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Gabriella True

Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection

Brian A.Fallon, BarbaraStrobino, SeanReim, JulieStoner, Madeleine W.Cunningham Brain, Behavior, & Immunity – Health, Volume 2, February 2020, 100015. https://doi.org/10.1016/j.bbih.2019.100015

This study examines molecular mimicry targeting neural tissue after Borrelia burgdorferi (Bb) infection. Patients with Lyme disease have a greater frequency of specific anti-neuronal autoantibodies and functional neuronal activation compared to community controls without a history of Lyme disease.

“Highlights

• The EM ​+ ​prior LD group had significantly elevated anti-neuronal antibodies.
• The EM ​+ ​prior LD group had significantly elevated CaM Kinase activation.
• Anti-Lysoganglioside Antibodies are significantly elevated in the PTLS group.
• Prior infection may lead to immune priming and increased autoantibodies.”

Ajmone-Cat MA, Spinello C, Valenti D, Franchi F, Macrì S, Vacca RA, Laviola G. Journal of Clinical Medicine. 2019; 8(10):1514. DOI: 10.3390/jcm8101514

• Adverse psychosocial experiences have been shown to modulate individual responses to immune challenges and affect mitochondrial functions.
• Results show chronic psychosocial stress altered the expression of neuroinflammatory markers in the hippocampal and hypothalamic regions, exacerbated the neuroinflammatory alterations induced by experimental GAS exposures in the same areas.
• Psychosocial stress exacerbated individual response to GAS administrations whereby mice exposed to both treatments exhibited altered cytokine and immune-related enzyme expression in the hippocampus and hypothalamus.
• Showed impaired mitochondrial respiratory chain complexes IV and V, and reduced adenosine triphosphate (ATP) production by mitochondria and ATP content.
• These brain abnormalities, observed in GAS-Stress mice, were associated with blunted titers of plasma corticosterone.
• Present data support the hypothesis that challenging environmental conditions, in terms of chronic psychosocial stress, may exacerbate the long-term consequences of exposure to GAS processes through the promotion of central immunomodulatory and oxidative stress.

Platt, Maryann P.
Columbia Academic Commons-2019 Theses Doctoral

Taken together, these data demonstrate the pivotal role of Th17 lymphocytes in brain pathology and olfactory processing deficits after recurrent GAS infections in our mouse model. Our intranasal inoculation model supports the conclusion that post-infectious BGE is autoimmune in nature, despite the absence of behavioral symptoms in this model. Using multiple mouse models of post-infectious BGE may allow us to study distinct facets of disease pathogenesis. Finally, this work underscores the ability of T cells to incite neuroinflammation, provides a useful clinical diagnostic test in olfactory functional assessments, and lends support to T cell immunotherapy strategies in patients with post-infectious BGEs.

Madeleine W. Cunningham
Microbiology Spectrum-August 2019
Author manuscript – In advance of print

The studies suggest 1) that the antibodies against streptococci and brain in Sydenham chorea and related diseases produce CNS dysfunction through a neuronal signal transduction and subsequent excess dopamine release mechanism and 2) that the molecular targets of the chorea antibodies include lysoganglioside and the dopamine receptors in neuronal cell membranes. The anti-neuronal autoantibodies also target the group A streptococcal carbohydrate epitope N-acetyl beta-D-glucosamine present on the rhamnose backbone of the carbohydrate and present in the cell membrane and wall of the group A streptococci as well as the intracellular brain protein tubulin. The diagram in Figure 15 illustrates proposed events of how antineuronal autoantibodies against lysoganglioside and the dopamine receptors D1 and D2 may function in Sydenham chorea and PANDAS (3).