Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 May;25(3):e12418.
doi: 10.1111/xen.12418.

Accommodation in ABO-incompatible Organ Transplants

Affiliations
Free PMC article
Review

Accommodation in ABO-incompatible Organ Transplants

Mayara Garcia de Mattos Barbosa et al. Xenotransplantation. .
Free PMC article

Abstract

Accommodation refers to a condition in which a transplant (or any tissue) appears to resist immune-mediated injury and loss of function. Accommodation was discovered and has been explored most thoroughly in ABO-incompatible kidney transplantation. In this setting, kidney transplants bearing blood group A or B antigens often are found to function normally in recipients who lack and hence produce antibodies directed against the corresponding antigens. Whether accommodation is owed to changes in anti-blood group antibodies, changes in antigen or a change in the response of the transplant to antibody binding are critically reviewed and a new working model that allows for the kinetics of development of accommodation is put forth. Regardless of how accommodation develops, observations on the fate of ABO-incompatible transplants offer lessons applicable more broadly in transplantation and in other fields.

Keywords: ABO-incompatible transplant; accommodation; blood group; blood type; kidney transplant; rejection.

Figures

Figure 1
Figure 1. Chronology of rejection and accommodation of ABO-incompatible kidney transplants. A. Rejection of ABO-incompatible kidney transplants
Ischemia-reperfusion injury and antibodies directed against donor blood group and possibly against HLA antigens activate the complement system. If complement activation from this combination of factors is robust and fast, hyperacute rejection may ensue within minutes to hours of the time reperfusion. Today, hyperacute rejection is rare because of cross matching and depletion of anti-blood group antibodies. However, lower levels of these antibodies can induce early acute vascular rejection. After several weeks, however, the risk of rejection of an ABO-incompatible graft is no higher than that of an ABO-compatible graft. One explanation for the decrease in the risk of rejection may be “accommodation” of the graft to ongoing presence of anti-blood group antibodies in the recipient. B. Accommodation of ABO-incompatible kidney transplants. ABO-incompatible kidney transplants exhibit heightened risk of antibody-mediated rejection during the first several weeks up to approximately one month after transplantation. This risk reflects the ongoing production of antibodies specific for blood group antigens in the graft. Susceptibility to early rejection (and ischemia-reperfusion injury) is mitigated by intrinsic resistance of nucleated cells and tissues to complement mediated injury and by the immediate response to complement activation on cell surfaces. Over a period of weeks, grafts acquire a higher level of resistance to injury by antibodies and complement. This heightened resistance reflects in part the repair of damage already inflicted and in part changes at the cellular and tissue level that reduce susceptibility to injury. The condition in which a tissue or organ resists otherwise lethal injury by complement or other factors is called “accommodation.”
Figure 2
Figure 2. Concentration of anti-blood group antibodies in the blood before and after kidney transplantation
Originally published by Hume et al. (Annals of the NY Academy of Sciences 120: 578, 1964) with permission of the publisher (John Wiley & Sons). The figure (modified for clarity) depicts the concentration of anti-blood group B antibodies (1/titer determined using 2-fold dilutions, i.e. the reciprocal log2) in a patient of blood group A before and after transplantation of a kidney from a donor of blood group B (solid line). Also shown are the concentrations of anti-blood group B antibodies in two controls, patients of blood group O who received kidney transplants from donors of blood group O (dashed lines). The figure shows that immediately upon transplantation, antibodies against donor blood group B are depleted from the blood (arrow; from 1:1024 to ~1:25) and within 12 hours are undetectable. The figure also shows that anti-donor blood group antibodies are detected again 5 days after transplantation, likely the time that function deteriorates from rejection. On day 7, urinary output decreased, presumably from rejection. In two controls (blood type O kidneys in blood type O recipients) the levels of anti-blood group B antibodies do not change notably after transplantation. The figure shows that a functioning transplant depletes all or nearly all anti-blood group antibody from a recipient.
Figure 3
Figure 3. Lysis of human erythrocytes by blood group-incompatible serum is a direct function of the concentration of anti-blood group antibodies and concentration of complement
The illustrations are from the US Army Medical Research Laboratory Report #818 (90) and are presented with permission. A. Lysis of human erythrocytes is a function of the concentration of anti-blood group antibodies used to activate human complement. Three dilutions of a reference serum, used as a source of anti-blood group A antibodies were used to determine the QH50, the dilution of a serum that lyses 50% of a standard red cell suspension (QH50) in the presence of excess complement. The QH50 for the three dilutions (shown at the bottom) indicate that lysis is a direct and predictable function of the concentration of anti-A antibodies. B. Assay of various sources of human complement for ability to lyse erythrocytes when combined with serial dilutions of serum from an individual of blood group O. A standard volume (0.1 ml) of serum containing anti-A or anti-B antibodies is combined with various volumes of absorbed human serum lacking anti-A or -B antibodies (i.e. human complement) and added to a standard preparation of washed A- or B-type erythrocytes. The figure shows that lysis is a function of the amount of human complement added.
Figure 3
Figure 3. Lysis of human erythrocytes by blood group-incompatible serum is a direct function of the concentration of anti-blood group antibodies and concentration of complement
The illustrations are from the US Army Medical Research Laboratory Report #818 (90) and are presented with permission. A. Lysis of human erythrocytes is a function of the concentration of anti-blood group antibodies used to activate human complement. Three dilutions of a reference serum, used as a source of anti-blood group A antibodies were used to determine the QH50, the dilution of a serum that lyses 50% of a standard red cell suspension (QH50) in the presence of excess complement. The QH50 for the three dilutions (shown at the bottom) indicate that lysis is a direct and predictable function of the concentration of anti-A antibodies. B. Assay of various sources of human complement for ability to lyse erythrocytes when combined with serial dilutions of serum from an individual of blood group O. A standard volume (0.1 ml) of serum containing anti-A or anti-B antibodies is combined with various volumes of absorbed human serum lacking anti-A or -B antibodies (i.e. human complement) and added to a standard preparation of washed A- or B-type erythrocytes. The figure shows that lysis is a function of the amount of human complement added.
Figure 4
Figure 4. Intravascular hemolysis of blood group A- and blood group B-incompatible erythrocytes in human subjects
This figure depicts classic experiments performed to ascertain the mechanism of clearance of blood group A and blood group B erythrocytes administered to human subjects with the corresponding anti-blood group antibodies. Depending on the isotype and concentration of anti-A or -B blood group antibodies and the antigen density and the number of cells administered, clearance might be generated by immediate complement-mediated lysis (intravascular hemolysis) or by sequestration by phagocytes in spleen, liver or blood. In the examples shown, erythrocytes are labeled in vitro with 51Cr and then a small volume (<1 ml) is given intravenously. A. Intravascular hemolysis of 51Cr-labeled blood group A and blood group B erythrocytes within minutes after administration to subjects with anti-A and anti-B antibodies. Hemolysis occurs even in subjects whose antibody titers are too low to generate hemolysis in vitro. The table is from M. Cutbush and P.L. Mollison, Brit J Haemat 4: 115, 1965 with permission of the publisher (John Wiley & Sons). B. Intravascular hemolysis 51Cr-labeled erythrocytes of blood group B administered to a subject of blood group (open circles) and 51Cr-labeled blood group A2 erythrocytes into a subject of blood group O (solid circles). Erythrocytes of blood group A2 have less antigen but intravascular hemolysis still occurs to the same extent (>99%), if slightly less quickly. From Mollison’s Blood Transfusion in Clinical Medicine eleventh ed., H. G. Klein and D.J. Anstee (2005), Chapter 10, Fig 10.3. C. Laboratory findings after transfusion of 140 ml of blood group A2 erythrocytes into a patient of blood group O. Although the density of blood group A2 antigen is low, sufficient antibody is bound to decrease the concentration 32-fold (1:512 to 1:16) and to cause activation of complement and intravascular hemolysis, indicated by the presence of hemoglobin in plasma and urine. Some erythrocytes were cleared by phagocytosis indicated by the increase in bilirubin. The table is from C.P. Duvall et al. Transfusion 14: 382, 1974, with permission of the publisher, John Wiley & Sons.
Figure 4
Figure 4. Intravascular hemolysis of blood group A- and blood group B-incompatible erythrocytes in human subjects
This figure depicts classic experiments performed to ascertain the mechanism of clearance of blood group A and blood group B erythrocytes administered to human subjects with the corresponding anti-blood group antibodies. Depending on the isotype and concentration of anti-A or -B blood group antibodies and the antigen density and the number of cells administered, clearance might be generated by immediate complement-mediated lysis (intravascular hemolysis) or by sequestration by phagocytes in spleen, liver or blood. In the examples shown, erythrocytes are labeled in vitro with 51Cr and then a small volume (<1 ml) is given intravenously. A. Intravascular hemolysis of 51Cr-labeled blood group A and blood group B erythrocytes within minutes after administration to subjects with anti-A and anti-B antibodies. Hemolysis occurs even in subjects whose antibody titers are too low to generate hemolysis in vitro. The table is from M. Cutbush and P.L. Mollison, Brit J Haemat 4: 115, 1965 with permission of the publisher (John Wiley & Sons). B. Intravascular hemolysis 51Cr-labeled erythrocytes of blood group B administered to a subject of blood group (open circles) and 51Cr-labeled blood group A2 erythrocytes into a subject of blood group O (solid circles). Erythrocytes of blood group A2 have less antigen but intravascular hemolysis still occurs to the same extent (>99%), if slightly less quickly. From Mollison’s Blood Transfusion in Clinical Medicine eleventh ed., H. G. Klein and D.J. Anstee (2005), Chapter 10, Fig 10.3. C. Laboratory findings after transfusion of 140 ml of blood group A2 erythrocytes into a patient of blood group O. Although the density of blood group A2 antigen is low, sufficient antibody is bound to decrease the concentration 32-fold (1:512 to 1:16) and to cause activation of complement and intravascular hemolysis, indicated by the presence of hemoglobin in plasma and urine. Some erythrocytes were cleared by phagocytosis indicated by the increase in bilirubin. The table is from C.P. Duvall et al. Transfusion 14: 382, 1974, with permission of the publisher, John Wiley & Sons.
Figure 4
Figure 4. Intravascular hemolysis of blood group A- and blood group B-incompatible erythrocytes in human subjects
This figure depicts classic experiments performed to ascertain the mechanism of clearance of blood group A and blood group B erythrocytes administered to human subjects with the corresponding anti-blood group antibodies. Depending on the isotype and concentration of anti-A or -B blood group antibodies and the antigen density and the number of cells administered, clearance might be generated by immediate complement-mediated lysis (intravascular hemolysis) or by sequestration by phagocytes in spleen, liver or blood. In the examples shown, erythrocytes are labeled in vitro with 51Cr and then a small volume (<1 ml) is given intravenously. A. Intravascular hemolysis of 51Cr-labeled blood group A and blood group B erythrocytes within minutes after administration to subjects with anti-A and anti-B antibodies. Hemolysis occurs even in subjects whose antibody titers are too low to generate hemolysis in vitro. The table is from M. Cutbush and P.L. Mollison, Brit J Haemat 4: 115, 1965 with permission of the publisher (John Wiley & Sons). B. Intravascular hemolysis 51Cr-labeled erythrocytes of blood group B administered to a subject of blood group (open circles) and 51Cr-labeled blood group A2 erythrocytes into a subject of blood group O (solid circles). Erythrocytes of blood group A2 have less antigen but intravascular hemolysis still occurs to the same extent (>99%), if slightly less quickly. From Mollison’s Blood Transfusion in Clinical Medicine eleventh ed., H. G. Klein and D.J. Anstee (2005), Chapter 10, Fig 10.3. C. Laboratory findings after transfusion of 140 ml of blood group A2 erythrocytes into a patient of blood group O. Although the density of blood group A2 antigen is low, sufficient antibody is bound to decrease the concentration 32-fold (1:512 to 1:16) and to cause activation of complement and intravascular hemolysis, indicated by the presence of hemoglobin in plasma and urine. Some erythrocytes were cleared by phagocytosis indicated by the increase in bilirubin. The table is from C.P. Duvall et al. Transfusion 14: 382, 1974, with permission of the publisher, John Wiley & Sons.
Figure 5
Figure 5. Relationship or lack thereof between the concentrations of IgM and IgG specific for blood group A in a kidney transplant and function of the transplant
A patient of blood group O received a kidney transplant from a donor of blood group A and the levels of IgM and IgG in the recipient specific for blood group A and the serum creatinine (an inverse measure of renal function) were measured at various times after transplantation. Repeated biopsies confirmed the continued expression of blood group A on donor endothelium (not shown). The figure depicts these values at times other than those immediately following antibody depletion. The results reveal absolutely no relationship between the levels of antibodies directed against donor blood groups and the function of the transplant in contrast to the impact of anti-blood group antibodies on erythrocytes depicted in Figures 2–4.

Similar articles

See all similar articles

Cited by 6 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback