Significant association between chronic antibody-mediated rejection and donor-specific antibodies against HLA-DRB rather than DQB in renal transplantation

Kobayashi, Takaaki; Maruya, Etsuko; Niwa, Misao; Saji, Hiroh; Kohara, Setsuko; Katayama, Akio; Takeda, Asami; Watarai, Yoshihiko; Uchida, Kazuharu

doi:10.1016/j.humimm.2010.10.018

Cited by 24 publications

(12 citation statements)

References 47 publications

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“…This observation does not necessarily challenge (25,66) the role of HLA-DQ eplet mismatches in the development of TG; but rather sheds lights on the potential diversity of eplet immunogenicity and the unique interactions of HLA-DQB/-DQA chains (in contrast to the single polymorphic HLA-DRB1 chain) with antibodies. While a greater eplet load may indicate a greater risk for experiencing antibody-mediated injuries from de novo DSA, it is the presence (or absence) of highly immunogenic eplet mismatches that help refine this risk.…”

Section: Discussionmentioning

confidence: 78%

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: Discussionmentioning

confidence: 78%

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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“…[26][27][28][29] Interestingly, the current findings indicate that a majority of de novo HLA class I antibodies were non-DSA, which could be explained by the relation between the HLA expression level in endothelial cells and the amount of antibody absorption. 30 As HLA class I, unlike class II (particularly DQ), is regularly expressed in endothelial cells under nonactivated conditions, class I DSA would be absorbed by the graft. Therefore, non-DSA against class I (among widely produced HLA antibodies) and, in contrast, DSA against DQ could be readily detected, which corresponds to previous reports.…”

Section: Discussionmentioning

confidence: 99%

Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation

Ashimine

Watarai

Yamamoto

et al. 2014

Kidney International

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The long-term effect of rituximab and splenectomy on de novo HLA antibody production and chronic antibody-mediated rejection after renal transplantation is uncertain. In order to gain insight on this, we studied 92 ABO-incompatible and 228 ABO-identical/compatible consecutive renal transplant patients and determined their de novo HLA antibody production and graft outcome. Patients with pretransplant donor-specific antibodies had been excluded. ABO-incompatible transplants included 30 recipients treated with rituximab, 51 by splenectomy, or 11 with neither, due to low anti-A or -B antibody titer. Graft survival in ABO-identical/compatible patients (97.7% at 5 years) was significantly higher than in ABO-incompatible (87.0% at 5 years), rituximab (96.7% at 3 years), or splenectomy (85.7% at 5 years) patients. Only four patients had clinical chronic antibody-mediated rejection (two each identical/compatible and incompatible). There was no significant difference in prevalence of de novo HLA antibody, including donor-specific and nondonor-specific antibodies among ABO-identical/compatible patients (13.9%), patients receiving rituximab (14.3%) or splenectomy (13.2%), or among those receiving cyclosporine, tacrolimus, mycophenolate mofetil, mizoribine, and everolimus. Renal function remained stable in most recipients with de novo HLA antibody. Thus, neither pretransplant splenectomy nor rituximab treatment has an inhibitory effect on de novo HLA antibody production during medium-term follow-up. Further study on long-term effects is needed.

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“…These studies report that DSA develop in 15%-30% of patients. Anti HLA-DQ DSA develops in 55-77% of patients with DSA and in 50%-66% of patients who lost their graft [6][7][8][9][10][11][12][13][14][15][16][17]. In most of these studies the development of DSA was associated with worst graft outcomes.…”

Section: Role Of Anti Dq Antibodies After Transplantationmentioning

confidence: 99%

Anti-human leukocyte antigen DQ antibodies in renal transplantation: Are we underestimating the most frequent donor specific alloantibodies?

Carta

Maria

Caroti

et al. 2015

Transplantation Reviews

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Significant association between chronic antibody-mediated rejection and donor-specific antibodies against HLA-DRB rather than DQB in renal transplantation

Cited by 24 publications

References 47 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

Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation

Anti-human leukocyte antigen DQ antibodies in renal transplantation: Are we underestimating the most frequent donor specific alloantibodies?

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