The significance of B-cell crossmatching in kidney transplantation is controversial. Recipients (n = 471) transplanted in a single centre from 1987 to 2005 with complete T- and B-cell crossmatch records were studied. Sera from 83 patients transplanted across a positive B-cell crossmatch, with concomitant negative T-cell crossmatch (T-B+) on either current and/or peak sera were studied using Luminex to determine presence of donor-specific antibodies (DSA). Clinical outcomes of T-B+ patients were compared with 386 T-B- patients. T-B+ predicted vascular (p = 0.01), but not cellular (p = 0.82) or glomerular (p = 0.14) rejection. IgG HLA DSA were found in 33% (n = 27) of the T-B+ patients and were associated with higher risk of any (p = 0.047), vascular (p = 0.01) or glomerular (p < 0.001) rejection at 6 months. Of 27 patients with DSA, 18/21 (86%) were the complement-fixing IgG(1) and/or IgG(3) subclass antibodies. DSA imposed a statistically significant higher risk of graft loss 5 years posttransplant (1.8 [1.0-3.3], p = 0.045). This study showed that only one-third of positive B-cell crossmatch (BXM) was caused by DSA and was associated with late graft loss. Thus, using BXM to preclude kidney transplantation may potentially disadvantage >60% of patients in whom BXM is not indicative of the presence of DSA.
SummaryThere are no accepted methods to predict the development of platelet transfusion refractoriness (PTR) due to human leucocyte antigen (HLA)-alloimmunization. Hence, matched platelets are usually given only to patients demonstrating PTR, necessarily resulting in some ineffective random donor platelets (RDPLT) transfusions. To assess its utility in predicting PTR, we retrospectively tested samples from 387 patients receiving chemotherapy for acute leukaemia or autologous transplantation using a micro-bead flow cytometry assay. The average of the mean fluorescence intensities (avgMFI) of the class I beads in the screening assay was correlated with outcomes of RDPLT transfusions during a 2 week period. Antibodies were detected in 57 patients; 66 developed PTR, of whom 28 were alloimmunized. avgMFI usefully predicted the development of PTR (area under the receiver operating curve 0Á87, 95% confidence interval: 0Á77-0Á96). A logistic regression model estimated the probability of PTR to be >90% when avgMFI >5440. These results indicate that micro-bead flow cytometry assays could inform a risk-adapted strategy for managing thrombocytopaenic HLA allo-immunized patients.
Summary
Desensitization protocols reduce donor‐specific anti‐HLA antibodies (DSA) and enable renal transplantation in patients with a positive complement‐dependent cytotoxic cross‐match (CDC‐CXM). The effect of this treatment on protective antibody and immunoglobulin levels is unknown. Thirteen patients with end‐stage renal disease, DSA and positive CDC‐CXM underwent desensitization. Sera collected pre‐ and post‐transplantation were analysed for anti‐tetanus and anti‐pneumococcal antibodies, total immunoglobulin (Ig) levels and IgG subclasses and were compared to healthy controls and contemporaneous renal transplant recipients treated with standard immunosuppression alone. Ten patients developed negative CDC‐CXM and enzyme‐linked immunosorbent assay (ELISA) and underwent successful transplantation. Eight recipients achieved good graft function without antibody‐mediated or late rejection, BK virus or cytomegalovirus infection. One patient had primary non‐function due to recurrent oxalosis, and one patient with immediate graft function died from septicaemia. Seven recipients required post‐operative transfusion and three developed septicaemia. DSA remained negative by ELISA at 12 months, but were detectable by Luminex®. Anti‐tetanus and anti‐pneumococcal antibodies, total Ig and IgG subclasses were below the normal range but comparable to levels in renal transplant recipients who had not undergone desensitization. Desensitization protocols effectively reduce DSA and allow successful transplantation. Post‐operative bleeding and short‐term infectious risk is increased. Protective antibody and serum immunoglobulin levels are relatively preserved.
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