TY - JOUR
T1 - Development and Validation of a Protein Array for Detection of Antibodies against the Tick-Borne Pathogen Borrelia miyamotoi
AU - Hoornstra, Dieuwertje
AU - Stukolova, Olga A.
AU - Karan, Ludmila S.
AU - Sarksyan, Denis S.
AU - Kolyasnikova, Nadezhda M.
AU - Markelov, Mikhail L.
AU - Cherkashina, Anna S.
AU - Dolgova, Anna S.
AU - Sudina, Anna E.
AU - Sokolova, Marina I.
AU - Platonov, Alexander E.
AU - Hovius, Joppe W.
N1 - Funding Information: This work was supported by Russian Science Foundation (grant 15-15-00072 to A.E.P.), the Dutch Zorg Onderzoek Nederland Medische Wetenschappen (grant 5220-03-007 to D.H. and J.W.H.), and the European Regional Development Fund and the Interreg North Sea Region Program 2014-2020 as part of the NorthTick project (grant J-No 38-2-7-19 to D.H. and J.W.H.). We declare no competing interests. Publisher Copyright: © 2022 Hoornstra et al.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - Current serological tests for the emerging tick-borne pathogen Borrelia miyamotoi lack diagnostic accuracy. To improve serodiagnosis, we investigated a protein array simultaneously screening for IgM and IgG reactivity against multiple recombinant B. miyamotoi antigens. The array included six B. miyamotoi antigens: glycerophosphodiester phosphodiesterase (GlpQ), multiple variable major proteins (Vmps), and flagellin. Sera included samples from cases of PCR-proven Borrelia miyamotoi disease (BMD), multiple potentially cross-reactive control groups (including patients with culture-proven Lyme borreliosis, confirmed Epstein-Barr virus, cytomegalovirus, or other spirochetal infections), and several healthy control groups from regions where Ixodes is endemic and regions where it is nonendemic. Based on receiver operating characteristic (ROC) analyses, the cutoff for reactivity per antigen was set at 5 mg/mL for IgM and IgG. The individual antigens demonstrated high sensitivity but relatively low specificity for both IgM and IgG. The best-performing single antigen (GlpQ) showed a sensitivity of 88.0% (95% confidence interval [CI], 78.9 to 93.5) and a specificity of 94.2% (95% CI, 92.7 to 95.6) for IgM/IgG. Applying the previous published diagnostic algorithm—defining seroreactivity as reactivity against GlpQ and any Vmp—revealed a significantly higher specificity of 98.5% (95% CI, 97.6 to 99.2) but a significantly lower sensitivity of 79.5% (95% CI, 69.3 to 87.0) for IgM/IgG compared to GlpQ alone. Therefore, we propose to define seroreactivity as reactivity against GlpQ and any Vmp or flagellin which resulted in a comparable sensitivity of 84.3% (95% CI, 74.7 to 90.8) and a significantly higher specificity of 97.9% (95% CI, 96.9 to 98.7) for IgM/IgG compared to GlpQ alone. In conclusion, we have developed and validated a novel serological tool to diagnose BMD that could be implemented in clinical practice and epidemiological studies.
AB - Current serological tests for the emerging tick-borne pathogen Borrelia miyamotoi lack diagnostic accuracy. To improve serodiagnosis, we investigated a protein array simultaneously screening for IgM and IgG reactivity against multiple recombinant B. miyamotoi antigens. The array included six B. miyamotoi antigens: glycerophosphodiester phosphodiesterase (GlpQ), multiple variable major proteins (Vmps), and flagellin. Sera included samples from cases of PCR-proven Borrelia miyamotoi disease (BMD), multiple potentially cross-reactive control groups (including patients with culture-proven Lyme borreliosis, confirmed Epstein-Barr virus, cytomegalovirus, or other spirochetal infections), and several healthy control groups from regions where Ixodes is endemic and regions where it is nonendemic. Based on receiver operating characteristic (ROC) analyses, the cutoff for reactivity per antigen was set at 5 mg/mL for IgM and IgG. The individual antigens demonstrated high sensitivity but relatively low specificity for both IgM and IgG. The best-performing single antigen (GlpQ) showed a sensitivity of 88.0% (95% confidence interval [CI], 78.9 to 93.5) and a specificity of 94.2% (95% CI, 92.7 to 95.6) for IgM/IgG. Applying the previous published diagnostic algorithm—defining seroreactivity as reactivity against GlpQ and any Vmp—revealed a significantly higher specificity of 98.5% (95% CI, 97.6 to 99.2) but a significantly lower sensitivity of 79.5% (95% CI, 69.3 to 87.0) for IgM/IgG compared to GlpQ alone. Therefore, we propose to define seroreactivity as reactivity against GlpQ and any Vmp or flagellin which resulted in a comparable sensitivity of 84.3% (95% CI, 74.7 to 90.8) and a significantly higher specificity of 97.9% (95% CI, 96.9 to 98.7) for IgM/IgG compared to GlpQ alone. In conclusion, we have developed and validated a novel serological tool to diagnose BMD that could be implemented in clinical practice and epidemiological studies.
KW - Borrelia miyamotoi
KW - Borrelia miyamotoi disease
KW - hard-tick-borne relapsing fever
KW - relapsing fever Borrelia
KW - serology
UR - http://www.scopus.com/inward/record.url?scp=85144636575&partnerID=8YFLogxK
U2 - https://doi.org/10.1128/spectrum.02036-22
DO - https://doi.org/10.1128/spectrum.02036-22
M3 - Article
C2 - 36314925
SN - 2165-0497
VL - 10
JO - Microbiology spectrum
JF - Microbiology spectrum
IS - 6
ER -