All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies

Lee, Po Chang; Terasaki, Paul I.; Takemoto, Steven K.; Lee, Po‐Huang; Hung, Chung Jye; Chen, Yi Lin; Tsai, Alen; Lei, Huan Yao

doi:10.1097/00007890-200210270-00025

Cited by 296 publications

(251 citation statements)

References 6 publications

Supporting

Mentioning

228

Contrasting

Unclassified

Order By: Relevance

“…Whereas the robust antibody response in early AMR results in complement-mediated lytic injury of the endothelium and rapidly progressive allograft dysfunction allowing an early diagnosis, the smoldering generation of de novo DSA observed in late AMR results in nonlytic complementmediated injury, partial accommodation, and slow allograft dysfunction. [25][26][27][28] Whether the differences in the nature of the Table 3. CLINICAL RESEARCH www.jasn.org immune response influence the response to therapy in these entities has yet to be studied.…”

Section: Discussionmentioning

confidence: 99%

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

Pascual¹,

Samaniego²,

Torrealba³

et al. 2008

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

The prevalence, risk factors, and outcome of antibody-mediated rejection (AMR) of the kidney after simultaneous pancreas-kidney transplantation are unknown. In 136 simultaneous pancreas-kidney recipients who were followed for an average of 3.1 yr, 21 episodes of AMR of the kidney allograft were identified. Eight episodes occurred early (Յ90 d) after transplantation, and 13 occurred later. Histologic evidence of concomitant acute cellular rejection was noted in 12 cases; the other nine had evidence only of humoral rejection. In 13 cases, clinical rejection of the pancreas was diagnosed simultaneously, and two of these were biopsy proven and were positive for C4d immunostaining. Multivariate analysis identified only one significant risk factor: Female patients were three times more likely to experience AMR. Nearly all early episodes resolved with treatment and did not predict graft loss, but multivariate Cox models revealed that late AMR episodes more than tripled the risk for kidney and pancreas graft loss; therefore, new strategies are needed to prevent and to treat late AMR in simultaneous pancreaskidney transplant recipients.

show abstract

Section: Discussionmentioning

confidence: 99%

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

Pascual¹,

Samaniego²,

Torrealba³

et al. 2008

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…TG develops as a consequence of overt and covert episodes of antibody-mediated rejection (5,(18)(19)(20)(21)(22)(23)(24), typically, due to HLA class II anti-HLA antibodies (5,10,(25)(26)(27)(28)(29)(30). Antibodies against HLA develop when antibody-accessible polymorphic residues on HLA antigens are recognized as ''nonself.''…”

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

View full text Add to dashboard Cite

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.

show abstract

“…Preformed anti-donor class II antibodies increase the risk of transplant failure [1][2][3][4][5][6][7][8][9] and the post-transplant development of anti-class II antibodies is associated with a higher incidence of acute and chronic rejection [10][11][12][13][14][15][16][17][18][19] Current class II matching strategies for kidney transplantation consider only the HLA-DR antigens controlled by the DRB1 locus but mismatching for HLA-DQ and HLA-DP may also lead to lower graft survival rates [20][21][22][23][24][25]. Newer serum screening methods such as ELISA, Flow Cytometry and Luminex have greatly enhanced the detection of anti-HLA-DQ and HLA-DP antibodies and their association with transplant rejection [2,7,[26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Duquesnoy

Awadalla

Lomago

et al. 2008

Transplant Immunology

View full text Add to dashboard Cite

This report describes a detailed analysis how donor-specific HLA class II epitope mismatching affects antibody reactivity patterns in 75 solid organ transplant recipients with an in situ allograft and who were considered for retransplantation. Sera were tested for antibodies in a sensitive antigenbinding assay (Luminex) with single class II alleles. Their reactivity was analyzed with HLAMatchmaker, a structural matching algorithm that considers so-called eplets to define epitopes recognized by antibodies. Only 24% of the patients showed donor-specific anti-DRB1 antibodies and there was a significant correlation with a low number of mismatched DRB1 eplets. This low detection rate of anti-DRB1 antibodies may also be due to allograft absorption. In contrast, antibodies to DRB3/4/5 mismatches were more common. Especially, 83% of the DRB4 (DR53) mismatches resulted in detectable antibodies against an eplet uniquely found on DR53 antigens. Donor-specific DQB mismatches led to detectable anti-DQB antibodies with a frequency of 87%. Their specificity correlated with eplets uniquely found on DQ1-4. The incidence of antibodies induced by 2-digit DQA mismatches was 64% and several eplets appeared to play a dominant role. These findings suggest that both α and β chains of HLA-DQ heterodimers have immunogenic epitopes that can elicit specific antibodies. About one-third of the sera had anti-DP antibodies; they reacted primarily with two DPB eplets and an allelic pair of DPA eplets.These data demonstrate that HLA class II reactive sera display distinct specificity patterns associated with structurally defined epitopes on different HLA-D alleles.

show abstract

All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies

Abstract: HLA antibodies were found in 29 consecutive cases of chronic rejection failures as much as one year before the loss of grafts. We conclude that HLA antibodies may be a prerequisite for chronic immunologic rejection.

Cited by 296 publications

References 6 publications

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

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

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Contact Info

Product

Resources

About