PMID- 36530923 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221222 IS - 2296-858X (Print) IS - 2296-858X (Electronic) IS - 2296-858X (Linking) VI - 9 DP - 2022 TI - Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients. PG - 1035400 LID - 10.3389/fmed.2022.1035400 [doi] LID - 1035400 AB - INTRODUCTION: Immunity 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. METHODS: We 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). RESULTS: We 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. DISCUSSION: Our 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. CI - Copyright (c) 2022 Comoli, Cioni, Ray, Tagliamacco, Innocente, Caridi, Bruschi, Hariharan, Fontana, Trivelli, Magnasco, Nocco, Klersy, Muscianisi, Ghiggeri, Cardillo, Verrina, Nocera and Ginevri. FAU - Comoli, Patrizia AU - Comoli P AD - UOSD Cell Factory and UOC Pediatric Hematology/Oncology, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. FAU - Cioni, Michela AU - Cioni M AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. FAU - Ray, Bryan AU - Ray B AD - Immucor Inc., Norcross, GA, United States. FAU - Tagliamacco, Augusto AU - Tagliamacco A AD - Transplantation Immunology, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. FAU - Innocente, Annalisa AU - Innocente A AD - Transplantation Immunology, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. FAU - Caridi, Gianluca AU - Caridi G AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. FAU - Bruschi, Maurizio AU - Bruschi M AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. FAU - Hariharan, Jayasree AU - Hariharan J AD - Immucor Inc., Norcross, GA, United States. FAU - Fontana, Iris AU - Fontana I AD - Vascular and Endovascular Unit and Kidney Transplant Surgery Unit, IRCCS San Martino University Hospital IST, University of Genoa, Genoa, Italy. FAU - Trivelli, Antonella AU - Trivelli A AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. FAU - Magnasco, Alberto AU - Magnasco A AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. FAU - Nocco, Angela AU - Nocco A AD - Transplantation Immunology, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. FAU - Klersy, Catherine AU - Klersy C AD - Biometry and Statistics Service, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. FAU - Muscianisi, Stella AU - Muscianisi S AD - UOSD Cell Factory and UOC Pediatric Hematology/Oncology, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. FAU - Ghiggeri, Gian Marco AU - Ghiggeri GM AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. FAU - Cardillo, Massimo AU - Cardillo M AD - Italian National Transplant Centre, Italian National Institute of Health (ISS), Rome, Italy. FAU - Verrina, Enrico AU - Verrina E AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. FAU - Nocera, Arcangelo AU - Nocera A AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. FAU - Ginevri, Fabrizio AU - Ginevri F AD - Nephrology, Dialysis and Transplantation Unit, Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy. LA - eng PT - Journal Article DEP - 20221130 PL - Switzerland TA - Front Med (Lausanne) JT - Frontiers in medicine JID - 101648047 PMC - PMC9748144 OTO - NOTNLM OT - alloantibodies OT - allograft loss OT - antibody mediated rejection OT - autoantibodies OT - kidney transplantation OT - non-HLA antigens COIS- Authors BR and JH were employed by Immucor Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/20 06:00 MHDA- 2022/12/20 06:01 PMCR- 2022/11/30 CRDT- 2022/12/19 03:39 PHST- 2022/09/02 00:00 [received] PHST- 2022/11/14 00:00 [accepted] PHST- 2022/12/19 03:39 [entrez] PHST- 2022/12/20 06:00 [pubmed] PHST- 2022/12/20 06:01 [medline] PHST- 2022/11/30 00:00 [pmc-release] AID - 10.3389/fmed.2022.1035400 [doi] PST - epublish SO - Front Med (Lausanne). 2022 Nov 30;9:1035400. doi: 10.3389/fmed.2022.1035400. eCollection 2022.