De novo HLA donor specific antibodies (DSA) following transplantation are associated with alloimmune injury and allograft failure. Blood transfusions are allogeneic, and when given posttransplant (PTBT) they may independently increase the risk of HLA antibody development. This study aims to analyse the development of HLA transfusion specific antibodies (TSA) to blood donors of transfusions given post-transplant and examine the impact on clinical outcomes. 244 blood donors of transfusions received by 86 transplant patients (46 who developed a DSA post transfusion and 40 who remained DSA negative) were HLA typed. De novo TSA developed against 150/244(61.5%) blood donors. In 70/150(46.7%) cases the TSA was of shared HLA antibody specificity with a DSA response in the recipient (DSA+=TSA+). This occurred when there was a greater overall HLA match between the blood and transplant donor. DSA+=TSA+ patients had increased risk of allograft failure [p=0•0025] and AMR [p=0•02] compared with the DSA+≠TSA+ patients. To conclude, PTBT may elicit de novo HLA antibodies. Enhanced HLA matching between the blood and transplant donor is more likely to result in a DSA and TSA of shared antibody specificities. Transfusion avoidance or the use of HLA matched or selected blood may reduce this risk and improve outcomes.
SUMMARYStudies in humans suggest that allo-immunization induces CC-chemokines, CD8-suppressor factors (SF) and anti-HIV immunity. Here we report that allo-immunization with unmatched leucocytes from partners of women with recurrent spontaneous abortion elicits specific antibodies to the CCR5 receptor. Such antibodies inhibit replication of M-tropic HIV-1 (R5) and MIP-1b-mediated chemotaxis. These CCR5 antibodies were also found in the sera of multiparous women that were naturally immunized by semi-allogeneic fetal antigens. The specificity of these antibodies was demonstrated by adsorption with CCR5 transfected HEK-293 cells, a baculovirus CCR5 preparation and a peptide of the 2nd extra-cellular loop of CCR5. Allo-immunization also stimulated increased concentrations of the CXC chemokine, SDF-1a and CD8-SF that inhibit T-tropic HIV-1 (X4) replication. We suggest that alloimmunization may elicit (a) CC chemokines, CCR5 antibodies and CD8-SF that inhibit M-tropic HIV-1 infection and (b) the CXC chemokine SDF-1a and CD8-SF that inhibit T-tropic HIV-1 infection.
Recent evidence suggests that alloantibody may play an aetiological role in the pathogenesis of membranous glomerulopathy in native kidneys. There is an increased awareness of the significance of alloantibody on renal transplant outcome, particularly with the development of more sensitive assays. We describe a kidney transplant patient who developed de novo membranous glomerulopathy (DNMG) with heavy proteinuria in the context of a donor-specific alloantibody (DSA) directed against HLA DQ7. Proteinuria resolved and kidney function stabilized following treatment with mycophenolate mofetil and an angiotensin receptor blocker. The titre of the DSA fell in parallel with resolution of the proteinuria. This is the first reported case of DNMG after kidney transplantation clearly associated with a DSA. We hypothesize that de novo membranous glomerulopathy may be an atypical manifestation of acute antibody-mediated damage. Cases of DNMG should be screened for alloantibody and the presence of alloantibody may influence the choice of therapy.
Proteinuria is associated with DSA detection and is likely to be an important factor that determines rapid GFR decline and earlier graft failure in patients developing de novo HLA antibodies.
These results suggest that PRA-STAT is a useful technique for the detection of both HLA class I- and class II-specific antibodies, rather than only class I-specific antibodies as previously described.
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