Judith E Worthington

The Bracton Centre, Oxleas NHS Trust, Дартфорде, England, United Kingdom

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Publications (9)20.05 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We carried out a retrospective study of C4d staining in paraffin sections from renal transplant biopsies to determine the association between C4d staining, donor-specific antibodies (DSA), histological features, and graft outcome. We studied 92 patients who had been biopsied for graft dysfunction. Biopsies were classified using Banff 97 criteria and features suggestive of antibody-mediated rejection were noted. Paraffin sections were stained with a polyclonal antibody using an immunoperoxidase technique. The presence of DSA in concurrent sera was determined by enzyme-linked immunosorbent assay and clinical data were reviewed. Of the 92 cases, 15% showed diffuse and 24% showed focal C4d positivity. The grafts failed in 36% of the diffuse (P<0.025), 23% of the focal, and 7% of the negative group at between one month and 15 years posttransplantation. Only patients in the group with diffuse C4d positivity had concurrent DSA (five cases, P<0.001). Of the five DSA-positive patients, three had type II acute rejection and two of these transplants subsequently failed. The remaining two had chronic allograft nephropathy with features of alloimmune injury. Only two of the nine DSA-negative/C4d-positive transplants had failed at the time of writing, in one case due to recurrent disease. We demonstrated a significant association between diffuse C4d staining, production of DSA, and graft failure. Although the concurrent detection of DSA and C4d positivity is uncommon in our patients, these results indicate that outcome in this group is poor and they may benefit from therapies directed at the humoral response.
    Transplantation 02/2007; 83(4):398-403. · 3.78 Impact Factor
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    ABSTRACT: The post-transplantation production of antibodies directed against donor HLA class I and class II mismatches has been shown to be associated with transplant rejection. Recipient sensitization against donor HLA plays a key role in transplant rejection; this risk is best minimized by efficient pre-transplant antibody detection and definition, effective pre-allocation cross-matching, and minimization of HLA mismatches between donor and recipient. The term "PRA" is of little value. Identification of the HLA specificity to which an antibody is directed is essential and now possible using contemporary methodology. It is now recognized that antibody-mediated rejection should be diagnosed on the basis of allograft dysfunction, characteristic features of histology, C4d immunohistology, and the presence of donor-specific antibodies. HLA-DP is becoming recognized as a "transplantation antigen." For the future, the repertoire of a histocompatibility laboratory must expand to include typing organ transplant recipients and donors for HLA-DP and also the definition of antibodies to DP. Antibodies to non-HLA targets should be an important consideration when assessing factors that influence transplant outcome.
    Clinical transplants 02/2006;
  • Human Immunology - HUM IMMUNOL. 01/2005; 66(8):85-85.
  • Naheed Khan, Amanda J Robson, Judith E Worthington, Susan Martin
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    ABSTRACT: We have developed a flow cytometry-based screening method using FlowPRA (One Lambda) human leukocyte antigen (HLA) class I panel beads and FlowPRA (One Lambda) HLA class I specificity beads for the detection and definition of immunoglobulin (Ig)M HLA-specific antibodies in the presence of IgM autoantibodies. Forty-six autoantibody-positive patients who were on the waiting list for a renal transplant (56 sera) were tested in parallel with FlowPRA (One Lambda) HLA class I beads and FlowPRA (One Lambda) control beads. Sera that were positive for IgM HLA class I antibodies were subsequently tested with FlowPRA HLA class I specificity beads to determine the HLA specificities. Thirteen of the 46 patients were positive for IgM HLA class I-specific antibodies. Eleven of the 13 had previous failed transplants and 2 were awaiting a primary transplant. For 9 of the 13 positive patients, IgM HLA class I specificities were defined. We have demonstrated the presence of IgM HLA-specific antibodies in patients with IgM autoantibodies. This study demonstrates the value of FlowPRA HLA class I panel and specificity beads for the detection and definition of IgM HLA class I-specific antibodies.
    Human Immunology 07/2003; 64(6):593-9. · 2.30 Impact Factor
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    ABSTRACT: This study aimed to determine whether the production, in renal transplant recipients, of antibodies directed against donor HLA mismatches is predictive of transplant failure. The failure study group comprised 112 adult recipients of primary renal transplants who had re-entered the transplant waiting list after failure of the first graft. A control group of 123 recipients with functioning transplants was selected from transplantations performed during the same time period, in which patients had equivalent HLA matching and immunosuppression and a minimum of 5 years of follow-up. Sera taken before transplantation and at 1, 3, and 6 months and annually after transplantation were tested by enzyme-linked immunoabsorbent assay (ELISA) for the presence of HLA class I- and class II-specific antibodies. Antibody specificity was defined by a combination of cytotoxicity, ELISA, and flow cytometry techniques to determine whether the antibodies were directed against donor mismatches. All recipients were negative for donor HLA-specific antibodies before transplantation. After transplantation, 57 (50.9%) of the 112 patients in the failure group produced donor HLA-specific antibodies compared with 2 (1.6%) of the 123 controls (P<0.0001; odds ratio [OR]=64.98; confidence interval [CI], 14.78-399.51). For 60% of the donor-specific antibody-positive patients, antibodies were detected before transplant failure. In 17 cases, these were class I specific; in 14 cases, class II specific; and in 3 cases, specific for both class I and II. This study has demonstrated that the production of posttransplantation antibodies directed against donor HLA-A, -B, -Cw, -DR, and -DQ mismatches are all strongly predictive of transplant failure.
    Transplantation 04/2003; 75(7):1034-40. · 3.78 Impact Factor
  • J E Worthington, A J Robson, S Sheldon, A Langton, S Martin
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    ABSTRACT: LATM, Quikscreen (QS), and B-Screen (QSB) are ELISA-based tests for the detection of HLA specific antibodies. FlowPRA beads are microparticles coated with HLA antigens for the detection of HLA specific antibodies by flow cytometry. The aim of this study was to evaluate the sensitivity and specificity of the LATM, QS, QSB, and FlowPRA screening tests. One hundred sixty-three sera from renal transplant patients were tested using LATM, FlowPRA, QS, and QSB. Discrepant results were further investigated using complement dependent cytotoxicity, QuikID, and PRA-STAT. When QS was compared with LATMI and FlowPRAI for the detection of HLA class I specific antibodies the overall concordance was 82.8% with no particular specificity missed by any one test. Comparing QSB with LATMII and FlowPRAII, for the detection of HLA class II specific antibodies, there was 90.7% concordance. Although the overall concordance was better for class II specific antibodies, QSB failed to detect antibodies to HLA-DQ in a number of samples from different patients. Of the methods tested, flow cytometry using FlowPRA beads appeared to be the most sensitive and specific, missing the least number of specificities. However, the ELISA methods offer the advantage of being more suitable for testing large numbers of samples in a more time- and cost-effective manner.
    Human Immunology 11/2001; 62(10):1178-84. · 2.30 Impact Factor
  • J E Worthington, S Martin, P A Dyer, R W Johnson
    Transplantation Proceedings 02/2001; 33(1-2):475-6. · 0.95 Impact Factor
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    J E Worthington, A Langton, H Liggett, A J Robson, S Martin
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    ABSTRACT: Conventional testing for HLA-specific antibodies employs complement-dependent cytotoxicity (CDC) which is labour intensive and dependent on a supply of viable lymphocytes. Our strategy to minimise CDC screening is initially to screen sera by ELISA (Quikscreen) to detect HLA Class I-specific antibodies. Negative sera are then screened by flow cytometry (FCS) using lymphoblastoid cell line pools to detect HLA Class II-specific antibodies. Only Quikscreen- or FCS-positive sera are then tested by CDC and, when indicated, with an ELISA kit (PRA-STAT) for specificity definition. Of 3680 sera, 886 (24.1%) were Quikscreen positive. Of the 2794 Quikscreen-negative sera, 374 (13.4%) were FCS positive. Therefore, only 1265 of the 3680 (34.3%) sera contained HLA-specific antibodies requiring specificity definition. This novel screening strategy has significantly reduced the CDC workload of the laboratory whilst enabling the detection of additional HLA-specific antibodies.
    Transplant International 02/1998; 11 Suppl 1:S372-6. · 3.16 Impact Factor
  • Source
    J E Worthington, A A Thomas, P A Dyer, S Martin
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    ABSTRACT: The aim was to investigate the correlation between renal transplant outcome and the presence of HLA-specific antibodies detected using the ELISA kit PRA-STAT as compared with complement-dependent cytotoxicity (CDC). 295 sera from 95 renal transplant recipients (99 transplants) were investigated for the presence of HLA-specific antibodies using both PRA-STAT and CDC. The patients were divided into group I (49 transplants failed within 1 month) and group II (50 successful transplants). The concordance between PRA-STAT and CDC for the detection of HLA class I-specific antibodies was 87.8% (259 of 295). For 19 sera, antibodies were detected only by PRA-STAT; for 17 sera, antibodies were detected only by CDC. No donor-specific antibodies were detected by either technique for patients in group II. For four group I patients (six sera), donor-specific IgG antibodies were detected only by PRA-STAT (one before, three after transplant) and all four transplants failed. For five other group I patients (six sera), donor HLA-specific antibodies were detected only by CDC (one before, four after transplant) and all five transplants failed. The antibodies detected before transplant by CDC were shown to be IgM alloantibodies. This study showed that PRA-STAT could detect HLA-specific IgG antibodies relevant to transplant outcome that were not detected by CDC. However, it could not detect IgM alloantibodies that were also shown to be important. PRA-STAT is therefore a useful addition to a histocompatibility laboratory's screening repertoire only when used in conjunction with other techniques.
    Transplantation 02/1998; 65(1):121-5. · 3.78 Impact Factor