ABO Blood Group Incompatibility in Human Renal Homotransplantation

Wilbrandt, Rupert; Tung, Kenneth S. K.; Deodhar, Sharad D.; Nakamoto, Satoru; Kolff, Willem J.

doi:10.1093/ajcp/51.1.15

Cited by 55 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12,41,42 ABO incompatibility is presently one of the major limiting factors in transplantation of allografts in humans. [43][44][45][46] By using autologous lymphocytes transduced with adenovirus containing A or B transferase gene, 47 one may induce tolerance similar to that observed with AdaGT transduced lymphocytes. As with tolerance induction to the a-gal epitope, such a treatment is likely to require depletion of the corresponding anti-blood group antibody, prior to the administration of the transduced lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Induction of immune tolerance to a transplantation carbohydrate antigen by gene therapy with autologous lymphocytes transduced with adenovirus containing the corresponding glycosyltransferase gene

Ogawa

Galili

2004

Gene Ther

View full text Add to dashboard Cite

Induction of tolerance to transplantation carbohydrate antigens is of clinical significance in recipients of ABOincompatible allografts, or of xenografts. The experimental animal model used for studying such tolerance was that of a1,3galactosyltransferase (a1,3GT) knockout (KO) mice, which lacks the a-gal epitope (Gala1-3Galb1-4GlcNAc-R) and which can produce the anti-Gal antibody against it. In contrast, wild-type (WT) mice synthesize the a-gal epitope and are immunotolerant to it. KO lymphocytes transduced in vitro with adenovirus containing the a1,3GT gene (AdaGT) express a-gal epitopes. Administration of such lymphocytes into KO mice resulted in tolerization of naïve and memory anti-Gal B cells. Mice tolerized by AdaGT transduced lymphocytes failed to produce anti-Gal following immunizations with pig kidney membranes (PKM) expressing multiple a-gal epitopes. This tolerance was perpetuated by transplanted syngeneic WT mouse hearts expressing a-gal epitopes. Transplanted WT hearts survived in the tolerized KO mice for at least 100 days, despite repeated PKM immunizations. Control mice receiving lymphocytes transduced with adenovirus lacking the a1,3GT gene were not tolerized, but produced anti-Gal and rejected transplanted WT hearts. This study suggests that autologous lymphocytes transduced with adenovirus containing A or B transferase genes may induce a similar tolerance to blood group antigens in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of immune tolerance to a transplantation carbohydrate antigen by gene therapy with autologous lymphocytes transduced with adenovirus containing the corresponding glycosyltransferase gene

Ogawa

Galili

2004

Gene Ther

View full text Add to dashboard Cite

show abstract

“…Previous studies have suggested that early graft loss after ABOi-KT may be due to attack of recipient-specific anti-A/B antibodies, including ABH antigens [711]. This phenomenon was later referred to as antibody-mediated rejection (ABMR) and defined as allograft rejection caused by antibodies directed against donor-specific antigens [12].…”

Section: Introductionmentioning

confidence: 99%

Effects of Neutralization by Soluble ABH Antigens Produced by Transplanted Kidneys From ABO-Incompatible Secretor Donors

Kim

Hwang

et al. 2017

Ann Lab Med

View full text Add to dashboard Cite

BackgroundGrafts survive despite blood group antigens on the transplant being continuously exposed to antibodies in the blood of recipients in ABO-incompatible kidney transplantation (ABOi KT), owing to the mechanism of accommodation. We analyzed the immunodynamics of soluble ABH antigens in allografts from secretor donors and the influence of such immunodynamics on accommodation and subsequent graft survival in ABOi KT.MethodsThe genotype of a known human β-galactoside α-1,2-fucosyltransferase gene (FUT2), which determines soluble ABH antigen secretor status, was established in 32 donors for ABOi KT at the Severance Hospital, from June 2010 to July 2015. Clinical outcomes of recipients, such as anti-A/B antibody titer change, renal function, and graft survival, were evaluated.ResultsTwenty-five donors were secretors (78.1%), and seven were nonsecretors (21.9%). The frequency of anti-A/B IgG or IgM antibody titer elevation or reduction post-transplantation was not significantly related to donor secretor status. However, IgM titer was rapidly reduced in recipients transplanted from nonsecretor donors (P=0.01), which could be explained by the lack of absorption effect of soluble antigens, enhancing the binding of antibodies to antigens in the allografts. Interestingly, soluble ABH antigens did not affect rejection-free graft survival, which may be due to the nature of β-galactoside α-1,2-fucosyltransferase.ConclusionsSoluble ABH antigens produced by transplanted kidneys from secretor donors played a role in inducing accommodation within three months of KT through neutralization; however, major graft outcomes were not affected.

show abstract

“…Until the 1980s, transplantation of organs, particularly kidneys across ABO-blood group barriers (eg a kidney from an individual of blood group-A and/or -B transplanted into a recipient with iso-antibodies specific for one or both blood group antigens) was generally discouraged. 104,105 Graft failure was understood to be triggered by the binding of anti-blood group antibodies, which immune competent adults have 25 to foreign blood group-A and/or -B antigen, 106 which is expressed on endothelial cells. 104,105 Graft failure was understood to be triggered by the binding of anti-blood group antibodies, which immune competent adults have 25 to foreign blood group-A and/or -B antigen, 106 which is expressed on endothelial cells.…”

Section: Accommodationmentioning

confidence: 99%

The five dimensions of B cell tolerance

Platt

Barbosa

Cascalho

2019

Immunological Reviews

View full text Add to dashboard Cite

B cell tolerance has been generally understood to be an acquired property of the immune system that governs antibody specificity in ways that avoid auto-toxicity.As useful as this understanding has proved, it fails to fully explain the existence of auto-reactive specificities in healthy individuals and contribution these may have to health. Mechanisms underlying B cell tolerance are considered to select a clonal repertoire that generates a collection of antibodies that do not bind self, ie tolerance operates more or less in three dimensions that largely spare autologous cells andantigens. Yet, most B lymphocytes in humans and probably in other vertebrates are auto-reactive and absence of these auto-reactive B cells is associated with disease.We suggest that auto-reactivity can be embodied by extending the concept of tolerance by two further dimensions, one of time and circumstance and one that allows healthy cells to actively resist injury. In this novel concept, macromolecular recognition by the B cell receptor leading to deletion, anergy, receptor editing or B cell activation is extended by taking account of the time of development of normal immune responses (4th dimension) and the accommodation (or tolerance) of normal cells to bound antibody, activation of complement, and interaction with inflammatory cells (fifth dimension). We discuss how these dimensions contribute to understanding B cell biology in health or disease. K E Y W O R D S

show abstract

ABO Blood Group Incompatibility in Human Renal Homotransplantation

Cited by 55 publications

References 0 publications

Induction of immune tolerance to a transplantation carbohydrate antigen by gene therapy with autologous lymphocytes transduced with adenovirus containing the corresponding glycosyltransferase gene

Induction of immune tolerance to a transplantation carbohydrate antigen by gene therapy with autologous lymphocytes transduced with adenovirus containing the corresponding glycosyltransferase gene

Effects of Neutralization by Soluble ABH Antigens Produced by Transplanted Kidneys From ABO-Incompatible Secretor Donors

The five dimensions of B cell tolerance

Contact Info

Product

Resources

About