Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation

Caro-Oleas, José Luis; González‐Escribano, María Francisca; González-Roncero, F.M.; Acevedo-Calado, Maria; Cabello-Chaves, Virginia; Gentil-Govantes, M.A.; Núñez‐Roldán, Antonio

doi:10.1093/ndt/gfr429

Cited by 93 publications

(67 citation statements)

References 21 publications

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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%

“…20 As was seen in the studies included in our primary analysis (group 1, negative flow crossmatch), all eight studies in group 2 (unknown flow crossmatch) were retrospective cohort studies in which the age of patients included with DSA-SPA was similar to the age of their comparative cohort without DSA in each individual study. [12][13][14][15][16][17][18][19] The types of donors included in these studies varied; three studies included only deceased-donor transplants, 14,16,18 one study included only living-donor transplants, 17 and four studies included both types of donors. 12,13,15 Induction regimens varied considerably across studies.…”

Section: Resultsmentioning

confidence: 99%

“…None of the studies included in group 2 consistently used a steroid-free maintenance regimen for their cohort. [12][13][14][15][16][17][18] The cohorts positive and negative for DSA-SPA within the individual studies received similar induction and maintenance regimens, and only a single study included patients with DSA-SPA who received peri-transplant desensitization. 16 The eight retrospective cohort studies in group 2 represented 1967 patients, of whom 306 (15.6%) were DSA-SPA positive (Table 1).…”

Section: Resultsmentioning

confidence: 99%

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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%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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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“…As a result, investigators can detect very low concentrations of HLAdirected antibodies. In the last decade, numerous reports have addressed the methodological aspects, clinical relevance, and standardization of the Luminex SP SA assay for the detection of antibodies [53,54,[95][96][97][98][99][100] . The results of these studies have significantly expanded our understanding of anti-HLA antibody biology and the mechanism of the interaction between antibodies with antigens.…”

Section: Luminexmentioning

confidence: 99%

“…It is generally accepted that de novo developed DSAs represent a risk factor for graft failure even at low concentrations. The early detection of DSAs considerably reduces the incidence of antibody-mediated rejection (AMR) and transplant glomerulopathy [23,[51][52][53][54][55][56][57][58] . A posttransplant antibody analysis is a part of the routine monitoring of recipients.…”

Section: Introductionmentioning

confidence: 99%

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Lobashevsky¹

2014

WJT

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Donor human leukocyte antigen (HLA)-specific antibodies (DSA) play an important role in solid organ transplantation. Preexisting IgG isotype DSA are considered a risk factor for antibody mediated rejection, graft failure or graft loss. The post-transplant development of DSA depends on multiple factors including immunogenicity of mismatched antigens, HLA class Ⅱ typing of the recipient, cytokine gene polymorphisms, and cellular immunoregulatory mechanisms. De novo developed antibodies require special attention because not all DSA have equal clinical significance. Therefore, it is important for transplant clinicians and transplant immunologists to accurately characterize DSA. In this review, the contemporary immunological techniques for detection and characterization of anti-HLA antibodies and their pitfalls are described.

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