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Targeted monitoring of donor-specific HLA antibodies following renal transplantation. 2011

K Almeshari, and A Pall, and A Chaballout, and H Elgamal, and H Almana, and F Alzayer, and N Abaalkhail, and M Altalhi
Department of Kidney and Pancreas Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. almeshari@kfshrc.edu.sa

Development of de novo donor-specific anti-HLA antibody (DSA) with antibody-mediated rejection (AMR) is the most important cause of renal allograft loss. Therefore, DSA monitoring might identify grafts susceptible to chronic humoral injury. However, implementing universal monitoring is logistically difficult, costly, and not yet supported by management guidelines, especially in patients with stable graft function. To gain further insight into humoral alloimmunity in transplant patients, we conducted a single center, retrospective study of AMR due to de novo DSA. We excluded patients without full characterization of the HLA specificities by single antigen solid phase immunoassay, and those where the clinical relevance of the DSA could not be determined. The clinical scenarios preceding AMR, HLA mismatches and alloantibody specificities, the histopathological phenotypes, and graft outcome were studied. We identified 44 renal transplant recipients with indication and protocol biopsies (44 biopsies for cause and 2 protocol biopsies), revealing 46 episodes of AMR and DSA (2 episodes in two patients). Most were late (more than 6 months after transplant). Suboptimal immunosuppression was an important prelude, usually due to non-adherence. DSA to DQ was prevalent and most biopsies were C4d positive. In all, 20 graft losses were attributed to AMR. From this study, we propose DSA monitoring in the patients with the following: (1) an episode of late (> 6 months) rejection; (2) history of non-adherence to immunosuppression; (3) immunosuppression minimization; (4) a class II loci (DR and DQ) mismatch transplant; or, (5) history of previous transplants. Close surveillance and protocol biopsies in those who develop de novo DSA is suggested.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011237 Predictive Value of Tests In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test. Negative Predictive Value,Positive Predictive Value,Predictive Value Of Test,Predictive Values Of Tests,Negative Predictive Values,Positive Predictive Values,Predictive Value, Negative,Predictive Value, Positive
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D003888 Desensitization, Immunologic Immunosuppression by the administration of increasing doses of antigen. Though the exact mechanism is not clear, the therapy results in an increase in serum levels of allergen-specific IMMUNOGLOBULIN G, suppression of specific IgE, and an increase in suppressor T-cell activity. Allergen Immunotherapy,Allergy Shots,Hyposensitization Therapy,Immunotherapy, Allergen,Venom Immunotherapy,Immunologic Desensitization,Therapy, Hyposensitization,Allergen Immunotherapies,Allergy Shot,Desensitizations, Immunologic,Hyposensitization Therapies,Immunologic Desensitizations,Immunotherapy, Venom,Shot, Allergy,Venom Immunotherapies
D005260 Female Females
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006648 Histocompatibility The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. HLA Incompatibility,Histoincompatibility,Human Leukocyte Antigen Incompatibility,Immunocompatibility,Tissue Compatibility,Compatibility, Tissue,HLA Incompatibilities,Histocompatibilities,Histoincompatibilities,Immunocompatibilities,Incompatibility, HLA,Tissue Compatibilities

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