Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections

Zihui Wei; Fiona Angrisano; Emily M. Eriksson; Ramin Mazhari; Huy Van; Shuning Zheng; Rob J. Center; Irene Boo; James McMahon; Jillian Lau; Nicholas Kiernan-Walker; Shazia Ruybal-Pesántez; Ivo Mueller; Leanne J. Robinson; David A. Anderson; Heidi E. Drummer

doi:10.1111/imcb.12682

Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections

Zihui Wei, Fiona Angrisano, Emily M. Eriksson, Ramin Mazhari, Huy Van, Shuning Zheng, Rob J. Center, Irene Boo, James McMahon, Jillian Lau, Nicholas Kiernan-Walker, Shazia Ruybal-Pesántez, Ivo Mueller, Leanne J. Robinson, David A. Anderson, Heidi E. Drummer

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Abstract

Current serological tests cannot differentiate between total immunoglobulin A (IgA) and dimeric IgA (dIgA) associated with mucosal immunity. Here, we describe two new assays, dIgA-ELISA and dIgA-multiplex bead assay (MBA), that utilize the preferential binding of dIgA to a chimeric form of secretory component, allowing the differentiation between dIgA and monomeric IgA. dIgA responses elicited through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were measured in (i) a longitudinal panel, consisting of 74 samples (n = 20 individuals) from hospitalized cases of coronavirus disease 2019 (COVID-19); (ii) a longitudinal panel, consisting of 96 samples (n = 10 individuals) from individuals with mild COVID-19; (iii) a cross-sectional panel with PCR-confirmed SARS-CoV-2 infection with mild COVID-19 (n = 199) and (iv) pre–COVID-19 samples (n = 200). The dIgA-ELISA and dIgA-MBA demonstrated a specificity for dIgA of 99% and 98.5%, respectively. Analysis of dIgA responses in the longitudinal panels revealed that 70% (ELISA) and 50% (MBA) of patients elicited a dIgA response by day 20 after PCR diagnosis with a SARS-CoV-2 infection. Individuals with mild COVID-19 displayed increased levels of dIgA within the first 3 weeks after diagnosis but responses appeared to be short lived, compared with sustained IgA levels. However, in samples from hospitalized patients with COVID-19 we observed high and sustained levels of dIgA, up to 245 days after PCR diagnosis. Our results suggest that severe COVID-19 infections are associated with sustained levels of plasma dIgA compared with mild cases.

Original language	English
Pages (from-to)	857–866
Number of pages	10
Journal	Immunology and Cell Biology
Volume	101
Issue number	9
DOIs	https://doi.org/10.1111/imcb.12682
Publication status	Published - Oct 2023

Keywords

COVID-19
dIgA
mucosal immunity
serological assay

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10.1111/imcb.12682Licence: CC BY

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Wei, Z., Angrisano, F., Eriksson, E. M., Mazhari, R., Van, H., Zheng, S., Center, R. J., Boo, I., McMahon, J., Lau, J., Kiernan-Walker, N., Ruybal-Pesántez, S., Mueller, I., Robinson, L. J., Anderson, D. A., & Drummer, H. E. (2023). Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections. Immunology and Cell Biology, 101(9), 857–866. https://doi.org/10.1111/imcb.12682

@article{efea856c5eb149beaac5602ec4fa6f35,

title = "Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections",

abstract = "Current serological tests cannot differentiate between total immunoglobulin A (IgA) and dimeric IgA (dIgA) associated with mucosal immunity. Here, we describe two new assays, dIgA-ELISA and dIgA-multiplex bead assay (MBA), that utilize the preferential binding of dIgA to a chimeric form of secretory component, allowing the differentiation between dIgA and monomeric IgA. dIgA responses elicited through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were measured in (i) a longitudinal panel, consisting of 74 samples (n = 20 individuals) from hospitalized cases of coronavirus disease 2019 (COVID-19); (ii) a longitudinal panel, consisting of 96 samples (n = 10 individuals) from individuals with mild COVID-19; (iii) a cross-sectional panel with PCR-confirmed SARS-CoV-2 infection with mild COVID-19 (n = 199) and (iv) pre–COVID-19 samples (n = 200). The dIgA-ELISA and dIgA-MBA demonstrated a specificity for dIgA of 99% and 98.5%, respectively. Analysis of dIgA responses in the longitudinal panels revealed that 70% (ELISA) and 50% (MBA) of patients elicited a dIgA response by day 20 after PCR diagnosis with a SARS-CoV-2 infection. Individuals with mild COVID-19 displayed increased levels of dIgA within the first 3 weeks after diagnosis but responses appeared to be short lived, compared with sustained IgA levels. However, in samples from hospitalized patients with COVID-19 we observed high and sustained levels of dIgA, up to 245 days after PCR diagnosis. Our results suggest that severe COVID-19 infections are associated with sustained levels of plasma dIgA compared with mild cases.",

keywords = "COVID-19, dIgA, mucosal immunity, serological assay",

author = "Zihui Wei and Fiona Angrisano and Eriksson, {Emily M.} and Ramin Mazhari and Huy Van and Shuning Zheng and Center, {Rob J.} and Irene Boo and James McMahon and Jillian Lau and Nicholas Kiernan-Walker and Shazia Ruybal-Pes{\'a}ntez and Ivo Mueller and Robinson, {Leanne J.} and Anderson, {David A.} and Drummer, {Heidi E.}",

note = "Funding Information: The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute. This study was supported by the COVID‐19 Victorian Consortium grant from the Victorian Government. HV was supported by an APPRISE Research Fellowship from the National Health and Medical Research Council of Australia (NHMRC; 1116530). FA was supported by the IMPACT Philanthropy Application Program and a Burnet Institute Beever Fellowship. We thank Jessie Kingston, Sarah Hess and Stephanie Routley for technical assistance and Khayriyyah Mohd Hanafiah for technical discussions. Open access publishing facilitated by The University of Melbourne, as part of the Wiley ‐ The University of Melbourne agreement via the Council of Australian University Librarians. Publisher Copyright: {\textcopyright} 2023 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.",

year = "2023",

month = oct,

doi = "10.1111/imcb.12682",

language = "English",

volume = "101",

pages = "857–866",

journal = "Immunology and Cell Biology",

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Wei, Z, Angrisano, F, Eriksson, EM, Mazhari, R, Van, H, Zheng, S, Center, RJ, Boo, I, McMahon, J , Lau, J, Kiernan-Walker, N, Ruybal-Pesántez, S, Mueller, I, Robinson, LJ, Anderson, DA & Drummer, HE 2023, 'Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections', Immunology and Cell Biology, vol. 101, no. 9, pp. 857–866. https://doi.org/10.1111/imcb.12682

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AU - Zheng, Shuning

AU - Center, Rob J.

AU - Boo, Irene

AU - McMahon, James

AU - Lau, Jillian

AU - Kiernan-Walker, Nicholas

AU - Ruybal-Pesántez, Shazia

AU - Mueller, Ivo

AU - Robinson, Leanne J.

AU - Anderson, David A.

AU - Drummer, Heidi E.

N1 - Funding Information: The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute. This study was supported by the COVID‐19 Victorian Consortium grant from the Victorian Government. HV was supported by an APPRISE Research Fellowship from the National Health and Medical Research Council of Australia (NHMRC; 1116530). FA was supported by the IMPACT Philanthropy Application Program and a Burnet Institute Beever Fellowship. We thank Jessie Kingston, Sarah Hess and Stephanie Routley for technical assistance and Khayriyyah Mohd Hanafiah for technical discussions. Open access publishing facilitated by The University of Melbourne, as part of the Wiley ‐ The University of Melbourne agreement via the Council of Australian University Librarians. Publisher Copyright: © 2023 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.

PY - 2023/10

Y1 - 2023/10

N2 - Current serological tests cannot differentiate between total immunoglobulin A (IgA) and dimeric IgA (dIgA) associated with mucosal immunity. Here, we describe two new assays, dIgA-ELISA and dIgA-multiplex bead assay (MBA), that utilize the preferential binding of dIgA to a chimeric form of secretory component, allowing the differentiation between dIgA and monomeric IgA. dIgA responses elicited through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were measured in (i) a longitudinal panel, consisting of 74 samples (n = 20 individuals) from hospitalized cases of coronavirus disease 2019 (COVID-19); (ii) a longitudinal panel, consisting of 96 samples (n = 10 individuals) from individuals with mild COVID-19; (iii) a cross-sectional panel with PCR-confirmed SARS-CoV-2 infection with mild COVID-19 (n = 199) and (iv) pre–COVID-19 samples (n = 200). The dIgA-ELISA and dIgA-MBA demonstrated a specificity for dIgA of 99% and 98.5%, respectively. Analysis of dIgA responses in the longitudinal panels revealed that 70% (ELISA) and 50% (MBA) of patients elicited a dIgA response by day 20 after PCR diagnosis with a SARS-CoV-2 infection. Individuals with mild COVID-19 displayed increased levels of dIgA within the first 3 weeks after diagnosis but responses appeared to be short lived, compared with sustained IgA levels. However, in samples from hospitalized patients with COVID-19 we observed high and sustained levels of dIgA, up to 245 days after PCR diagnosis. Our results suggest that severe COVID-19 infections are associated with sustained levels of plasma dIgA compared with mild cases.

AB - Current serological tests cannot differentiate between total immunoglobulin A (IgA) and dimeric IgA (dIgA) associated with mucosal immunity. Here, we describe two new assays, dIgA-ELISA and dIgA-multiplex bead assay (MBA), that utilize the preferential binding of dIgA to a chimeric form of secretory component, allowing the differentiation between dIgA and monomeric IgA. dIgA responses elicited through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were measured in (i) a longitudinal panel, consisting of 74 samples (n = 20 individuals) from hospitalized cases of coronavirus disease 2019 (COVID-19); (ii) a longitudinal panel, consisting of 96 samples (n = 10 individuals) from individuals with mild COVID-19; (iii) a cross-sectional panel with PCR-confirmed SARS-CoV-2 infection with mild COVID-19 (n = 199) and (iv) pre–COVID-19 samples (n = 200). The dIgA-ELISA and dIgA-MBA demonstrated a specificity for dIgA of 99% and 98.5%, respectively. Analysis of dIgA responses in the longitudinal panels revealed that 70% (ELISA) and 50% (MBA) of patients elicited a dIgA response by day 20 after PCR diagnosis with a SARS-CoV-2 infection. Individuals with mild COVID-19 displayed increased levels of dIgA within the first 3 weeks after diagnosis but responses appeared to be short lived, compared with sustained IgA levels. However, in samples from hospitalized patients with COVID-19 we observed high and sustained levels of dIgA, up to 245 days after PCR diagnosis. Our results suggest that severe COVID-19 infections are associated with sustained levels of plasma dIgA compared with mild cases.

KW - COVID-19

KW - dIgA

KW - mucosal immunity

KW - serological assay

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JO - Immunology and Cell Biology

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ER -

Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections

Abstract

Keywords

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Australian Partnership (for) Preparedness Research on InfectiouS (disease) Emergencies (APPRISE)

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Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections

Abstract

Keywords

Access to Document

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Australian Partnership (for) Preparedness Research on InfectiouS (disease) Emergencies (APPRISE)

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