Rapid single-tier serodiagnosis of Lyme disease

• Published in: Nature communications Vol. 15; no. 1; pp. 7124 - 13
• Main Authors: Ghosh, Rajesh, Joung, Hyou-Arm, Goncharov, Artem, Palanisamy, Barath, Ngo, Kevin, Pejcinovic, Katarina, Krockenberger, Nicole, Horn, Elizabeth J., Garner, Omai B., Ghazal, Ezdehar, O’Kula, Andrew, Arnaboldi, Paul M., Dattwyler, Raymond J., Ozcan, Aydogan, Di Carlo, Dino
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/62; 49/75; 631/1647/277; 631/250/2152/2153/1291; 631/250/2499; 639/166/985; 692/699/255/1318; 82/1; 9/10; 96/63; Antibodies; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antigens; Antigens, Bacterial - immunology; Borrelia burgdorferi - immunology; Diagnosis; Diagnostic systems; Epitopes; Epitopes - immunology; Humanities and Social Sciences; Humans; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin M; Immunoglobulin M - blood; Immunoglobulin M - immunology; Learning algorithms; Lyme disease; Lyme Disease - blood; Lyme Disease - diagnosis; Lyme Disease - immunology; Lyme Disease - microbiology; Machine Learning; multidisciplinary; Peptides; Point-of-Care Systems; Point-of-Care Testing; Science; Science (multidisciplinary); Sensitivity; Sensitivity analysis; Sensitivity and Specificity; Serologic Tests - methods; Synthetic peptides; Vector-borne diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-51067-5

Point-of-care serological and direct antigen testing offers actionable insights for diagnosing challenging illnesses, empowering distributed health systems. Here, we report a POC-compatible serologic test for Lyme disease (LD), leveraging synthetic peptides specific to LD antibodies and a paper-based platform for rapid, and cost-effective diagnosis. Antigenic epitopes conserved across Borrelia burgdorferi genospecies, targeted by IgG and IgM antibodies, are selected to develop a multiplexed panel for detection of LD antibodies from patient sera. Multiple peptide epitopes, when combined synergistically with a machine learning-based diagnostic model achieve high sensitivity without sacrificing specificity. Blinded validation with 15 LD-positive and 15 negative samples shows 95.5% sensitivity and 100% specificity. Blind testing with the CDC’s LD repository samples confirms the test accuracy, matching lab-based two-tier results, correctly differentiating between LD and look-alike diseases. This LD diagnostic test could potentially replace the cumbersome two-tier testing, improving diagnosis and enabling earlier treatment while facilitating immune monitoring and surveillance. Lyme disease is the leading vector-borne disease in North America and Europe, but it lacks single tests for early diagnosis. Here, authors develop a rapid and low-cost serologic test using synthetic peptides, a paper-based assay, and machine learning.