Rapid single-tier serodiagnosis of Lyme disease.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
20 Aug 2024
Historique:
received: 21 07 2023
accepted: 29 07 2024
medline: 21 8 2024
pubmed: 21 8 2024
entrez: 20 8 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 39164226
doi: 10.1038/s41467-024-51067-5
pii: 10.1038/s41467-024-51067-5
doi:

Substances chimiques

Antibodies, Bacterial 0
Immunoglobulin M 0
Immunoglobulin G 0
Antigens, Bacterial 0
Epitopes 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7124

Subventions

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R44AI150060
Organisme : National Science Foundation (NSF)
ID : 1648451

Informations de copyright

© 2024. The Author(s).

Références

Chen, H., Liu, K., Li, Z. & Wang, P. Point of care testing for infectious diseases. Clin. Chim. Acta 493, 138–147 (2019).
doi: 10.1016/j.cca.2019.03.008 pubmed: 30853460 pmcid: 6462423
Mercer, T. R. & Salit, M. Testing at scale during the COVID-19 pandemic. Nat. Rev. Genet. 22, 415–426 (2021).
doi: 10.1038/s41576-021-00360-w pubmed: 33948037 pmcid: 8094986
Valera, E. et al. COVID-19 point-of-care diagnostics: present and future. ACS Nano 15, 7899–7906 (2021).
doi: 10.1021/acsnano.1c02981 pubmed: 33984237
Song, Q. et al. Point-of-care testing detection methods for COVID-19. Lab. Chip 21, 1634–1660 (2021).
doi: 10.1039/D0LC01156H pubmed: 33705507
Steere, A. C. Lyme disease. N. Engl. J. Med. 345, 115–125 (2001).
doi: 10.1056/NEJM200107123450207 pubmed: 11450660
Stanek, G., Wormser, G. P., Gray, J. & Strle, F. Lyme borreliosis. Lancet 379, 461–473 (2012).
doi: 10.1016/S0140-6736(11)60103-7 pubmed: 21903253
Brownstein, J. S., Holford, T. R. & Fish, D. Effect of climate change on Lyme disease risk in North America. EcoHealth 2, 38–46 (2005).
doi: 10.1007/s10393-004-0139-x pubmed: 19008966 pmcid: 2582486
Steere, A. C. & Sikand, V. K. The presenting manifestations of Lyme disease and the outcomes of treatment. N. Engl. J. Med. 348, 2472–2474 (2003).
doi: 10.1056/NEJM200306123482423 pubmed: 12802042
Lantos, P. M. et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis, and treatment of Lyme disease. Arthritis Care Res. 73, 1–9 (2021).
doi: 10.1002/acr.24495
Wormser, G. P. et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and Babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin. Infect. Dis. 43, 1089–1134 (2006).
doi: 10.1086/508667 pubmed: 17029130
Hinckley, A. F. et al. Lyme disease testing by large commercial laboratories in the United States. Clin. Infect. Dis. 59, 676–681 (2014).
doi: 10.1093/cid/ciu397 pubmed: 24879782
Branda, J. A. & Steere, A. C. Laboratory diagnosis of Lyme borreliosis. Clin. Microbiol. Rev. 34, e00018–e00019 (2021).
doi: 10.1128/CMR.00018-19 pubmed: 33504503 pmcid: 7849240
Moore, A., Nelson, C., Molins, C., Mead, P. & Schriefer, M. Current guidelines, common clinical pitfalls, and future directions for laboratory diagnosis of Lyme disease, United States. Emerg. Infect. Dis. 22, 1169–1177 (2016).
doi: 10.3201/eid2207.151694 pubmed: 27314832 pmcid: 4918152
Branda, J. A. et al. Advances in serodiagnostic testing for Lyme disease are at hand. Clin. Infect. Dis. 66, 1133–1139 (2018).
doi: 10.1093/cid/cix943 pubmed: 29228208
Schiffman, E. K. et al. Underreporting of Lyme and other tick-borne diseases in residents of a high-incidence county, Minnesota, 2009. Zoonoses Public Health 65, 230–237 (2018).
doi: 10.1111/zph.12291 pubmed: 27390047
Wormser, G. P. et al. Comparative cost-effectiveness of two-tiered testing strategies for serodiagnosis of Lyme disease with noncutaneous manifestations. J. Clin. Microbiol. 51, 4045–4049 (2013).
doi: 10.1128/JCM.01853-13 pubmed: 24068010 pmcid: 3838032
Wormser, G. P. et al. A limitation of 2-stage serological testing for Lyme disease: enzyme immunoassay and immunoblot assay are not independent tests. Clin. Infect. Dis. 30, 545–548 (2000).
doi: 10.1086/313688 pubmed: 10722442
Lahey, L. J. et al. Development of a multiantigen panel for improved detection of Borrelia burgdorferi infection in early Lyme disease. J. Clin. Microbiol. 53, 3834–3841 (2015).
doi: 10.1128/JCM.02111-15 pubmed: 26447113 pmcid: 4652118
Joung, H.-A. et al. Point-of-care serodiagnostic test for early-stage Lyme disease using a multiplexed paper-based immunoassay and machine learning. ACS Nano 14, 229–240 (2020).
doi: 10.1021/acsnano.9b08151 pubmed: 31849225
Embers, M. E., Hasenkampf, N. R., Jacobs, M. B. & Philipp, M. T. Dynamic longitudinal antibody responses during Borrelia burgdorferi infection and antibiotic treatment of Rhesus macaques. Clin. Vaccin. Immunol. 19, 1218–1226 (2012).
doi: 10.1128/CVI.00228-12
Liang, L. et al. Rapid clearance of Borrelia burgdorferi from the blood circulation. Parasit. Vectors 13, 191 (2020).
doi: 10.1186/s13071-020-04060-y pubmed: 32312278 pmcid: 7171858
Ballard, Z. S. et al. Deep learning-enabled point-of-care sensing using multiplexed paper-based sensors. Npj Digit. Med. 3, 1–8 (2020).
doi: 10.1038/s41746-020-0274-y
Brown, C. et al. Automated, cost-effective optical system for accelerated antimicrobial susceptibility testing (AST) using deep learning. ACS Photonics 7, 2527–2538 (2020).
doi: 10.1021/acsphotonics.0c00841
Goncharov, A. et al. Deep learning-enabled multiplexed point-of-care sensor using a paper-based fluorescence vertical flow assay. Small 19, 2300617 (2023).
doi: 10.1002/smll.202300617
Arnaboldi, P. M., Katseff, A. S., Sambir, M. & Dattwyler, R. J. Linear peptide epitopes derived from ErpP, p35, and FlaB in the serodiagnosis of Lyme disease. Pathogens 11, 944 (2022).
doi: 10.3390/pathogens11080944 pubmed: 36015064 pmcid: 9414810
Arnaboldi, P. M. et al. Outer surface protein C peptide derived from Borrelia burgdorferi sensu stricto as a target for serodiagnosis of early Lyme disease. Clin. Vaccin. Immunol. 20, 474–481 (2013).
doi: 10.1128/CVI.00608-12
Arnaboldi, P. M., Sambir, M. & Dattwyler, R. J. Decorin binding proteins A and B in the serodiagnosis of Lyme disease in North America. Clin. Vaccin. Immunol. 21, 1426–1436 (2014).
doi: 10.1128/CVI.00383-14
Signorino, G., Arnaboldi, P. M., Petzke, M. M. & Dattwyler, R. J. Identification of OppA2 linear epitopes as serodiagnostic markers for Lyme disease. Clin. Vaccin. Immunol. 21, 704–711 (2014).
doi: 10.1128/CVI.00792-13
Toumanios, C., Prisco, L., Dattwyler, R. J. & Arnaboldi, P. M. Linear B cell epitopes derived from the multifunctional surface lipoprotein BBK32 as targets for the serodiagnosis of Lyme disease. mSphere 4, e00111–e00119 (2019).
doi: 10.1128/mSphere.00111-19 pubmed: 31043513 pmcid: 6495335
Joung, H.-A. et al. Paper-based multiplexed vertical flow assay for point-of-care testing. Lab. Chip 19, 1027–1034 (2019).
doi: 10.1039/C9LC00011A pubmed: 30729974
Horn, E. J. et al. The Lyme disease biobank: characterization of 550 patient and control samples from the East Coast and Upper Midwest of the United States. J. Clin. Microbiol. 58, e00032–20 (2020).
doi: 10.1128/JCM.00032-20 pubmed: 32102853 pmcid: 7269379
Molins, C. R. et al. Collection and characterization of samples for establishment of a serum repository for lyme disease diagnostic test development and evaluation. J. Clin. Microbiol. 52, 3755–3762 (2014).
doi: 10.1128/JCM.01409-14 pubmed: 25122862 pmcid: 4187768

Auteurs

Rajesh Ghosh (R)

Bioengineering Department, University of California, Los Angeles, CA, 90095, USA.

Hyou-Arm Joung (HA)

Electrical & Computer Engineering Department, University of California, Los Angeles, CA, 90095, USA.
California NanoSystems Institute (CNSI), University of California, Los Angeles, CA, 90095, USA.

Artem Goncharov (A)

Electrical & Computer Engineering Department, University of California, Los Angeles, CA, 90095, USA.
California NanoSystems Institute (CNSI), University of California, Los Angeles, CA, 90095, USA.

Barath Palanisamy (B)

Bioengineering Department, University of California, Los Angeles, CA, 90095, USA.

Kevin Ngo (K)

Bioengineering Department, University of California, Los Angeles, CA, 90095, USA.

Katarina Pejcinovic (K)

Bioengineering Department, University of California, Los Angeles, CA, 90095, USA.

Nicole Krockenberger (N)

Bioengineering Department, University of California, Los Angeles, CA, 90095, USA.

Elizabeth J Horn (EJ)

Lyme Disease Biobank, Portland, Oregon, OR, 97221, USA.

Omai B Garner (OB)

Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, 90095, USA.

Ezdehar Ghazal (E)

Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, NY, 10595, USA.

Andrew O'Kula (A)

Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, NY, 10595, USA.

Paul M Arnaboldi (PM)

Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, NY, 10595, USA.
Biopeptides, Corp, Ridgefield, CT, 06877, USA.

Raymond J Dattwyler (RJ)

Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, NY, 10595, USA.
Biopeptides, Corp, Ridgefield, CT, 06877, USA.

Aydogan Ozcan (A)

Bioengineering Department, University of California, Los Angeles, CA, 90095, USA. ozcan@ucla.edu.
Electrical & Computer Engineering Department, University of California, Los Angeles, CA, 90095, USA. ozcan@ucla.edu.
California NanoSystems Institute (CNSI), University of California, Los Angeles, CA, 90095, USA. ozcan@ucla.edu.
Department of Surgery, University of California, Los Angeles, CA, 90095, USA. ozcan@ucla.edu.

Dino Di Carlo (D)

Bioengineering Department, University of California, Los Angeles, CA, 90095, USA. dicarlo@ucla.edu.
California NanoSystems Institute (CNSI), University of California, Los Angeles, CA, 90095, USA. dicarlo@ucla.edu.
Department of Mechanical Engineering, University of California, Los Angeles, CA, 90095, USA. dicarlo@ucla.edu.

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Classifications MeSH