TY - JOUR
T1 - Delayed kinetics of IgG, but Not IgA, antispike antibodies in transplant recipients following SARS-CoV-2 Infection
AU - Cravedi, Paolo
AU - Ahearn, Patrick
AU - Wang, Lin
AU - Yalamarti, Tanuja
AU - Hartzell, Susan
AU - Azzi, Yorg
AU - Menon, Madhav C.
AU - Jain, Aditya
AU - Billah, Marzuq
AU - Fernandez-Vina, Marcelo
AU - Gebel, Howard M.
AU - Steve Woodle, E.
AU - Haddad, Natalie S.
AU - Morrison-Porter, Andrea
AU - Eun-Hyung Lee, F.
AU - Sanz, Ignacio
AU - Akalin, Enver
AU - Girnita, Alin
AU - Maltzman, Jonathan S.
N1 - Funding Information:
E. Akalin reports consultancy agreements with CareDx and Immucor; research funding from Angion, Astellas, CareDx, and the National Institutes of Health; honoraria from CareDx and Immucor; and scientific advisor or membership with CareDx and Immucor. H.M. Gebel reports consultancy agreements with Immucor and One Lambda, a division of Thermo Fisher, and scientific advisor or membership with the Scientific Registry of Transplant Recipients. A. Girnita reports consultancy agreements with Hookipa Biotech GmbH (Vienna, Austria), INTEGRIS Baptist Medical Center (Oklahoma City, OK), and Kezar Life Science (San Francisco, CA). F.E.-H. Lee is the founder of Micro-plex, Inc.; receives grants from BMGF and Genentech; is a member of the scientific advisory board of Be Bio Pharma; has received research funding via grants from BMGF and Genentech; has received honoraria from Be Bio Pharma; and receives license royalties from BLI, Inc. J.S. Maltzman has received honoraria from FOCIS and One Lambda, Inc./Thermo Fisher; has received research funding from One Lambda/Thermo Fisher; is a member of the American Society of Nephrology (ASN) Kidney Week Education Committee (ended November 2020); was on the board of directors of the American Society of Transplantation (AST; ended June 2021); was part of the AST Research Network (ended June 2021); is Secretary/Treasurer of the Federation of Clinical Immunology Societies; is on the Transplantation Science Committee of the Transplantation Society; is a member of the ASN Qihan Biotech scientific advisory board; and has a family member who is employed by and has an equity interest in Genentech/Roche. M. C. Menon reports ownership interest in Renalytix AI and scientific advisor or membership with the JASN editorial board as a former editorial fellow, the Journal of Clinical Medicine editorial board, and Clinical Transplantation as an associate editor. I. Sanz reports consultancy agreements with BMS, Cel-gene, GSK, Janssen, Kyverna, and Visterra; ownership interest in Kyverna; research funding from Exagen and GSK; honoraria from BMS/Celgene, GSK, Janssen, and Visterra; and scientific advisor or membership with Kyverna. E.S. Woodle reports consultancy agreements with Novartis and Sanofi; research funding from Amgen, Bristol Myers Squibb, Novartis, and Veloxis; honoraria from Novartis and Sanofi; and speakers bureau with Sanofi. All remaining authors have nothing to disclose.
Funding Information:
This work was funded by National Institutes of Health, National Institute of Allergy and Infectious Diseases grants 3U01AI063594-17S1 (to P. Cravedi and M.C. Menon) and P01AI125180-05S1 (to F.E.-H. Lee and I. Sanz) and Thermo Fisher Scientific/One Lambda, Inc. (to J.S. Maltzman).
Publisher Copyright:
© 2021 American Society of Nephrology. All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - Background Kidney transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies against the virus are thought to offer protection, but a thorough characterization of anti SARSCoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. Methods We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early ( 14 days) or late (>14 days) time points after documented SARS-CoV-2 infection. Using a validated semiquantitative Luminex-based multiplex assay, we determined the abundances of IgM, IgG, IgG1 4, and IgA antibodies against five distinct viral epitopes. Results Kidney transplant recipients showed lower levels of total IgG antitrimeric spike (S), S1, S2, and receptor binding domain (RBD) but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG antispike protein epitopes were also lower than in immunocompetent controls. Anti SARS-CoV-2 antibodies were predominantly IgG1 and IgG3, with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG antispike, S1, S2, RBD, and NC did not significantly differ between cohorts. There was no significant difference in the kinetics of either IgM or IgA antispike, S1, RBD, or S2 on the basis of timing after diagnosis or transplant status. Conclusions Kidney transplant recipients mount early anti SARS-CoV-2 IgA and IgM responses, whereas IgG responses are delayed compared with immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19.
AB - Background Kidney transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies against the virus are thought to offer protection, but a thorough characterization of anti SARSCoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. Methods We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early ( 14 days) or late (>14 days) time points after documented SARS-CoV-2 infection. Using a validated semiquantitative Luminex-based multiplex assay, we determined the abundances of IgM, IgG, IgG1 4, and IgA antibodies against five distinct viral epitopes. Results Kidney transplant recipients showed lower levels of total IgG antitrimeric spike (S), S1, S2, and receptor binding domain (RBD) but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG antispike protein epitopes were also lower than in immunocompetent controls. Anti SARS-CoV-2 antibodies were predominantly IgG1 and IgG3, with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG antispike, S1, S2, RBD, and NC did not significantly differ between cohorts. There was no significant difference in the kinetics of either IgM or IgA antispike, S1, RBD, or S2 on the basis of timing after diagnosis or transplant status. Conclusions Kidney transplant recipients mount early anti SARS-CoV-2 IgA and IgM responses, whereas IgG responses are delayed compared with immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19.
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U2 - 10.1681/ASN.2021040573
DO - 10.1681/ASN.2021040573
M3 - Article
C2 - 34599041
AN - SCOPUS:85120677086
SN - 1046-6673
VL - 32
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
IS - 12
ER -