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Review
. 2017 Dec 8;2017(1):645-650.
doi: 10.1182/asheducation-2017.1.645.

HLA donor-specific antibodies in allogeneic hematopoietic stem cell transplantation: challenges and opportunities

Douglas E Gladstone  1 , Maria P Bettinotti  2
Affiliations
Review

HLA donor-specific antibodies in allogeneic hematopoietic stem cell transplantation: challenges and opportunities

Douglas E Gladstone et al. Hematology Am Soc Hematol Educ Program. .

Abstract

Allogenic hematopoietic stem cell recipients may have preformed antibodies directed against foreign HLA antigens. The use of partially HLA-mismatched allogeneic hematopoietic stem cell donors allows for the possibility of the presence of circulating HLA donor-specific antibodies (DSAs) in the recipient. The presence of DSAs at the time of stem cell infusion increases the risk of primary graft failure. More recently developed technology using solid phase immunoassays (SPIs) with fluorochrome-conjugated beads has greatly improved the ability to detect and classify DSAs. When used in combination with the classic lymphocytotoxic complement-dependent and flow cytometric crossmatch tests, SPIs help provide DSA strength assessment. Parous females frequently harbor DSAs. DSAs tend to be of higher intensity when directed against haploidentical first-degree relatives. DSA assessment requires frequent monitoring as their relative strength can change over time. Although the criteria that constitutes a prohibitive DSA is unknown, desensitization techniques can result in engraftment rates as experienced in fully HLA-matched allogeneic blood or marrow transplantation recipients.

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Conflict of interest statement

Conflict-of-interest disclosure: D.E.G. declares no completing financial interests. M.P.B. has been affiliated with the Speakers Bureau for One Lambda, Inc.

Figures

Figure 1.
Figure 1.
Luminex HLA antibody assay principle. The principle of the Luminex-based HLA antibody assay is depicted. (1) Bead coated with HLA molecules. Up to 100 different sets of color-coded beads, each bearing 1 or several HLA types can be tested simultaneously. Each bead set is internally dyed with differing ratios of 2 fluorochromes resulting in a unique signal. (2) After incubation with the test serum, the HLA antibody, if present, binds to the appropriate HLA molecule. Non-HLA antibodies are discarded after washing. (3) The bound HLA antibody is detected by a phycoerythrin-conjugated secondary antibody specific for human IgG. (4) The beads are analyzed on a dual-laser flow-based detection instrument. The red laser classifies the bead and determines the HLA molecule that is being detected. The green laser determines the magnitude of the phycoerythrin-derived signal, which is proportional to the amount of HLA antibody bound.
Figure 2.
Figure 2.
Luminex bead characteristics. The 3 formats of Luminex beads.
Figure 3.
Figure 3.
The number of exchanges was determined by the baseline strength of DSAs and rebound.
See this image and copyright information in PMC

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