Clinical Relevance of Pretransplant Donor-Specific HLA Antibodies Detected by Single-Antigen Flow-Beads

Amico, Patrizia; Hönger, Gideon; Mayr, Michael; Steiger, Jürg; Hopfer, Helmut; Schaub, Stefan

doi:10.1097/tp.0b013e3181a5e034

Cited by 237 publications

(221 citation statements)

References 26 publications

(29 reference statements)

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“…[12][13][14][15][16][17][18][19][20] These studies were excluded from our primary analysis. A quantitative analysis of this cohort (group 2) was limited to eight studies because adequate data could not be extracted from one of the studies identified for inclusion in this analysis.…”

Section: Resultsmentioning

confidence: 99%

Donor-Specific Antibodies Adversely Affect Kidney Allograft Outcomes

Mohan

Palanisamy

Tsapepas

et al. 2012

Journal of the American Society of Nephrology

241

176

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The effect of low titers of donor-specific antibodies (DSAs) detected only by sensitive solid-phase assays (SPAs) on renal transplant outcomes is unclear. We report the results of a systematic review and metaanalysis of rejection rates and graft outcomes for renal transplant recipients with such preformed DSAs, defined by positive results on SPA but negative complement-dependent cytotoxicity and flow cytometry crossmatch results. Our search identified seven retrospective cohort studies comprising a total of 1119 patients, including 145 with isolated DSA-SPA. Together, these studies suggest that the presence of DSA-SPA, despite a negative flow cytometry crossmatch result, nearly doubles the risk for antibody-mediated rejection (relative risk [RR], 1.98; 95% confidence interval [CI], 1.36-2.89; P,0.001) and increases the risk for graft failure by 76% (RR, 1.76; 95% CI, 1.13-2.74; P=0.01). These results suggest that donor selection should consider the presence of antibodies in the recipient, identified by the SPA, even in the presence of a negative flow cytometry crossmatch result. In 1969, Patel and Terasaki published their landmark study that definitively established the detrimental effect of preformed donor-specific antibodies (DSAs) detected by complement-dependent cytotoxicity (CDC) crossmatch on short-term allograft survival, but they noted the limited sensitivity of the technique in the detection of preformed DSAs. 1 Since that time, technological advances have led to increasingly more sensitive tests for the detection of anti-HLA DSAs, including flow cytometry crossmatch and the more recent solid-phase assays (SPAs), such as Luminex. 2,3 The clinical significance of DSAs detected by sensitive SPA remains unclear, with disparate findings being reported in the literature. 4 Further, the clinical utility of these tests, particularly for prognostication or modifying immunosuppressive therapy, when used individually or in some sequential manner remains unclear. Our aim was to perform a systematic review and meta-analysis of published reports of rejection rates and graft outcomes among renal transplant recipients with preformed DSA at levels detectable only by SPA but not by CDC or flow crossmatch. RESULTSWe ultimately identified seven studies that met our inclusion criteria for the primary quantitative analysis (group 1). [5][6][7][8][9][10][11] All seven studies were retrospective cohort studies; three were from the United States and four from Europe. Our ability to compare

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Section: Resultsmentioning

confidence: 99%

Donor-Specific Antibodies Adversely Affect Kidney Allograft Outcomes

Mohan

Palanisamy

Tsapepas

et al. 2012

Journal of the American Society of Nephrology

241

176

View full text Add to dashboard Cite

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“…Therefore, in pretransplant period, determination of clinically relevant alloantibodies in sensitized patients and monitoring of antibody level during desensitization treatment would be needed. But in posttransplant period, although there are significant amount of evidences for the causal effect of DSA in graft rejection, the uniform consensus or guidelines for immune monitoring is hard to be set up partly because the lack of validated therapy once DSA are detected in a clinically and pathologically stable patient and vice versa (21)(22)(23)(24) and partly because the lack of data whether low level of DSA or anti-allelic DSA cause graft dysfunction (25,26) The study was performed by questionnaire surveys through emailing. The questionnaires were developed in two (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Results of Questionnaire Survey of Current Immune Monitoring Practice of Transplant Clinicians and Clinical Pathologists in Korea: Basis for Establishment of Harmonized Immune Monitoring Guidelines

Kang

Choi

Park

et al. 2018

Korean J Transplant

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Detection of significant alloimmune response, which affects graft function and survival by effective immune monitoring, is critical for treatment decision making. However, there is no consensus regarding immune monitoring (IM) for kidney transplantation (flow KT) in Korea. The IM protocol may be affected by the level of immunological risk, the methods of desensitization and the availabilities of resources such as laboratory support and cost of tests. Questionnaire surveys designed to identify the current practi- Until now, the immunological monitoring of alloimmune responses are focused on the detection of rejection events in practice than detection of adverse immune activity which might be preceded clinically or pathologically evident rejection signs. It might be rather because there were no reliable and well validated laboratory methods to be applicable.However, luminex bead technologies used for the detection of antibodies in antigen, allele or epitope levels for HLA(7-9) and non-HLA systems(15), and molecular technologies to detect transcript signatures of diverse immunologic changes are broadening our choice of tests(16-18).And it is continuously reflected on diagnostic criteria such as Banff criteria (19,20). However, the diagnostic criteria does not specify the practical way of immune monitoring in real world, so, there is no standardized guidelines and is Immune monitoring protocolsAbout 28% (9/32) of clinicians from 6 institutes (6/25, 24%) are performing protocol biopsies at various time points and the number of biopsy depending on the level of immunological risks (Fig. 3). When higher the risk, more frequent biopsies are being performed within posttransplant 12 weeks (Fig. 4). Clinicians are applying different combinations of HLA antibody tests in different time points and also depending on the level of immunological risks. Antibody monitoring is being performed frequently at posttransplant 3∼4 weeks, 24 weeks and yearly (Fig. 5). Antibody screening test is used for low risk patients, however for high risk patients, HLA antibody phenotyping or SAB identification tests are used more frequently (Fig. 6). The suggested time points of HLA antibody monitoring test in patients waiting for kidney transplantation was questioned regardless of current protocols (Fig. 7). Twenty-four out of 26 (92%) respondents answered that the presence of HLA antibody needed to be checked at registration in KONOS regardless of immunological risk levels, and for living donor kidney transplant (LDKT) candidates, it is suggested to do within pre-transplant 4 weeks. Twelve (46%) respondents replied that the monitoring of HLA antibody is necessary if the patients had recent transfusion or pregnancy episodes.As on-demand test when the rejection is suspected clinically, 70% (22/32) of respondents answered proceeding to HLA antibody test but 15% (5/32) answered to do HLA antibody test when the pathologic finding of AMR in biopsy identified (Fig. 8).2. sponses needs to be cautious because it may be rather because not all the instit...

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“…In one study, 30 out of the 67 patients who had anti-HLA DSA did not have a clinical/subclinical antibody mediated rejection [28]. Five-year death censored graft survival among this group was similar to the transplant patients without anti-HLA DSA.…”

Section: Significance Of Donor Specific Antibodiesmentioning

confidence: 96%

“…In one study that investigated DSA in over 400 transplant recipients, those with preformed anti-HLA DSA had inferior graft survival at 8 years as compared with those with no preformed DSA (93% vs. 61%) [27]. Another study investigated pre-transplant DSA in 334 patients and found a higher incidence of clinical/subclinical antibody mediated rejection in those with DSA (55% vs. 6%) [28]. The strength of the DSA as measured by MFI may also play a role in the development of antibody mediated rejection [27].…”

Section: Significance Of Donor Specific Antibodiesmentioning

confidence: 99%