Hyperacute and Acute Kidney Graft Rejection Due to Antibodies Against B Cells

Scornik, Juan C.; Lefor, William M.; Cicciarelli, J; Brunson, Matthew E.; Bogaard, T.; Howard, Richard J.; Ackermann, J. R.; Mendez, Robert; Shires, Dana L.; Pfaff, William

doi:10.1097/00007890-199207000-00010

Cited by 82 publications

(41 citation statements)

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“…The correlation between antibody absence and a low number of mismatched DRB1 eplets (Table 3) suggests many DR antigen mismatches may have a limited potential of inducing a humoral immune response. Another explanation for the low detection rate of circulating anti-HLA-DR antibodies is that they have been absorbed by the allograft which has been shown to express HLA-DR antigens on its endothelium and parenchymal cells [45][46][47][48] and that DRB antibodies can be eluted from rejected transplants [49]. Moreover, anti-DRB antibodies are more readily detected in class II sensitized patients in the absence of a transplanted organ (Table 2), and their frequency of antibody detection is similar to that of HLA-DQ.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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show abstract

“…It is now well recognized that light microscopic findings can be quite subtle even in the presence of circulating donor-specific antibodies. [4][5][6] The conventional immunofluorescence panel of immunoglobulin and complement components has been replaced by the detection of C4d, a single complement degradation product that can independently predict unfavorable graft outcome. [7][8][9][10][11][12][13][14] C4d participates in the classic pathway of complement activation.…”

mentioning

confidence: 99%

Clinical significance of the distribution of C4d deposits in different anatomic compartments of the allograft kidney

et al. 2008

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“…This cutoff, however, may not be sufficient to account for the variability of the test and, to avoid falsepositive results, it is often nescessary to use a relatively high cutoff and sacrifice some sensitivity to gain specificity. Current literature lacks unanimity on FCXM, with several publications not providing their cutoff points and others reporting various shifts above normal control staining intensity (Cicciarelli et al, 1992;Kerman et al, 1990;Ogura et al, 1993;1994;Mahoney et al, 1990). The distinction between weakly positive and negative results is also particularly problematic with the FCXM (Scornik, 1995).…”

Section: Results Evaluationmentioning

confidence: 99%

“…This panel size is not sufficient to identify individual HLA antigen specificities but it is a sensitive way to determine the presence or absence of alloantibodies. The flow cytometry screen has been simplified by mixing several target cells in one tube (Cicciarelli et al, 1992), although this procedure has not become widely accepted. Given the increasing use of the FCXM at the time of transplantation, there is a growing need to perform antibody screens with the same degree of sensitivity.…”

Section: Flow Cytometry Hla Specificitymentioning

confidence: 99%