Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation

Le, Hoa; Treilhaud, M.; Ben-Arye, Shani Leviatan; Yu, Hai; Perreault, Hélène; Ang, Evelyn; Trébern-Launay, Katy; Laurent, Julie; Malard-Castagnet, Stéphanie; Cesbron, Anne; Nguyen, Thi Van Ha; Brouard, Sophie; Rostaing, Lionel; Houssel‐Debry, Pauline; Legendre, Christophe; Girerd, Sophie; Kessler, Michèle; Morélon, Emmanuel; Sicard, A; Garrigue, Valérie; Karam, Georges; Chen, Xi; Giral, Magali; Padler‐Karavani, Vered; Soulillou, Jean Paul

doi:10.1097/txd.0000000000000772

Cited by 12 publications

(21 citation statements)

References 17 publications

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“…In this case, circulating anti-Neu5Gc antibodies could reduce efficacy of therapy, [134][135][136] elicit an increased and diversified anti-Neu5Gc response that can remain long-lasting, 143,144 or possibly mediate xenograft failure or rejection. 104,136,142,145 Currently, it seems that both the αGal and Neu5Gc-glycans limit the potential of xenotransplantation, as recently reviewed elsewhere, 103,104,[146][147][148] and generation of double-knockout animals deficient in both the CMAH and GGTA1 genes seems to be promising. 139,147,[149][150][151]…”

Section: Con S Equen Ce S Of Neu5g C and Anti -Neu5g C Antibod Ie Smentioning

confidence: 99%

Evolution of sialic acids: Implications in xenotransplant biology

Paul

Padler‐Karavani

2018

Xenotransplantation

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All living cells are covered with a dense "sugar-coat" of carbohydrate chains (glycans) conjugated to proteins and lipids. The cell surface glycome is determined by a non-template driven process related to the collection of enzymes that assemble glycans in a sequential manner. In mammals, many of these glycans are topped with sialic acids (Sia), a large family of acidic sugars. The "Sialome" is highly diverse owing to various Sia types, linkage to underlying glycans, range of carriers, and complex spatial organization. Presented at the front of cells, Sia play a major role in immunity and recognition of "self" versus "non-self," largely mediated by the siglecs family of Sia-binding host receptors. Albeit many mammalian pathogens have evolved to hijack this recognition system to avoid host immune attack, presenting a fascinating host-pathogen evolutionary arms race. Similarly, cancer cells exploit Sia for their own survival and propagation. As part of this ongoing fitness, humans lost the ability to synthesize the Sia type N-glycolylneuraminic acid (Neu5Gc), in contrast to other mammals. While this loss had provided an advantage against certain pathogens, humans are continuously exposed to Neu5Gc through mammalian-derived diet (eg, red meat), consequently generating a complex immune response against it. Circulating anti-Neu5Gc antibodies together with Neu5Gc on some human tissues mediate chronic inflammation "xenosialitis" that exacerbate various human diseases (eg, cancer and atherosclerosis). Similarly, Neu5Gc-containing xenografts are exposed to human anti-Neu5Gc antibodies with implications to sustainability. This review aimed to provide a glimpse into the evolution of Sia and their implications to xenotransplantation.

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Section: Con S Equen Ce S Of Neu5g C and Anti -Neu5g C Antibod Ie Smentioning

confidence: 99%

Evolution of sialic acids: Implications in xenotransplant biology

Paul

Padler‐Karavani

2018

Xenotransplantation

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“…The comparison with patients who received Basiliximab did not reach a significant difference, suggesting that despite the negative mass spectrometry patterns on Basiliximab, traces of xeno‐glycans are immunogenic.…”

Section: Discussionmentioning

confidence: 90%

“…This confirmed the hierarchy of response still favouring anti-Neu5Gc compared to anti-Gal in strongly immunosuppressed patients. 13 The comparison with patients who received Basiliximab did not reach a significant difference, suggesting that despite the negative mass spectrometry patterns on Basiliximab, 28 traces of xeno-glycans 30,31 are immunogenic.…”

Section: Discussionmentioning

confidence: 92%

“…More specifically, serial changes in anti‐Neu5Gc and anti‐Gal IgG levels (Figure B,C, respectively) showed a reduction in antibody levels at T6 (paired t test P = 0.0003 and P < 0.0001, respectively) compared to the pre‐existing levels, a decrease still detectable at T12 ( P = 0.03 and P = 0.0005, respectively). Comparisons of anti‐ATG, anti‐Gal and anti‐Neu5Gc IgG titres were also performed on the patients without ATG as a whole, as well as independently in the two control subgroups of recipients with no induction (n = 15) or with Basiliximab (Simulect, n = 15) induction(Figure ) owing the fact that Basiliximab does not carry Neu5Gc epitope . There was an increase in anti‐Gal IgG between T6 and T12 for the group without induction ( P = 0.03, Figure E).…”

Section: Resultsmentioning

confidence: 99%

“…Comparisons of anti-ATG, anti-Gal and anti-Neu5Gc IgG titres were also performed on the patients without ATG as a whole, as well as independently in the two control subgroups of recipients with no induction (n = 15) or with Basiliximab (Simulect, n = 15) induction( Figure S2) owing the fact that Basiliximab does not carry Neu5Gc epitope. 28 There was an increase in anti-Gal IgG between T6 and T12 for the group without induction (P = 0.03, Figure S2E). For anti-Neu5Gc IgG levels, there was a decrease between T0 and T12 months in the group with Basiliximab induction (P = 0.0098, Figure S2D).…”

Section: Serial Comparison Of Anti-atg Antibody Levels In the Diffementioning

confidence: 92%

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Quantitative and qualitative changes in anti‐Neu5Gc antibody response following rabbit anti‐thymocyte IgG induction in kidney allograft recipients

Rousse¹,

Salama²,

Ben-Arye

et al. 2019

Eur J Clin Investigation

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Antibodies of non‐human mammals are glycosylated with carbohydrate antigens, such as galactose‐α‐1‐3‐galactose (α‐Gal) and N‐glycolylneuraminic acid (Neu5Gc). These non‐human carbohydrate antigens are highly immunogenic in humans due to loss‐of‐function mutations of the key genes involved in their synthesis. Such immunogenic carbohydrates are expressed on therapeutic polyclonal rabbit anti‐human T‐cell IgGs (anti‐thymocyte globulin; ATG), the most popular induction treatment in allograft recipients. To decipher the quantitative and qualitative response against these antigens in immunosuppressed patients, particularly against Neu5Gc, which may induce endothelial inflammation in both the graft and the host. We report a prospective study of the antibody response against α‐Gal and Neu5Gc‐containing glycans following rabbit ATG induction compared to controls. We show a drop in the overall levels of anti‐Neu5Gc antibodies at 6 and 12 months post‐graft compared to the pre‐existing levels due to the major early immunosuppression. However, in contrast, in a cross‐sectional study there was a highly significant increase in anti‐Neu5Gc IgGs levels at 6 months post‐graft in the ATG‐treated compared to non‐treated patients(P = 0.007), with a clear hierarchy favouring anti‐Neu5Gc over anti‐Gal response. A sialoglycan microarray analysis revealed that the increased anti‐Neu5Gc IgG response was still highly diverse against multiple different Neu5Gc‐containing glycans. Furthermore, some of the ATG‐treated patients developed a shift in their anti‐Neu5Gc IgG repertoire compared with the baseline, recognizing different patterns of Neu5Gc‐glycans. In contrast to Gal, Neu5Gc epitopes remain antigenic in severely immunosuppressed patients, who also develop an anti‐Neu5Gc repertoire shift. The clinical implications of these observations are discussed.

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Outcomes of Kidney Allograft and Recipient Survival After Liver Transplantation by Induction Type in the United States

et al. 2021

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There are several choices for induction immunosuppression in kidney-after-liver transplantation. We used the Scientific Registry of Transplant Recipients database. We assessed all kidney-after-liver transplant recipients in the United States between 1/1/2000 and 7/31/2017 to study kidney graft and patient outcomes by induction type. We only included patients discharged on tacrolimus and mycophenolate with or without steroids and had a negative crossmatch before kidney engraftment. We grouped recipients by kidney induction type into the following 3 groups: depletional (n = 550), nondepletional (n = 434), and no antibody induction (n = 144). We studied patient and kidney allograft survival using Cox proportional hazard regression, with transplant center included as a random effect. Models were adjusted for liver induction regimen, recipient and donor age, sex, human leukocyte antigen mismatches, payor type, living donor kidney transplantation, dialysis status, time from liver engraftment, hepatitis C virus status, and the presence of diabetes mellitus at time of kidney transplantation and transplantation year. The 6-month and 1-year rejection rates did not differ between groups. Compared with no induction, neither depletional nor nondepletional induction was associated with an improved recipient or graft survival in the multivariable models. Depletional induction at the time of liver transplantation was associated with worse patient survival after kidney transplantation (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.09-2.67; P = 0.02). Living donor kidney transplantation was associated with a 48.1% improved graft survival (HR, 0.52; 95% CI, 0.33-0.82; P = 0.00). In conclusion, in the settings of a negative cross-match and maintenance with tacrolimus and mycophenolate, induction use was not associated with a patient or graft survival benefit in kidney-after-liver transplantations.

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Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation

Abstract: Supplemental digital content is available in the text.

Cited by 12 publications

References 17 publications

Evolution of sialic acids: Implications in xenotransplant biology

Evolution of sialic acids: Implications in xenotransplant biology

Quantitative and qualitative changes in anti‐Neu5Gc antibody response following rabbit anti‐thymocyte IgG induction in kidney allograft recipients

Outcomes of Kidney Allograft and Recipient Survival After Liver Transplantation by Induction Type in the United States

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