Human antibody repertoire among kidney donors with and without HIV
Xianming Zhu, William R. Morgenlander, Diane M. Brown, Yolanda Eby, Megan Morsheimer, Jonah Odim, Serena M. Bagnasco, Meenakshi M. Rana, Sander S. Florman, Rachel J. Friedman-Moraco, Peter G. Stock, Alexander J. Gilbert, Shikha Mehta, Valentina Stosor, Sapna A. Mehta, Marcus R. Pereira, Catherine B. Small, Michele I. Morris, Jonathan Hand, Saima Aslam, Ghady Haidar, Maricar Malinis, Carlos A.Q. Santos, Joanna Schaenman, David Wojciechowski, Karthik Ranganna, Emily Blumberg, Nahel Elias, Josa A. Castillo-Lugo, Emmanouil Giorgakis, Senu Apewokin, M. Kate Grabowski, Dorry L. Segev, Andrew D. Redd, Christine M. Durand, H. Benjamin Larman, Aaron A.R. Tobian, on behalf of the HOPE in Action investigators
Xianming Zhu, William R. Morgenlander, Diane M. Brown, Yolanda Eby, Megan Morsheimer, Jonah Odim, Serena M. Bagnasco, Meenakshi M. Rana, Sander S. Florman, Rachel J. Friedman-Moraco, Peter G. Stock, Alexander J. Gilbert, Shikha Mehta, Valentina Stosor, Sapna A. Mehta, Marcus R. Pereira, Catherine B. Small, Michele I. Morris, Jonathan Hand, Saima Aslam, Ghady Haidar, Maricar Malinis, Carlos A.Q. Santos, Joanna Schaenman, David Wojciechowski, Karthik Ranganna, Emily Blumberg, Nahel Elias, Josa A. Castillo-Lugo, Emmanouil Giorgakis, Senu Apewokin, M. Kate Grabowski, Dorry L. Segev, Andrew D. Redd, Christine M. Durand, H. Benjamin Larman, Aaron A.R. Tobian, on behalf of the HOPE in Action investigators
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Clinical Research and Public Health AIDS/HIV Infectious disease Public Health

Human antibody repertoire among kidney donors with and without HIV

Abstract

BACKGROUND Transplanting kidneys from donors with HIV to recipients with HIV has become standard clinical practice. However, donors with HIV may have higher prevalence of viral and bacterial infections and autoimmunity that could increase allograft rejection in recipients.METHODS We included deceased kidney donors (60 with HIV and 41 without HIV) who participated in a multicenter prospective study of HIV kidney transplantation between April 2018 and September 2021. Using phage immunoprecipitation sequencing, we compared the human antibody repertoire (allergens, autoantibodies, viruses, and bacterial toxins) between donors with and without HIV and evaluated their association with recipient allograft rejection. Moderated t tests were used to assess reactivity and a multivariate logistic regression model adjusted for donor sex and kidney donor profile index assessed the association between donor adenovirus reactivity and recipient allograft rejection.RESULTS Compared with donors without HIV, donors with HIV had lower BMI and were more likely to be African American. The median number of positive autoantibodies was marginally higher among donors with HIV (499 [IQR, 357, 579]) compared with that of donors without HIV (395 [IQR, 256, 538], P = 0.058). Donors with HIV additionally had significantly higher antibody reactivity to Epstein-Barr virus and cytomegalovirus (q < 0.05). Among all donors with and without HIV, antibodies against adenovirus were significantly associated with increased rejection among recipients, including after adjusting for false discovery (q < 0.05) and also adjusting for demographic factors using multivariable logistic regression (odds ratio = 4.97; 95% CI = 1.89–13.61).CONCLUSION The presence of antibodies against adenovirus infection in kidney donors with HIV may be associated with allograft rejection.TRIAL REGISTRATION ClinicalTrials.gov NCT03500315.FUNDING US NIH.

Authors

Xianming Zhu, William R. Morgenlander, Diane M. Brown, Yolanda Eby, Megan Morsheimer, Jonah Odim, Serena M. Bagnasco, Meenakshi M. Rana, Sander S. Florman, Rachel J. Friedman-Moraco, Peter G. Stock, Alexander J. Gilbert, Shikha Mehta, Valentina Stosor, Sapna A. Mehta, Marcus R. Pereira, Catherine B. Small, Michele I. Morris, Jonathan Hand, Saima Aslam, Ghady Haidar, Maricar Malinis, Carlos A.Q. Santos, Joanna Schaenman, David Wojciechowski, Karthik Ranganna, Emily Blumberg, Nahel Elias, Josa A. Castillo-Lugo, Emmanouil Giorgakis, Senu Apewokin, M. Kate Grabowski, Dorry L. Segev, Andrew D. Redd, Christine M. Durand, H. Benjamin Larman, Aaron A.R. Tobian, on behalf of the HOPE in Action investigators

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Figure 1

Total number of positive antibody targets among kidney transplant donors with and without HIV.

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Total number of positive antibody targets among kidney transplant donors...
Note: Hit fold change of peptides of allergens and toxins, ProMax of bacterial toxins, or VARScore of viruses >1 was considered positive. Each dot represents the total number of hits of antibody targets for a donor, stratified by their HIV status. HIV viral antibody targets were excluded from the comparison between donors with and without HIV. P values were estimated using Wilcoxon’s rank-sum tests.