Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients
IntroductionImmunity to Human leukocyte antigen (HLA) cannot explain all cases of ABMR, nor the differences observed in the outcome of kidney recipients with circulating DSAs endowed with similar biologic characteristics. Thus, increasing attention has recently been focused on the role of immunity t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1035400/full |
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| author | Patrizia Comoli Michela Cioni Bryan Ray Augusto Tagliamacco Annalisa Innocente Gianluca Caridi Maurizio Bruschi Jayasree Hariharan Iris Fontana Antonella Trivelli Alberto Magnasco Angela Nocco Catherine Klersy Stella Muscianisi Gian Marco Ghiggeri Massimo Cardillo Enrico Verrina Arcangelo Nocera Fabrizio Ginevri |
| author_facet | Patrizia Comoli Michela Cioni Bryan Ray Augusto Tagliamacco Annalisa Innocente Gianluca Caridi Maurizio Bruschi Jayasree Hariharan Iris Fontana Antonella Trivelli Alberto Magnasco Angela Nocco Catherine Klersy Stella Muscianisi Gian Marco Ghiggeri Massimo Cardillo Enrico Verrina Arcangelo Nocera Fabrizio Ginevri |
| author_sort | Patrizia Comoli |
| collection | DOAJ |
| description | IntroductionImmunity to Human leukocyte antigen (HLA) cannot explain all cases of ABMR, nor the differences observed in the outcome of kidney recipients with circulating DSAs endowed with similar biologic characteristics. Thus, increasing attention has recently been focused on the role of immunity to non-HLA antigenic targets.MethodsWe analyzed humoral auto- and alloimmune responses to the non-HLA antigen glutathione S-transferase theta 1 (GSTT1), along with development of de novo (dn)HLA-DSAs, in a cohort of 146 pediatric non-sensitized recipients of first kidney allograft, to analyze its role in ABMR and graft loss. A multiplex bead assay was employed to assess GSTT1 antibodies (Abs).ResultsWe observed development of GSTT1 Abs in 71 recipients after transplantation, 16 with MFI > 8031 (4th quartile: Q4 group). In univariate analyses, we found an association between Q4-GSTT1Abs and ABMR and graft loss, suggesting a potential role in inducing graft damage, as GSTT1 Abs were identified within ABMR biopsies of patients with graft function deterioration in the absence of concomitant intragraft HLA-DSAs. HLA-DSAs and GSTT1 Abs were independent predictors of graft loss in our cohort. As GSTT1 Ab development preceded or coincided with the appearance of dnHLA-DSAs, we tested and found that a model with the two combined parameters proved more fit to classify patients at risk of graft loss.DiscussionOur observations on the harmful effects of GSTT1Abs, alone or in combination with HLA-DSAs, add to the evidence pointing to a negative role of allo- and auto-non-HLA Abs on kidney graft outcome. |
| first_indexed | 2024-04-13T13:12:48Z |
| format | Article |
| id | doaj.art-610998b206cb4b1aa065e24f5939d069 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-13T13:12:48Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-610998b206cb4b1aa065e24f5939d0692022-12-22T02:45:33ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-11-01910.3389/fmed.2022.10354001035400Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipientsPatrizia Comoli0Michela Cioni1Bryan Ray2Augusto Tagliamacco3Annalisa Innocente4Gianluca Caridi5Maurizio Bruschi6Jayasree Hariharan7Iris Fontana8Antonella Trivelli9Alberto Magnasco10Angela Nocco11Catherine Klersy12Stella Muscianisi13Gian Marco Ghiggeri14Massimo Cardillo15Enrico Verrina16Arcangelo Nocera17Fabrizio Ginevri18UOSD Cell Factory and UOC Pediatric Hematology/Oncology, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyImmucor Inc., Norcross, GA, United StatesTransplantation Immunology, Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan, ItalyTransplantation Immunology, Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyImmucor Inc., Norcross, GA, United StatesVascular and Endovascular Unit and Kidney Transplant Surgery Unit, IRCCS San Martino University Hospital IST, University of Genoa, Genoa, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyTransplantation Immunology, Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan, ItalyBiometry and Statistics Service, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, ItalyUOSD Cell Factory and UOC Pediatric Hematology/Oncology, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyItalian National Transplant Centre, Italian National Institute of Health (ISS), Rome, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyNephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, ItalyIntroductionImmunity to Human leukocyte antigen (HLA) cannot explain all cases of ABMR, nor the differences observed in the outcome of kidney recipients with circulating DSAs endowed with similar biologic characteristics. Thus, increasing attention has recently been focused on the role of immunity to non-HLA antigenic targets.MethodsWe analyzed humoral auto- and alloimmune responses to the non-HLA antigen glutathione S-transferase theta 1 (GSTT1), along with development of de novo (dn)HLA-DSAs, in a cohort of 146 pediatric non-sensitized recipients of first kidney allograft, to analyze its role in ABMR and graft loss. A multiplex bead assay was employed to assess GSTT1 antibodies (Abs).ResultsWe observed development of GSTT1 Abs in 71 recipients after transplantation, 16 with MFI > 8031 (4th quartile: Q4 group). In univariate analyses, we found an association between Q4-GSTT1Abs and ABMR and graft loss, suggesting a potential role in inducing graft damage, as GSTT1 Abs were identified within ABMR biopsies of patients with graft function deterioration in the absence of concomitant intragraft HLA-DSAs. HLA-DSAs and GSTT1 Abs were independent predictors of graft loss in our cohort. As GSTT1 Ab development preceded or coincided with the appearance of dnHLA-DSAs, we tested and found that a model with the two combined parameters proved more fit to classify patients at risk of graft loss.DiscussionOur observations on the harmful effects of GSTT1Abs, alone or in combination with HLA-DSAs, add to the evidence pointing to a negative role of allo- and auto-non-HLA Abs on kidney graft outcome.https://www.frontiersin.org/articles/10.3389/fmed.2022.1035400/fullkidney transplantationnon-HLA antigensautoantibodiesalloantibodiesantibody mediated rejectionallograft loss |
| spellingShingle | Patrizia Comoli Michela Cioni Bryan Ray Augusto Tagliamacco Annalisa Innocente Gianluca Caridi Maurizio Bruschi Jayasree Hariharan Iris Fontana Antonella Trivelli Alberto Magnasco Angela Nocco Catherine Klersy Stella Muscianisi Gian Marco Ghiggeri Massimo Cardillo Enrico Verrina Arcangelo Nocera Fabrizio Ginevri Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients Frontiers in Medicine kidney transplantation non-HLA antigens autoantibodies alloantibodies antibody mediated rejection allograft loss |
| title | Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients |
| title_full | Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients |
| title_fullStr | Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients |
| title_full_unstemmed | Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients |
| title_short | Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients |
| title_sort | anti glutathione s transferase theta 1 antibodies correlate with graft loss in non sensitized pediatric kidney recipients |
| topic | kidney transplantation non-HLA antigens autoantibodies alloantibodies antibody mediated rejection allograft loss |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1035400/full |
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