Host glycosylation of immunoglobulins impairs the immune response to acute Lyme diseaseResearch in context
Summary: Background: Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396424000148 |
| _version_ | 1797347108709203968 |
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| author | Benjamin S. Haslund-Gourley Jintong Hou Kyra Woloszczuk Elizabeth J. Horn George Dempsey Elias K. Haddad Brian Wigdahl Mary Ann Comunale |
| author_facet | Benjamin S. Haslund-Gourley Jintong Hou Kyra Woloszczuk Elizabeth J. Horn George Dempsey Elias K. Haddad Brian Wigdahl Mary Ann Comunale |
| author_sort | Benjamin S. Haslund-Gourley |
| collection | DOAJ |
| description | Summary: Background: Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections and people with a recent history of antibiotic-treated Lyme disease. Methods: Machine learning technology was utilized to improve the prediction of acute Lyme disease and identify sialic acid and galactose sugar structures (N-glycans) on immunoglobulins associated specifically at time points during acute Lyme disease time. A plate-based approach was developed to analyze sialylated N-glycans associated with anti-Bb immunoglobulins. This multiplexed approach quantitates the abundance of Bb-specific IgG and the associated sialic acid, yielding an accuracy of 90% in a powered study. Findings: It was demonstrated that immunoglobulin sialic acid levels increase during acute Lyme disease and following antibiotic therapy and a 3-month convalescence, the sialic acid level returned to that found in healthy control subjects (p < 0.001). Furthermore, the abundance of sialic acid on Bb-specific IgG during acute Lyme disease impaired the host’s ability to combat Lyme disease via lymphocytic receptor FcγRIIIa signaling. After enzymatically removing the sialic acid present on Bb-specific antibodies, the induction of cytotoxicity from acute Lyme disease patient antigen-specific IgG was significantly improved. Interpretation: Taken together, Bb-specific immunoglobulins contain increased sialylation which impairs the host immune response during acute Lyme disease. Furthermore, this Bb-specific immunoglobulin sialyation found in acute Lyme disease begins to resolve following antibiotic therapy and convalescence. Funding: Funding for this study was provided by the Coulter-Drexel Translational Research Partnership Program as well as from a Faculty Development Award from the Drexel University College of Medicine Institute for Molecular Medicine and Infectious Disease and the Department of Microbiology and Immunology. |
| first_indexed | 2024-03-08T11:42:38Z |
| format | Article |
| id | doaj.art-981e46392c30401ba0e4d12812146b6f |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-08T11:42:38Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-981e46392c30401ba0e4d12812146b6f2024-01-25T05:23:07ZengElsevierEBioMedicine2352-39642024-02-01100104979Host glycosylation of immunoglobulins impairs the immune response to acute Lyme diseaseResearch in contextBenjamin S. Haslund-Gourley0Jintong Hou1Kyra Woloszczuk2Elizabeth J. Horn3George Dempsey4Elias K. Haddad5Brian Wigdahl6Mary Ann Comunale7Department of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USADepartment of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USADepartment of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USALyme Disease Biobank, Portland, Oregon, USAEast Hampton Family Medicine, East Hampton North, New York, USADepartment of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USADepartment of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USADepartment of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA; Corresponding author.Summary: Background: Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections and people with a recent history of antibiotic-treated Lyme disease. Methods: Machine learning technology was utilized to improve the prediction of acute Lyme disease and identify sialic acid and galactose sugar structures (N-glycans) on immunoglobulins associated specifically at time points during acute Lyme disease time. A plate-based approach was developed to analyze sialylated N-glycans associated with anti-Bb immunoglobulins. This multiplexed approach quantitates the abundance of Bb-specific IgG and the associated sialic acid, yielding an accuracy of 90% in a powered study. Findings: It was demonstrated that immunoglobulin sialic acid levels increase during acute Lyme disease and following antibiotic therapy and a 3-month convalescence, the sialic acid level returned to that found in healthy control subjects (p < 0.001). Furthermore, the abundance of sialic acid on Bb-specific IgG during acute Lyme disease impaired the host’s ability to combat Lyme disease via lymphocytic receptor FcγRIIIa signaling. After enzymatically removing the sialic acid present on Bb-specific antibodies, the induction of cytotoxicity from acute Lyme disease patient antigen-specific IgG was significantly improved. Interpretation: Taken together, Bb-specific immunoglobulins contain increased sialylation which impairs the host immune response during acute Lyme disease. Furthermore, this Bb-specific immunoglobulin sialyation found in acute Lyme disease begins to resolve following antibiotic therapy and convalescence. Funding: Funding for this study was provided by the Coulter-Drexel Translational Research Partnership Program as well as from a Faculty Development Award from the Drexel University College of Medicine Institute for Molecular Medicine and Infectious Disease and the Department of Microbiology and Immunology.http://www.sciencedirect.com/science/article/pii/S2352396424000148Lyme diseaseHost glycosylationIgG N-glycansMachine learningMultiplex lectin assayAcute immune response |
| spellingShingle | Benjamin S. Haslund-Gourley Jintong Hou Kyra Woloszczuk Elizabeth J. Horn George Dempsey Elias K. Haddad Brian Wigdahl Mary Ann Comunale Host glycosylation of immunoglobulins impairs the immune response to acute Lyme diseaseResearch in context EBioMedicine Lyme disease Host glycosylation IgG N-glycans Machine learning Multiplex lectin assay Acute immune response |
| title | Host glycosylation of immunoglobulins impairs the immune response to acute Lyme diseaseResearch in context |
| title_full | Host glycosylation of immunoglobulins impairs the immune response to acute Lyme diseaseResearch in context |
| title_fullStr | Host glycosylation of immunoglobulins impairs the immune response to acute Lyme diseaseResearch in context |
| title_full_unstemmed | Host glycosylation of immunoglobulins impairs the immune response to acute Lyme diseaseResearch in context |
| title_short | Host glycosylation of immunoglobulins impairs the immune response to acute Lyme diseaseResearch in context |
| title_sort | host glycosylation of immunoglobulins impairs the immune response to acute lyme diseaseresearch in context |
| topic | Lyme disease Host glycosylation IgG N-glycans Machine learning Multiplex lectin assay Acute immune response |
| url | http://www.sciencedirect.com/science/article/pii/S2352396424000148 |
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