Blood group Lewis alloantibodies cause antibody-mediated rejection in renal transplant recipients.

Three patients with negative Lewis phenotypes who displayed anti-Lewis antibodies suffered severe kidney allograft dysfunction. One woman and two men (22-44 years) received ABO compatible kidney transplants with negative donor-recipient cross-match tests. Two patients had the phenotype Le(a-b-) with anti-Le(a) and anti-Le(b) complement binding antibodies. The third patient of phenotype Le(a+b-) developed anti-Lewis(b) antibody a few months after transplantation. One patient presented recurrence of worsened graft function from the day 6 to 4 months after transplantation; despite treatment there was not full recovery. The second patient had recurrences of acute graft dysfunction at 4 and 6 months after transplantation with nephrotic range proteinuria. The third patient showed progressive graft dysfunction at 7 months after transplantation. Biopsy specimens showed histological changes of antibody-mediated rejection. In the third patient, we observed fibrinoid necrosis and thrombosis of arterioles and glomerular capillaries. Immunofluorescence studies showed immunoglobulin IgG and IgM in glomerular capillaries and C4d and C3 on endothelial cells of peritubular capillaries. Posttransplantation cross-match tests with donor lymphocytes were negative. Anti-Lewis antibodies were observed during follow-up. All patients were treated with methylprednisolone boluses. In addition, one subject received antithymocyte globulin (ATG) and 1 received plasmapheresis. Two patients had moderate renal dysfunction (creatinine levels 1.8 and 1.9 mg/dL) after 8-17 months follow-up. The third patient lost her graft at 11 months after transplantation. Lewis antibodies may injure a renal allograft. C4d deposition and failure to show donor-specific anti-HLA antibodies suggested the participation of other antibodies.