Differential immunogenicity of HLA mismatches in clinical transplantation

Claas, Frans H.J.; Dankers, Marlies K.A.; Oudshoorn, Machteld; Rood, Jon J. van; Mulder, Arend; Roelen, Dave L.; Duquesnoy, René J.; Doxiadis, Ilias I.N.

doi:10.1016/j.trim.2005.03.007

Cited by 71 publications

(57 citation statements)

References 31 publications

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“…Each donor's functional epitope may have one or more residues that may be identified as nonself by the recipient. These residues have been termed ''eplets'' (32)(33)(34)(35). HLAMatchmaker (http://www.hlamatchmaker.net) is a computer algorithm that identifies structural HLA eplet mismatches between donors and recipients that may give rise to anti-HLA antibodies (31,33,(36)(37)(38)(39)(40).…”

Section: Introductionmentioning

confidence: 99%

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

Sapir‐Pichhadze

Tinckam

Quach

et al. 2015

American Journal of Transplantation

116

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We conducted a nested case-control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA-DR and -DQ incompatibility at the eplet level. Cases (n ¼ 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n ¼ 104) with a similar follow-up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios [OR] of 2.84 [95% confidence interval (CI): 1.03, 7.84] and 4.62 [95% CI: 1.51, 14.14]) in the presence of 27-43 and >43 HLA-DR þ DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA-DR þ DQ eplet mismatches. Our study suggests that minimization of HLA-DR þ DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study.

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Section: Introductionmentioning

confidence: 99%

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

Sapir‐Pichhadze

Tinckam

Quach

et al. 2015

American Journal of Transplantation

116

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“…FC CM is the most sensitive immunological method and it allows for the detection of DSA in TC serum. Positive FC CM is associated with an elevated risk of AMR [12,16,17,21,32,[104][105][106][107] . The accurate detection of the spectrum of anti-HLA antibodies is critical for organ allocation and the prediction of FC CM results.…”

Section: Luminex Sa Sp Assay: Technical Challenges Correlation Of Dsamentioning

confidence: 98%

“…In solid organ transplantations of the kidney, heart, lung, and pancreas graft outcomes critically depend on the degree of HLA matching between the donor and recipient [9][10][11][12][13][14][15][16][17] . The cellular components of the allogeneic immune response to the transplanted tissue play a key role in this matching and the contribution of antibodies should not be underestimated [18][19][20][21][22] .…”

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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“…In kidney transplantation, graft outcomes critically depend on the degree of HLA matching between the donor and recipient (Abe et al, 1997;Akalin & Pascual, 2006;Balan et al, 2008;Bas et al, 1998;Claas et al, 2005;Scornik et al, 1992;Takemoto et al, 2004;Terasaki 2003;). Although the cellular component of the allogenic immune response to the transplanted tissue plays a key role in this matching, the contribution of antibodies should not be underestimated Bartel et al, 2007;Stegall et al, 2009;Sumitran-Holgersson, 2001;Vasilescu et al, 2004;Zeevi et al, 2009).…”

Section: Role Of Alloantibodies In Kidney Transplantationmentioning

confidence: 99%

Characteristics, Detection, and Clinical Relevance of Alloantibodies in Kidney Transplantation

Lobashevsky¹

2011

Kidney Transplantation - New Perspectives

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Differential immunogenicity of HLA mismatches in clinical transplantation

Cited by 71 publications

References 31 publications

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

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

Characteristics, Detection, and Clinical Relevance of Alloantibodies in Kidney Transplantation

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