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Graft versus host antibody reactions in abo unmatched renal transplants
Graft Versus Host Antibody Reactions in ABO Unmatched Renal Transplants E. Bertoni, A. Rosati, M. Zanazzi, L. Moscarelli, L. Di Maria, P. Tosi, S. Bandini, and M. Salvadori
A
DISTINCT form of graft versus host disease (GVH), manifesting as a hemolytic reaction can verify in the case of unmatched ABO allografts. This is due to donor B lymphocytes reacting against the recipient’s red cells. In 1980 Bird et al1 reported the appearance of anti–A antibodies acting as autoantibodies in the serum of a blood group A patient who received a renal transplant from a group O donor. The author mentioned the possibility that the antibodies may have been produced by the donor’s lymphocytes, which were passively transferred with the graft. A similar serological finding was noted earlier by Beck et al in a patient following lung homotransplantation.2 Since these two reports, other examples have been reported.3– 6 Typically these ABO auto antibodies are IgG, appear 7–10 days after transplantation, and last about one month. They are often responsible for hemolysis and have caused acute renal failure and, in one case, death.7 The IgG allotype eluted from the red cells of a group A woman 14 days after receiving a group O kidney demonstrated that the antibody was of donor origin and could not have been produced by the patient herself. In an exhaustive review of Ramsey,7 some 106 reported cases of ABO antibodies from transplanted solid organs were found. The frequency and severity of graft antibodies and hemolysis generally increase with the size (lymphoid content) of the organ, from kidney to liver to heart-lung transplants; the frequency of hemolysis increases also in CyA-treated kidney transplant recipients.
PATIENTS AND METHODS In our cadaver kidney retrieval and transplant program we allocated over six years 9 kidneys from group O donors to 9 group B recipients. These 9 transplant clinical courses were carefully checked for lab and clinical signs of hemolytic anemia, serum LDH, serum total bilirubin, serum aptoglobin, red blood cell and platelet counts, presence of serum anti-blood group B or anti-platelets “auto” antibodies. Actuarial graft survival was also examined. All these patients received cyclosporine (CyA) both as induction and as prophilactic therapy: 2 patients were in CyA monotherapy, 4 patients were in dual therapy (CyA plus steroids), 3 patients were in triple therapy (CyA plus steroids plus azathioprine). Four out of
these 9 patients had in the first post-transplant period a severe hemolytic anemia. All patients manifested an increase of serum total bilirubin and of serum LDH, a fall of the hematocrit and of serum aptoglobin. Anti–B serum antibodies were detected in all patients and all patients needed blood transfusion of O group. Two patients had a severe thrombocytopenia in the second month post-transplant with serum anti–platelets autoantibodies. The course of the “disease” lasted about one month and the actuarial three years graft survival rate was 100%.
RESULTS
In our experience allocating group O solid organs to group B patients often realizes a hemolytic syndrome due to antibodies generated from passenger B lymphocytes present in the graft. These ABO antibodies have almost always been short lived, with the passenger B–lymphocytes presumably becoming depleted or developing tolerance. In most cases the disease has a benign course lasting one month. This was also the case of our patients who recovered in the first month post–transplantation. According to the literature data7 patients on CyA therapy seem to have higher frequency of antibodies and of hemolysis than do patients on azathioprine. This finding supports the widely proposed idea that CyA is relatively permissive of these antibodies, probably because the secondary B– cell immune responses are generally resistant to the drug’s action. This finding raises the idea of irradiating the donor kidneys or of modifying the systemic immunosuppressive therapy in ABO unmatched transplants. Finally the occurrence in two of our patients of a hemolytic anemia with anti–B IgG followed by a IgG mediated thrombocytopenia is suggestive for a clinical condition similar to the well known Evan’s syndrome. In our patients, however, the anti– erythrocytes IgG are generated by the ABO unmatched donor passenger cells. The antiplatelets IgG are generated in the classic autoimmune pathway.
From the Renal Unit- Dept of Renal Transplantation, Careggi and University Hospital, Florence, Italy. Address reprint requests to Dr E. Bertoni, Careggi and University Hospital, Renal Unit, Viale Pieraccini 18, Villa Somma Tessa, 50139 Florence, Italy.
0041-1345/98/$19.00 PII S0041-1345(98)00632-0
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
2304
Transplantation Proceedings, 30, 2304–2305 (1998)
GRAFT VS HOST ANTIBODY REACTIONS
REFERENCES 1. Bird GWG, Wingham J: Immunol Commun: 9:155, 1980 2. Beck ML, Haines RF, Oberman HA: Proc 24th Annual Meeting AABB: Chicago. No publisher 1971, p 98 3. Lundgren G, Asaba H, Bergstrom: J Clin Nephrol 16:211, 1981
2305 4. Nyberg G, Saadberg L, Rydberg L, et al: Transplantation 37:529, 1984 5. Mangal AK, Growe GH, Sinclair M, et al: Transfusion 24:201, 1984 6. Bevan PC, Seaman M, Tolliday B, et al: Vox Sang 49:42, 1985 7. Ramsey G: Transfusion 31:76, 1991
A
DISTINCT form of graft versus host disease (GVH), manifesting as a hemolytic reaction can verify in the case of unmatched ABO allografts. This is due to donor B lymphocytes reacting against the recipient’s red cells. In 1980 Bird et al1 reported the appearance of anti–A antibodies acting as autoantibodies in the serum of a blood group A patient who received a renal transplant from a group O donor. The author mentioned the possibility that the antibodies may have been produced by the donor’s lymphocytes, which were passively transferred with the graft. A similar serological finding was noted earlier by Beck et al in a patient following lung homotransplantation.2 Since these two reports, other examples have been reported.3– 6 Typically these ABO auto antibodies are IgG, appear 7–10 days after transplantation, and last about one month. They are often responsible for hemolysis and have caused acute renal failure and, in one case, death.7 The IgG allotype eluted from the red cells of a group A woman 14 days after receiving a group O kidney demonstrated that the antibody was of donor origin and could not have been produced by the patient herself. In an exhaustive review of Ramsey,7 some 106 reported cases of ABO antibodies from transplanted solid organs were found. The frequency and severity of graft antibodies and hemolysis generally increase with the size (lymphoid content) of the organ, from kidney to liver to heart-lung transplants; the frequency of hemolysis increases also in CyA-treated kidney transplant recipients.
PATIENTS AND METHODS In our cadaver kidney retrieval and transplant program we allocated over six years 9 kidneys from group O donors to 9 group B recipients. These 9 transplant clinical courses were carefully checked for lab and clinical signs of hemolytic anemia, serum LDH, serum total bilirubin, serum aptoglobin, red blood cell and platelet counts, presence of serum anti-blood group B or anti-platelets “auto” antibodies. Actuarial graft survival was also examined. All these patients received cyclosporine (CyA) both as induction and as prophilactic therapy: 2 patients were in CyA monotherapy, 4 patients were in dual therapy (CyA plus steroids), 3 patients were in triple therapy (CyA plus steroids plus azathioprine). Four out of
these 9 patients had in the first post-transplant period a severe hemolytic anemia. All patients manifested an increase of serum total bilirubin and of serum LDH, a fall of the hematocrit and of serum aptoglobin. Anti–B serum antibodies were detected in all patients and all patients needed blood transfusion of O group. Two patients had a severe thrombocytopenia in the second month post-transplant with serum anti–platelets autoantibodies. The course of the “disease” lasted about one month and the actuarial three years graft survival rate was 100%.
RESULTS
In our experience allocating group O solid organs to group B patients often realizes a hemolytic syndrome due to antibodies generated from passenger B lymphocytes present in the graft. These ABO antibodies have almost always been short lived, with the passenger B–lymphocytes presumably becoming depleted or developing tolerance. In most cases the disease has a benign course lasting one month. This was also the case of our patients who recovered in the first month post–transplantation. According to the literature data7 patients on CyA therapy seem to have higher frequency of antibodies and of hemolysis than do patients on azathioprine. This finding supports the widely proposed idea that CyA is relatively permissive of these antibodies, probably because the secondary B– cell immune responses are generally resistant to the drug’s action. This finding raises the idea of irradiating the donor kidneys or of modifying the systemic immunosuppressive therapy in ABO unmatched transplants. Finally the occurrence in two of our patients of a hemolytic anemia with anti–B IgG followed by a IgG mediated thrombocytopenia is suggestive for a clinical condition similar to the well known Evan’s syndrome. In our patients, however, the anti– erythrocytes IgG are generated by the ABO unmatched donor passenger cells. The antiplatelets IgG are generated in the classic autoimmune pathway.
From the Renal Unit- Dept of Renal Transplantation, Careggi and University Hospital, Florence, Italy. Address reprint requests to Dr E. Bertoni, Careggi and University Hospital, Renal Unit, Viale Pieraccini 18, Villa Somma Tessa, 50139 Florence, Italy.
0041-1345/98/$19.00 PII S0041-1345(98)00632-0
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
2304
Transplantation Proceedings, 30, 2304–2305 (1998)
GRAFT VS HOST ANTIBODY REACTIONS
REFERENCES 1. Bird GWG, Wingham J: Immunol Commun: 9:155, 1980 2. Beck ML, Haines RF, Oberman HA: Proc 24th Annual Meeting AABB: Chicago. No publisher 1971, p 98 3. Lundgren G, Asaba H, Bergstrom: J Clin Nephrol 16:211, 1981
2305 4. Nyberg G, Saadberg L, Rydberg L, et al: Transplantation 37:529, 1984 5. Mangal AK, Growe GH, Sinclair M, et al: Transfusion 24:201, 1984 6. Bevan PC, Seaman M, Tolliday B, et al: Vox Sang 49:42, 1985 7. Ramsey G: Transfusion 31:76, 1991