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Journal of Immunological Methods 369 (2011) 1–21

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Journal of Immunological Methods
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j i m

Review

Histocompatibility testing after fifty years of transplantation
Hooi Sian Eng, Mary S. Leffell ⁎
Department of Medicine, the Johns Hopkins University School of Medicine,USA

a r t i c l e

i n f o

a b s t r a c t
Histocompatibility testing has been used in support of solid organ and hematopoietic stem cell transplantation for over fifty years and transplantation has clearly served as a major stimulus for interest in the human major histocompatibility complex, the HLA system. Until the 1990s, typing and definition of antibodies to HLA antigens was performedprimarily by serologic techniques using cell-based assays. Two major technological advances have greatly increased knowledge of HLA alleles and HLA-specific antibodies, namely the introduction of DNA based molecular typing and solid phase immunoassays using purified HLA antigens as targets. By virtue of these advances, the number of recognized HLA alleles has increased from a few hundred togreater than 6000 and definition of the specificities of antibodies to HLA antigens is now possible at the level of individual epitopes. The technological advancements have also raised new challenges. The vast and ever increasing number of HLA alleles has resulted in ambiguities in allele assignments which confound matching for hematopoietic stem cell transplants. Similarly, the ability to detectextremely low levels of HLA-specific antibodies has raised questions about whether such low levels are clinically relevant. Next generation DNA sequencing methods likely will offer the solution to many of the HLA typing ambiguities and future studies on the nature of both HLA and non-HLA-specific antibodies will clarify their impact on transplant outcomes. © 2011 Published by Elsevier B.V.

Articlehistory: Received 16 October 2010 Received in revised form 31 March 2011 Accepted 11 April 2011 Available online 17 April 2011 Keywords: HLA antigens HLA antibodies Histocompatibility Immunogenetics Solid organ transplantation Hematopoietic cell transplantation

Contents 1. 2. Introduction and background . . . . . . . . . . . . . . . . HLA typing . . . . . . . . . . . . . . . . . . . . . . . . .2.1. Cell-based serologic assays . . . . . . . . . . . . . . 2.2. Mixed lymphocyte culture . . . . . . . . . . . . . . 2.3. DNA based molecular techniques . . . . . . . . . . . 2.4. Nomenclature . . . . . . . . . . . . . . . . . . . . 2.5. Application of HLA Typing in Solid Organ Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3 5 6 6 8 9

Abbreviations: AMR, antibody mediated rejection;CDC, complement dependent cytotoxicity; CFSE, carboxyfluorescein succinimidyl ester; CPRA, calculated panel reactive antibody; CREG, cross-reactive antigen group; DSA, donor specific antibody; DHSA, donor HLA-specific antibody; FCXM, flow cytometric crossmatch; GVHD, graft-versus-host-disease; HLA, human leukocyte antigen; HSCT, hematopoietic stem cell transplant; HTC, homozygous typing cell; IHIWS,International Histocompatibility and Immunogenetics Workshops; IMGT, international ImMunoGeneTics project; MESF, molecules of equivalent soluble fluorochrome; MFI, mean fluorescence intensity; mHags, minor histocompatibility antigens; MHC, major histocompatibility complex; MIC, MHC class I related chain molecule; MLC, mixed lymphocyte culture; NK, natural killer cell; NMDP, National Marrow Donor...