TY - JOUR
T1 - Analysis of Cross-sectional and Longitudinal HLA and Anti-viral Responses after COVID Infection in Renal Allograft Recipients
T2 - Differences and Correlates
AU - Girnita, Alin L.
AU - Wang, Lin
AU - Colovai, Adriana I.
AU - Ahearn, Patrick
AU - Azzi, Yorg
AU - Menon, Madhav C.
AU - Fernandez-Vina, Marcelo
AU - Gebel, Howard M.
AU - Steve Woodle, E.
AU - Cravedi, Paolo
AU - Maltzman, Jonathan S.
AU - Akalin, Enver
N1 - Funding Information:
J.S.M. has received honoraria from One Lambda, Inc./ThermoFisher, serves on the Qihan Biotech SAB, and has a family member who is employed by and has an equity interest in Genentech/Roche. E.A. has received research grant support from the National Institutes of Health (NIH), CareDx, Immucor and Advisory Board at CareDx, Immucor, Exosome, and Takeda. M.C.M. and P.C. have received research grant support from NIH National Institute of Allergy and Infectious Diseases (NIAID), ancillary mechanistic grant associated with Grant 3U01AI063594-17S1. P.A. has received research grant support from NIH NIAID, R25 AI147369. The other authors declare no conflicts of interest.
Publisher Copyright:
© 2022 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Background. Characterization of anti-HLA versus anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) immune globulin isotypes in organ transplant recipients after coronavirus disease 2019 (COVID-19) infection has not been reported. We aimed to determine changes in anti-HLA antibodies in renal transplant patients with COVID-19 and compare the immunoglobulin and epitope-binding pattern versus anti-SARS-CoV-2 antibodies. Methods. This is a cross-sectional study of 46 kidney transplant recipients including 21 with longitudinal sampling. Using a semi-quantitative multiplex assay, we determined immunoglobulin (Ig) M, IgA, IgG, and IgG1-2-3-4 antibodies against Class I and Class II HLA, and 5 SARS-CoV-2 epitopes including the nucleocapsid protein and multiple regions of the spike protein. Results. Fourteen of 46 (30%) patients had donor-specific anti-HLA antibodies (donor-specific antibody [DSA]), 12 (26%) had non-DSA anti-HLA antibodies and 45 (98%) had anti-SARS-CoV-2 antibodies. Most DSAs targeted HLA-DQ (71%), with a dominant IgG isotype and IgG1 subtype prevalence (93%), and/or IgG3 (64%), followed by IgG2 (36%). Comparatively, there was a higher prevalence of IgA (85% versus 14%, P = 0.0001) and IgM (87%, versus 36%, P = 0.001) in the anti-SARS-CoV-2 antibody profile, when compared to DSAs, respectively. Anti-SARS-CoV-2 antibody profile was characterized by increased prevalence of IgM and IgA, when compared to DSAs. The median calculated panel reactive antibody before COVID-19 diagnosis (24%) tended to decrease after COVID-19 diagnosis (10%) but it was not statistically significant (P = 0.1). Conclusions. Anti-HLA antibody strength and calculated panel reactive antibody in kidney transplant recipients after COVID-19 do not significantly increase after infection. Although the IgG isotype was the dominant form in both HLA and SARS-CoV-2 antigens, the alloimmune response had a low IgA pattern, whereas anti-SARS-CoV-2 antibodies were high IgA/IgM.
AB - Background. Characterization of anti-HLA versus anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) immune globulin isotypes in organ transplant recipients after coronavirus disease 2019 (COVID-19) infection has not been reported. We aimed to determine changes in anti-HLA antibodies in renal transplant patients with COVID-19 and compare the immunoglobulin and epitope-binding pattern versus anti-SARS-CoV-2 antibodies. Methods. This is a cross-sectional study of 46 kidney transplant recipients including 21 with longitudinal sampling. Using a semi-quantitative multiplex assay, we determined immunoglobulin (Ig) M, IgA, IgG, and IgG1-2-3-4 antibodies against Class I and Class II HLA, and 5 SARS-CoV-2 epitopes including the nucleocapsid protein and multiple regions of the spike protein. Results. Fourteen of 46 (30%) patients had donor-specific anti-HLA antibodies (donor-specific antibody [DSA]), 12 (26%) had non-DSA anti-HLA antibodies and 45 (98%) had anti-SARS-CoV-2 antibodies. Most DSAs targeted HLA-DQ (71%), with a dominant IgG isotype and IgG1 subtype prevalence (93%), and/or IgG3 (64%), followed by IgG2 (36%). Comparatively, there was a higher prevalence of IgA (85% versus 14%, P = 0.0001) and IgM (87%, versus 36%, P = 0.001) in the anti-SARS-CoV-2 antibody profile, when compared to DSAs, respectively. Anti-SARS-CoV-2 antibody profile was characterized by increased prevalence of IgM and IgA, when compared to DSAs. The median calculated panel reactive antibody before COVID-19 diagnosis (24%) tended to decrease after COVID-19 diagnosis (10%) but it was not statistically significant (P = 0.1). Conclusions. Anti-HLA antibody strength and calculated panel reactive antibody in kidney transplant recipients after COVID-19 do not significantly increase after infection. Although the IgG isotype was the dominant form in both HLA and SARS-CoV-2 antigens, the alloimmune response had a low IgA pattern, whereas anti-SARS-CoV-2 antibodies were high IgA/IgM.
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U2 - 10.1097/TP.0000000000004277
DO - 10.1097/TP.0000000000004277
M3 - Article
C2 - 36070571
AN - SCOPUS:85139376478
SN - 0041-1337
VL - 106
SP - 2085
EP - 2091
JO - Transplantation
JF - Transplantation
IS - 10
ER -