Type A subgroup is rare in Japan, and kidney transplant to a type A subgroup recipient is rare worldwide. A 65-year-old man presented for living-donor kidney transplant. Blood group testing showed that his wife (kidney donor) had blood group type A. The patient (recipient) had a type A subgroup because reverse blood grouping showed a weak reaction with A₁ antigen. Further testing showed that the recipient had type A subgroup between A_x and A_el because adsorption elution experiments and flow cytometry showed a few A antigens that were not detected on forward grouping, and DNA analysis was not consistent with A_el. The patient was given a milder protocol for immunosuppressive preoperative therapy than typically used for ABO-incompatible kidney trans-plant; mycophenolate mofetil and prednisolone were started 3 weeks and cyclosporine 2 weeks before transplant, rituximab (100 mg) was given once, and double filtration plasmapheresis and plasma exchange were not used. Follow-up at 9 months after transplant showed stable clinical status and no allograft rejection. In summary, the present case showed that when type A subgroup recipient has low level of anti-A₁ antibody and is receiving a kidney transplant from a blood type A donor, milder immunosuppressive preoperative therapy appears safe.

Key words : Blood group, Chronic kidney disease, Immunosuppression

Introduction

Type A subgroup is rare in Japan. In white people, the most common type A subgroup is A₂ (frequency, 20%), but Japanese people have a low frequency of A₂ antigen (0.2%) and antigens weaker than A₂ (0.021%).¹ Type A is classified by the degree of red blood cell agglutination by anti-A, anti-A₁, anti-AB, and anti-H antibodies, presence or absence of the anti-A1 antibody in the serum, and presence of A and H substances in saliva (Table 1).^2,3 Type A subgroups are characterized by decreased numbers of A antigen sites on the red blood cells. According to the density of the A antigens, type A subgroups are classified as A₁, A₂, A₃, Am, A_x, and A_el (Table 1).³

Kidney transplant with a type A₂ donor has been reported, but a type A subgroup recipient is very rare.⁴ We performed a kidney transplant from a type A donor to a type A subgroup recipient.

Case Report

A 65-year-old man presented for living-donor kidney transplant. He had a history of right nephrectomy because of a right kidney injury at age 10 years. Renal function gradually worsened and hemodialysis was started at age 38 years.

Blood group testing showed that his wife (kidney donor) was type A. The patient (recipient) was type A subgroup because reverse blood grouping showed a weak reaction with A₁ antigen. At a specialized blood typing center, blood group tests were performed including forward grouping, reverse grouping, saliva test, adsorption elution experiments, flow cytometry analysis, DNA analysis with polymerase chain reaction, and glycosyltransferase test. The recipient was diagnosed as type A subgroup between A_x and A_el because adsorption elution experiments and flow cytometry showed a few A antigens that were not detected on forward grouping, and DNA analysis was not consistent with A_el. The blood typing center recommended using type O blood for any transfusions because the recipient’s blood reacted with type A red blood cells at 37ºC.

The A antibody titer was 4(IgM) and 2(IgG). Therefore, we modified the protocol for ABO-incompatible kidney transplant in this center because the A antibody titer was positive (albeit low). Mycophenolate mofetil and prednisolone were started 3 weeks, and cyclosporine 2 weeks, before transplant. Rituximab (100 mg) was given once 2 weeks before transplant, and double filtration plasmapheresis and plasma exchange were not used.

After transplant, A antibody titer (< 2) and serum creatinine levels (114.9 μmol/L [1.3 mg/dL]) were low (Figure 1). A protocol biopsy at 3 months after transplant showed no polymorphonuclear cell accumulation in glomerular or peritubular capillaries and no complement fragment C4d staining in peritubular capillaries. Follow-up at 9 months after transplant showed stable clinical status and no allograft rejection.

Discussion

The present case was rare because the kidney transplant recipient was diagnosed as type A subgroup between A_x and A_el. This blood type diagnosis was made because adsorption elution experiments and flow cytometry analysis detected A antigens; these antigens were not detected with forward grouping, and DNA analysis was not consistent with A_el.

The frequency of A subgroups weaker than A₂ is rare in Japan (0.021%).¹ Furthermore, an A subgroup kidney transplant recipient is rare worldwide, with 1 study reporting 23 A₂ kidney transplant recipients from A₁ donors.5 In that study, the frequency of graft survival did not differ significantly between A₁ and A₂ recipients from A₁ donors, but none of the A₂ recipients had anti-A₁ antibodies.⁵ Anti-A1 anti-bodies occur as an alloantibody in the serum of 1% to 8% A₂ people.² Therefore, patients who have blood type A and anti-A₁ antibodies are rare. A literature search showed no previously reported kidney transplant from an A donor to an A subgroup recipient who had anti-A₁ antibodies.

The present patient was given a milder protocol for immunosuppressive preoperative therapy than typically used for ABO-incompatible kidney transplant, because the anti-A antibody was low. ABO-incompatible transplant is not rare in Japan, and the typical immunosuppressive protocol in this center before ABO-incompatible transplant includes mycophenolate mofetil, prednisolone, a calcineurin inhibitor (tacrolimus or cyclosporine), rituximab, and double filtration plasmapheresis or plasma exchange.⁶ The present patient received preoperative mycophenolate mofetil, prednisolone, and cyclosporine and had a safe transplant with only 1 rituximab treatment, without double filtration plasmapheresis or plasma exchange. The recipient avoided excessive immunosuppression, and had milder immunosuppressive therapy than usual, because he was diagnosed as type A subgroup between A_x and A_el. Therefore, when a type A subgroup recipient has a low level of anti-A₁ antibody and is receiving a kidney transplant from a type A donor, milder immunosuppressive preoperative therapy appears safe. In Japan, about 70% ABO-incompatible kidney transplants are performed safely when preoperative A or B antibody toters are < 32.⁷ Further study of type A subgroup recipients may enable the development of more suitable immuno-suppressive regimens.

References:

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