in patients and controls. Serum samples from PLS patients, post-Lyme disease healthy individuals, patients with systemic lupus erythematosus, and normal healthy individuals were analyzed for anti-neural antibodies by immunoblotting and immunohistochemistry. Anti-neural antibody reactivity was found to be significantly higher in the PLS group than in the post-Lyme healthy (p<0.01) and normal healthy (p<0.01) groups. The observed heightened antibody reactivity in PLS patients could not be attributed solely to the presence of cross-reactive anti-borrelia antibodies, as the borrelial seronegative patients also exhibited elevated anti-neural antibody levels. Immunohistochemical analysis of PLS serum antibody activity demonstrated binding to cells in the central and peripheral nervous systems. The results provide evidence for the existence of a differential immune system response in PLS, offering new clues about the etiopathogenesis of the disease that may prove useful in devising more effective treatment strategies.

Conflict of interest statement

Conflict of interest statement

All authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Pattern of antibody reactivity in the serum of representative PLS patients and control subjects towards electrophoresis-separated and transferred brain proteins. A) PLS patients P1-P6; B) post-Lyme healthy individuals H1-H6 (H1-H4 had presented with single EM, while H5 and H6 had presented with multiple EM); C) systemic lupus erythematosus patients S1-S6; D) normal healthy individuals N1-N6. Lane C in each panel is the positive control. Molecular weight markers are indicated to the left of each panel (kDa).
Figure 2
Figure 2
Mean total anti-brain antibody reactivity in patient and control groups. A) Comparison between PLS patients, post-Lyme healthy subjects, normal healthy subjects without serologic evidence of prior Lyme disease, and patients with systemic lupus erythematosus. Reactivity was significantly higher in the PLS group than in post-Lyme healthy (p<0.001) and normal healthy (p<0.001) groups. B) Comparison between seropositive and seronegative patients in PLS and post-Lyme healthy groups. PLS seropositive and seronegative subgroups had significantly higher anti-brain antibody reactivity than their counterparts in the post-Lyme healthy group (p<0.005). The difference between PLS seropositive and seronegative patients did not reach statistical significance. Error bars represent the standard error of the mean. Groups indicated by different superscripts are significantly different from one another.
Figure 3
Figure 3
Immunohistochemical analysis of serum antibody reactivity towards cells in the brain cerebral cortex (left panel) and DRG (right panel). A) Staining of sections with serum from borrelial seropositive (A1) and borrelial seronegative (A2) patients with anti-neural antibody reactivity (as determined by immunoblotting) showed specific binding to neurons of the cerebral cortex and the DRG. B) Staining of sections with serum from borrelial seropositive (B1) and borrelial seronegative (B2) post-Lyme healthy individuals with anti-neural antibody reactivity showed faint or no specific binding of antibodies to cerebral cortex and DRG tissues. C) Serum antibodies from two representative SLE patients (C1 and C2) with anti-neural antibody reactivity bound strongly to neurons and glial cells in the cerebral cortex and the DRG. D) Sera from two normal healthy subjects (D1 and D2) did not stain tissues specifically. Bars = 50 µm.
Figure 4
Figure 4
Cross-reactivity of the anti-borrelia immune response in immunized rabbits towards neural proteins. A, B) One- and two-dimensional immunoblots of mouse brain lysate with rabbit affinity-purified anti-borrelia antibody indicated cross-reactivity towards several neural proteins. Numbers to the left of each panel indicate molecular weight markers (kDa). C, D) Immunohistochemical analysis of the interaction of affinity-purified anti-borrelia antibodies with human cerebral cortex (C) and DRG (D) showed binding to neurons and glial cells. Bars = 50 µm.

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