Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection
Background: Molecular mimicry targeting neural tissue has been reported after Borrelia burgdorferi(Bb) infection. Herein, we investigate whether antineuronal autoantibodies are increased and whether antibody-mediated signaling of neuronal cells is elevated in a cohort of symptomatic adults with a hi...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | Brain, Behavior, & Immunity - Health |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354619300158 |
| _version_ | 1818664295100055552 |
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| author | Brian A. Fallon Barbara Strobino Sean Reim Julie Stoner Madeleine W. Cunningham |
| author_facet | Brian A. Fallon Barbara Strobino Sean Reim Julie Stoner Madeleine W. Cunningham |
| author_sort | Brian A. Fallon |
| collection | DOAJ |
| description | Background: Molecular mimicry targeting neural tissue has been reported after Borrelia burgdorferi(Bb) infection. Herein, we investigate whether antineuronal autoantibodies are increased and whether antibody-mediated signaling of neuronal cells is elevated in a cohort of symptomatic adults with a history of Lyme Disease (LD). Methods: Participants (n = 179) included 24 with recent Erythema Migrans (EM) without prior LD, 8 with recent EM and prior LD (EM + prior LD), 119 with persistent post-treatment LD symptoms (PTLS), and 28 seronegative endemic controls with no prior LD history. Antineuronal immunoglobulin G (IgG) titers were measured by standard ELISA and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was identified in serum. Results: EM + prior LD cases had higher antibody titers than controls for anti-lysoganglioside GM1 (p = 0.002), anti-tubulin (p = 0.03), and anti-D1R (p = 0.02), as well as higher expression in the functional antibody-mediated CaMKII Assay (p = 0.03). The EM cases with no prior history showed no significant differences on any measures. The PTLS cases demonstrated significantly higher titers (p = 0.01) than controls on anti-lysoganglioside GM1, but not for the other measures. Conclusion: The finding of elevated anti-neuronal autoantibodies in our small sample of those with a prior history of Lyme disease but not in those without prior Lyme disease, if replicated in a larger sample, suggests an immune priming effect of repeated infection; the CaMKII activation suggests that antineuronal antibodies have functional significance. The elevation of anti-lysoganglioside antibodies among those with PTLS is of particular interest given the established role of anti-ganglioside antibodies in peripheral and central neurologic diseases. Future prospective studies can determine whether these autoantibodies emerge after Bb infection and whether their emergence coincides with persistent neurologic or neuropsychiatric symptoms. |
| first_indexed | 2024-12-17T05:30:28Z |
| format | Article |
| id | doaj.art-9edd3f2e27ed425ea3b481986510b651 |
| institution | Directory Open Access Journal |
| issn | 2666-3546 |
| language | English |
| last_indexed | 2024-12-17T05:30:28Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj.art-9edd3f2e27ed425ea3b481986510b6512022-12-21T22:01:45ZengElsevierBrain, Behavior, & Immunity - Health2666-35462020-02-012100015Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infectionBrian A. Fallon0Barbara Strobino1Sean Reim2Julie Stoner3Madeleine W. Cunningham4Columbia Psychiatry, Columbia University Irving Medical Center, New York, USA; New York State Psychiatric Institute, 1051 Riverside Drive, New York, USA; Corresponding author. Columbia University, 1051 Riverside Drive, Unit 69, New York, NY, 10032, USA.Columbia Psychiatry, Columbia University Irving Medical Center, New York, USA; New York State Psychiatric Institute, 1051 Riverside Drive, New York, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, USADepartment of Biostatistics, University of Oklahoma Health Sciences Center, Oklahoma City, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, USABackground: Molecular mimicry targeting neural tissue has been reported after Borrelia burgdorferi(Bb) infection. Herein, we investigate whether antineuronal autoantibodies are increased and whether antibody-mediated signaling of neuronal cells is elevated in a cohort of symptomatic adults with a history of Lyme Disease (LD). Methods: Participants (n = 179) included 24 with recent Erythema Migrans (EM) without prior LD, 8 with recent EM and prior LD (EM + prior LD), 119 with persistent post-treatment LD symptoms (PTLS), and 28 seronegative endemic controls with no prior LD history. Antineuronal immunoglobulin G (IgG) titers were measured by standard ELISA and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was identified in serum. Results: EM + prior LD cases had higher antibody titers than controls for anti-lysoganglioside GM1 (p = 0.002), anti-tubulin (p = 0.03), and anti-D1R (p = 0.02), as well as higher expression in the functional antibody-mediated CaMKII Assay (p = 0.03). The EM cases with no prior history showed no significant differences on any measures. The PTLS cases demonstrated significantly higher titers (p = 0.01) than controls on anti-lysoganglioside GM1, but not for the other measures. Conclusion: The finding of elevated anti-neuronal autoantibodies in our small sample of those with a prior history of Lyme disease but not in those without prior Lyme disease, if replicated in a larger sample, suggests an immune priming effect of repeated infection; the CaMKII activation suggests that antineuronal antibodies have functional significance. The elevation of anti-lysoganglioside antibodies among those with PTLS is of particular interest given the established role of anti-ganglioside antibodies in peripheral and central neurologic diseases. Future prospective studies can determine whether these autoantibodies emerge after Bb infection and whether their emergence coincides with persistent neurologic or neuropsychiatric symptoms.http://www.sciencedirect.com/science/article/pii/S2666354619300158Lyme diseaseAntineuronal antibodiesLysogangliosideCaMKinase II |
| spellingShingle | Brian A. Fallon Barbara Strobino Sean Reim Julie Stoner Madeleine W. Cunningham Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection Brain, Behavior, & Immunity - Health Lyme disease Antineuronal antibodies Lysoganglioside CaMKinase II |
| title | Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection |
| title_full | Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection |
| title_fullStr | Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection |
| title_full_unstemmed | Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection |
| title_short | Anti-lysoganglioside and other anti-neuronal autoantibodies in post-treatment Lyme Disease and Erythema Migrans after repeat infection |
| title_sort | anti lysoganglioside and other anti neuronal autoantibodies in post treatment lyme disease and erythema migrans after repeat infection |
| topic | Lyme disease Antineuronal antibodies Lysoganglioside CaMKinase II |
| url | http://www.sciencedirect.com/science/article/pii/S2666354619300158 |
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