Humoral Theory of Transplantation

Terasaki, Paul I.

doi:10.1034/j.1600-6143.2003.00135.x

Cited by 547 publications

(423 citation statements)

References 120 publications

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“…The important role of these anti-HLA AlloAb in mediating rejection had been emphasized first by Terasaki. 1 The antibodies found in the peripheral circulation were not necessarily donor-specific, and their association with failure was consistent with a causality hypothesis. 2 Several studies observed that patients who had rejected transplants displayed anti-HLA antibodies more frequently than those with functioning grafts.…”

supporting

confidence: 60%

Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

Viana¹,

Nolasco²,

Santos³

et al. 2009

Transplantation Proceedings

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Background. Prospective testing for posttransplant circulating anti-HLA antibodies seems to be a critical noninvasive tool, but confirmatory data are lacking. Materials and Methods. Over the last 3 years, peritubular capillary (PTC) C4d deposition was prospectively sought by an immunofluorescence technique applied to frozen tissue in biopsies obtained for allograft dysfunction. Screening for circulating anti-HLA class I/II alloantibodies (AlloAb) by the flow cytometric test was performed simultaneously. Results. We evaluated 132 sets of biopsies and simultaneous serum samples. PTC C4d deposition was demonstrated in 15.9% (21/132) of biopsies. Circulating anti-HLA I/II AlloAb were detected in 25% (33/132) of serum samples. Employing receiver-operator characteristic (ROC) curves for all C4d-positive biopsies, screening for AlloAb showed a global specificity of 82% and sensitivity of 61.9%. When this analysis was restricted to biopsies obtained in the first month posttransplantation, the sensitivity increased to 81.8%, but the specificity decreased to 76.9%. After the first month posttransplantation, we observed sensitivity of 40.0% and a specificity of 86.4%. In the first month posttransplantation, all patients with a diagnosis of acute antibody-mediated rejection displayed circulating anti-HLA class I/II, but not always at the same time as the C4d-positive biopsy. Conclusions. In the first month posttransplantation, prospective monitoring of anti-HLA antibodies may be useful. The high sensitivity allows the identification of patients at risk, affording an earlier diagnosis of antibody-mediated rejection. After the first month, the test can be used to evaluate allograft dysfunction episodes, since positivity is highly suggestive of an antibody-mediated process.

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supporting

confidence: 60%

Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

Viana¹,

Nolasco²,

Santos³

et al. 2009

Transplantation Proceedings

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“…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

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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.

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“…1 At present the exact mechanism of this chronic allograft rejection is not clear, but it has become evident that both innate and adaptive immune responses play an important role in the onset and pathogenesis of BOS. [2][3][4][5] Natural killer (NK) cells are one of the main cellular components of the innate immune system and are important in the lysis of virally infected cells and tumors. The NK cells express a multitude of intracellular and extracellular proteins in order to recognize and eliminate target cells.…”

mentioning

confidence: 99%

The Killer Immunoglobulin-Like Receptor (KIR) Group A Haplotype is Associated With Bronchiolitis Obliterans Syndrome After Lung Transplantation

Erp

Graaf

Paantjens

et al. 2008

The Journal of Heart and Lung Transplantation

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Background:The development of bronchiolitis obliterans syndrome (BOS) after lung transplantation is associated with viral infections. Natural killer (NK) cells are involved in the lysis of viral infected cells, and their activation is largely controlled by activating and inhibitory killer immunoglobulin-like receptors (KIRs). We hypothesized that KIR ligand incompatibility and recipients' individual KIRs could influence the development of BOS and the incidence of cytomegalovirus reactivation after lung transplantation. Methods:The KIR gene contents were determined in 48 patients who received a lung transplant, and human leukocyte antigen (HLA)-Cw and HLA-Bw4 typing was performed on their respective donors. Results:BOS developed in 7 patients and cytomegalovirus reactivation occurred in 16. BOS developed in 5 of 19 patients homozygous for KIR haplotype A compared with 2 of 27 patients with KIR haplotype AB and B (homozygous; p ϭ 0.03; log-rank test). In none of the patients with BOS was the activating KIR2DS5 gene detected, whereas it was present in 35% of patients without BOS (p ϭ 0.04; log-rank test). No correlation was found between KIR gene content and cytomegalovirus reactivation. Conclusion: Our results suggest that the lack of activating KIRs may play an important role in the development of BOS but not in the control of cytomegalovirus reactivation after lung transplantation.

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Humoral Theory of Transplantation

Cited by 547 publications

References 120 publications

Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

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

The Killer Immunoglobulin-Like Receptor (KIR) Group A Haplotype is Associated With Bronchiolitis Obliterans Syndrome After Lung Transplantation

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