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Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples

Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence i...

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Autores principales: Suchard, Melinda S., Martinson, Neil, Malfeld, Susan, de Assis Rosa, Debbie, Mackelprang, Romel D., Lingappa, Jairam, Hou, Xuanlin, Rees, Helen, Delany-Moretlwe, Sinead, Goldfein, Hadassa, Ranchod, Heena, Coetzee, David, Otwombe, Kennedy, Morris, Lynn, Tiemessen, Caroline T., Savulescu, Dana M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987441/
https://www.ncbi.nlm.nih.gov/pubmed/35401581
http://dx.doi.org/10.3389/fimmu.2022.813412
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author Suchard, Melinda S.
Martinson, Neil
Malfeld, Susan
de Assis Rosa, Debbie
Mackelprang, Romel D.
Lingappa, Jairam
Hou, Xuanlin
Rees, Helen
Delany-Moretlwe, Sinead
Goldfein, Hadassa
Ranchod, Heena
Coetzee, David
Otwombe, Kennedy
Morris, Lynn
Tiemessen, Caroline T.
Savulescu, Dana M.
author_facet Suchard, Melinda S.
Martinson, Neil
Malfeld, Susan
de Assis Rosa, Debbie
Mackelprang, Romel D.
Lingappa, Jairam
Hou, Xuanlin
Rees, Helen
Delany-Moretlwe, Sinead
Goldfein, Hadassa
Ranchod, Heena
Coetzee, David
Otwombe, Kennedy
Morris, Lynn
Tiemessen, Caroline T.
Savulescu, Dana M.
author_sort Suchard, Melinda S.
collection PubMed
description Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence includes macaque studies which suggest that xenoimmunization with HLA antigens may protect against simian immunodeficiency virus infection. Since HIV gp120 shows homology with class 2 HLA, including shared affinity for binding to CD4, class 2 HLA antibodies may influence HIV acquisition via binding to gp120 on the viral envelope. We conducted a nested case-control study on HIV serodiscordant couples, comparing the frequency of HLA antibodies among highly exposed persistently seronegative controls with those who went on to acquire HIV (HIV-seroconverters). We first performed low resolution HLA typing on 143 individuals who were HIV-infected at enrollment (index partners) and their corresponding sexual partners (115 highly exposed persistently seronegative individuals and 28 HIV-seroconverters). We then measured HLA class 1 and 2 antibodies in the highly exposed persistently seronegative individuals and HIV-seroconverters at early and late timepoints. We analyzed whether such antibodies were directed at HLA specificities of their HIV-infected index partners, and whether autoantibodies or complement-fixing class 2 HLA antibodies were present. Seventy-nine percent of highly exposed persistently seronegative individuals had HLA antibodies; 56% against class 1 and 50% against class 2 alleles. Half of the group of highly exposed persistently seronegative individuals, prior to seroconversion, expressed class 2 HLA antibodies, compared with only 29% of controls (p=0.05). HIV infection was a sensitizing event leading to de novo development of antibodies against HLA-A and HLA-B loci, but not against class 2 loci. HLA autoantibodies were present in 27% of highly exposed persistently seronegative individuals. Complement-fixing class 2 HLA antibodies did not differ significantly between highly exposed persistently seronegative individuals and seroconverters. In multivariable regression, presence of class 2 HLA antibodies at early timepoints was associated with reduced odds of HIV acquisition (odds ratio 0.330, confidence interval 0.112-0.976, p=0.045). These epidemiological data suggest that pre-existing class 2 HLA antibodies were associated with reduced odds of HIV acquisition.
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spelling pubmed-89874412022-04-08 Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples Suchard, Melinda S. Martinson, Neil Malfeld, Susan de Assis Rosa, Debbie Mackelprang, Romel D. Lingappa, Jairam Hou, Xuanlin Rees, Helen Delany-Moretlwe, Sinead Goldfein, Hadassa Ranchod, Heena Coetzee, David Otwombe, Kennedy Morris, Lynn Tiemessen, Caroline T. Savulescu, Dana M. Front Immunol Immunology Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence includes macaque studies which suggest that xenoimmunization with HLA antigens may protect against simian immunodeficiency virus infection. Since HIV gp120 shows homology with class 2 HLA, including shared affinity for binding to CD4, class 2 HLA antibodies may influence HIV acquisition via binding to gp120 on the viral envelope. We conducted a nested case-control study on HIV serodiscordant couples, comparing the frequency of HLA antibodies among highly exposed persistently seronegative controls with those who went on to acquire HIV (HIV-seroconverters). We first performed low resolution HLA typing on 143 individuals who were HIV-infected at enrollment (index partners) and their corresponding sexual partners (115 highly exposed persistently seronegative individuals and 28 HIV-seroconverters). We then measured HLA class 1 and 2 antibodies in the highly exposed persistently seronegative individuals and HIV-seroconverters at early and late timepoints. We analyzed whether such antibodies were directed at HLA specificities of their HIV-infected index partners, and whether autoantibodies or complement-fixing class 2 HLA antibodies were present. Seventy-nine percent of highly exposed persistently seronegative individuals had HLA antibodies; 56% against class 1 and 50% against class 2 alleles. Half of the group of highly exposed persistently seronegative individuals, prior to seroconversion, expressed class 2 HLA antibodies, compared with only 29% of controls (p=0.05). HIV infection was a sensitizing event leading to de novo development of antibodies against HLA-A and HLA-B loci, but not against class 2 loci. HLA autoantibodies were present in 27% of highly exposed persistently seronegative individuals. Complement-fixing class 2 HLA antibodies did not differ significantly between highly exposed persistently seronegative individuals and seroconverters. In multivariable regression, presence of class 2 HLA antibodies at early timepoints was associated with reduced odds of HIV acquisition (odds ratio 0.330, confidence interval 0.112-0.976, p=0.045). These epidemiological data suggest that pre-existing class 2 HLA antibodies were associated with reduced odds of HIV acquisition. Frontiers Media S.A. 2022-03-24 /pmc/articles/PMC8987441/ /pubmed/35401581 http://dx.doi.org/10.3389/fimmu.2022.813412 Text en Copyright © 2022 Suchard, Martinson, Malfeld, de Assis Rosa, Mackelprang, Lingappa, Hou, Rees, Delany-Moretlwe, Goldfein, Ranchod, Coetzee, Otwombe, Morris, Tiemessen and Savulescu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Suchard, Melinda S.
Martinson, Neil
Malfeld, Susan
de Assis Rosa, Debbie
Mackelprang, Romel D.
Lingappa, Jairam
Hou, Xuanlin
Rees, Helen
Delany-Moretlwe, Sinead
Goldfein, Hadassa
Ranchod, Heena
Coetzee, David
Otwombe, Kennedy
Morris, Lynn
Tiemessen, Caroline T.
Savulescu, Dana M.
Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples
title Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples
title_full Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples
title_fullStr Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples
title_full_unstemmed Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples
title_short Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples
title_sort alloimmunity to class 2 human leucocyte antigens may reduce hiv-1 acquisition – a nested case-control study in hiv-1 serodiscordant couples
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987441/
https://www.ncbi.nlm.nih.gov/pubmed/35401581
http://dx.doi.org/10.3389/fimmu.2022.813412
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