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Volumn 16, Issue 4, 2011, Pages 398-403

Current methodologies for detecting sensitization to HLA antigens

Author keywords

antibodies; HLA; kidney transplant; sensitization; solid phase

Indexed keywords

HLA ANTIGEN; IMMUNOGLOBULIN G; PANEL REACTIVE ANTIBODY;

EID: 80051802723     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0b013e328348980a     Document Type: Review
Times cited : (24)

References (40)
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    • Tambur AR, Leventhal JR, Friedewald JJ, Ramon DS. The complexity of human leukocyte antigen (HLA)-DQ antibodies and its effect on virtual crossmatching. Transplantation 2010; 90:1117-1124. This study reports that a high percentage of patients with anti-DQ antibodies made antibodies against the polymorphic alpha or beta chains of HLA-DQ antigens. These complex antibodies are often a challenge in the virtual crossmatch.
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    • Gloor JM, Winters JL, Cornell LD, et al. Baseline donor-specific antibody levels and outcomes in positive crossmatch kidney transplantation. Am J Transplantation 2010; 10:582-589. This study used a combination of tests to show that the risk of antibody-mediated damage after transplant increased with the level of DSA present before transplantation. The data suggest that setting very low thresholds for DSA may prevent many transplants that would have good outcomes.
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    • The author points out that combinations of paired donation and desensitization -avoiding and/or overcoming DSA -provide the best options for patients with incompatible living donors
    • Montgomery RA. Renal transplantation across HLA and ABO antibody barriers: Integrating paired donation into desensitization protocols. Am J Transplant 2010; 10:449-457. The author points out that combinations of paired donation and desensitization -avoiding and/or overcoming DSA -provide the best options for patients with incompatible living donors.
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    • A study of the UNOS data 6 months following the change to calculated PRA and virtual cross-matching showed that virtual cross-matches based on solid-phase tests were very accurate and resulted in more transplants for broadly sensitized patients. Despite some remaining limitations to the solid-phase tests, they have proven beneficial for many sensitized patients
    • Cecka JM, Kucheryavaya AY, Reinsmoen NL, Leffell MS. Calculated PRA: Initial results show benefits for sensitized patients and a reduction in positive crossmatches. Am J Transplant 2010; 11:719-724. A study of the UNOS data 6 months following the change to calculated PRA and virtual cross-matching showed that virtual cross-matches based on solid-phase tests were very accurate and resulted in more transplants for broadly sensitized patients. Despite some remaining limitations to the solid-phase tests, they have proven beneficial for many sensitized patients.
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    • Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure
    • This multicenter study reports that nearly 60% of patients with new-onset graft dysfunction 5 years after transplantation had DSA or C4d in biopsies and that these patients' subsequent graft survival was significantly worse than those without evidence of antibody-mediated injury. New DSA long after transplant was a major cause of late graft failure
    • Gaston RS, Cecka JM, Kasiske BL, et al. Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation 2010; 90:68-74. This multicenter study reports that nearly 60% of patients with new-onset graft dysfunction 5 years after transplantation had DSA or C4d in biopsies and that these patients' subsequent graft survival was significantly worse than those without evidence of antibody-mediated injury. New DSA long after transplant was a major cause of late graft failure.
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    • A registry study of more than 3000 recipients with antibody testing performed centrally suggests DSA detected only by the single antigen bead test do not increase graft losses during the first 3 years and should not be used to exclude patients from transplantation
    • Süsal C, Ovens J, Mahmoud K, et al. No Association of kidney graft loss with human leukocyte antigen antibodies detected exclusively by sensitive luminex single-antigen testing: A collaborative transplant study report. Transplantation 2011; 91:883-887. A registry study of more than 3000 recipients with antibody testing performed centrally suggests DSA detected only by the single antigen bead test do not increase graft losses during the first 3 years and should not be used to exclude patients from transplantation.
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    • Lefaucheur C, Loupy A, Hill GS, et al. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol 2010; 21:1398-1406. These authors report that even very low levels of DSA detected only in historical but not current serum samples can affect transplant outcome.
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    • Tait BD, Hudson F, Brewin G, et al. Solid phase HLA antibody detection technology-challenges in interpretation. Tissue Antigens 2010; 76:87-95. This is a very comprehensive literature review highlighting the development of solid-phase tests for HLA antibody and outlining many of the challenges in interpreting results (66 references including historical).
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    • Taylor CJ, Kosmopoliaptis V, Sharples LD, et al. Ten-year experience of selective omission of the pretransplant crossmatch test in deceased donor kidney transplantation. Transplantation 2010; 89:185-193. These results suggest that careful monitoring of patients for anti-HLA antibodies and for potential sensitizing events before transplantation provides the confidence to forgo final crossmatches for unsensitized patients.
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    • Taylor, C.J.1    Kosmopoliaptis, V.2    Sharples, L.D.3
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    • Interpretation of positive flow cytometric crossmatch in the era of the single-antigen bead assay
    • DSA detected only by solid-phase tests and not by a flow cytometry crossmatch did not affect short-term graft outcomes (1 year)
    • Couzi L, Araujo C, Guidicelli G, et al. Interpretation of positive flow cytometric crossmatch in the era of the single-antigen bead assay. Transplantation 2011; 91:527-535. DSA detected only by solid-phase tests and not by a flow cytometry crossmatch did not affect short-term graft outcomes (1 year).
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    • The use of multiple tests to assess the relevance of DSA is an important strategy. The authors use 'limited exclusion of donors with a high likelihood of positive crossmatch' rather than excluding those with any possibility of a positive crossmatch
    • Morris GP, Phelan DL, Jendrisak MD, Mohanakumar T. Virtual crossmatch by identification of donor-specific antihuman leukocyte antigen antibodies by solid-phase immunoassay: A 30-month analysis in living donor kidney transplantation. Hum Immunol 2010; 71:268-273. The use of multiple tests to assess the relevance of DSA is an important strategy. The authors use 'limited exclusion of donors with a high likelihood of positive crossmatch' rather than excluding those with any possibility of a positive crossmatch.
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    • This study used proficiency test samples which may be selected to include strong antibodies and may not reflect the spectrum of patient samples that could be encountered
    • Batal I, Zeevi A, Lunz JG 3rd, et al. Antihuman leukocyte antigen-specific antibody strength determined by complement-dependent or solid-phase assays can predict positive donor-specific crossmatches. Arch Pathol Lab Med 2010; 134:1534-1540. This study used proficiency test samples which may be selected to include strong antibodies and may not reflect the spectrum of patient samples that could be encountered.
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    • Riethmüller S, Ferrari-Lacraz S, Müller MK, et al. Donor-specific antibody levels and three generations of crossmatches to predict antibodymediated rejection in kidney transplantation. Transplantation 2010; 90: 160-167.
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    • Subclinical rejection in stable positive crossmatch kidney transplant patients: Incidence and correlations
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    • Kraus, E.S.1    Parekh, R.S.2    Oberai, P.3
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    • 77953812538 scopus 로고    scopus 로고
    • Subtypes of immunoglobulin (Ig)-G antibodies against donor class II HLA and cross-match results in three kidney transplant candidates
    • Lobashevsky A, Rosner K, Goggins W, Higgins N. Subtypes of immunoglobulin (Ig)-G antibodies against donor class II HLA and cross-match results in three kidney transplant candidates. Transpl Immunol 2010; 23:81-85.
    • (2010) Transpl Immunol , vol.23 , pp. 81-85
    • Lobashevsky, A.1    Rosner, K.2    Goggins, W.3    Higgins, N.4
  • 38
    • 77954089708 scopus 로고    scopus 로고
    • C4d-fixing capability of low-level donor-specific HLA antibodies is not predictive for early antibody-mediated rejection
    • These authors had developed this test and showed correlation with C4d deposition in biopsies, but that relationship did not hold true for weaker antibodies
    • Hönger G, Wahrmann M, Amico P, et al. C4d-fixing capability of low-level donor-specific HLA antibodies is not predictive for early antibody-mediated rejection. Transplantation 2010; 89:1471-1475. These authors had developed this test and showed correlation with C4d deposition in biopsies, but that relationship did not hold true for weaker antibodies.
    • (2010) Transplantation , vol.89 , pp. 1471-1475
    • Hönger, G.1    Wahrmann, M.2    Amico, P.3
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    • C4d binding correlated with strong HLA antibodies involved in graft failure
    • This study raises some question about the complement fixation tests. Do they just eliminate detection of weaker antibodies?
    • Mizutani K, Gotoh M. C4d binding correlated with strong HLA antibodies involved in graft failure. Transplant Proc 2010; 42:4021-4025. This study raises some question about the complement fixation tests. Do they just eliminate detection of weaker antibodies?
    • (2010) Transplant Proc , vol.42 , pp. 4021-4025
    • Mizutani, K.1    Gotoh, M.2
  • 40
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    • C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation
    • Measuring functionality of DSA is an approach that is generating interest, but needs study. This test has been made commercially available
    • Yabu JM, Higgins JP, Chen G, et al. C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation. Transplantation 2011; 91:342-347. Measuring functionality of DSA is an approach that is generating interest, but needs study. This test has been made commercially available.
    • (2011) Transplantation , vol.91 , pp. 342-347
    • Yabu, J.M.1    Higgins, J.P.2    Chen, G.3


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