Expansion of Humoral Donor-Specific Alloreactivity After Renal Transplantation Correlates With Impaired Graft Outcome

Varnavidou-Nicolaidou, Agathi; Iniotaki-Theodoraki, A; Doxiadis, Ilias I.N.; Georgiou, Dora; Patargias, Theocharis; Stavropoulos-Giokas, Catherine; Kyriakides, George

doi:10.1016/j.humimm.2005.07.002

Cited by 9 publications

(9 citation statements)

References 13 publications

(15 reference statements)

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“…Figures C and A and B show that the nine renal transplantation recipients studied had little or no antibody specific for fibroblasts of the transplant donor before or after transplantation. This result is consistent with the observations of many cited above and others not cited in this paper, that most recipients of functioning kidney transplants have little or no detectable donor‐specific antibodies in their blood during the early months after transplantation. In contrast, sera obtained from subjects sensitized to a broad range of HLA antigens in the population, as indicated by a high level of PRA, reacted strongly in the fibroblast ELISA (Figure C).…”

Section: Resultssupporting

confidence: 93%

Cryptic B Cell Response to Renal Transplantation

Lynch

Silva

Chen

et al. 2013

American Journal of Transplantation

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Renal transplantation reliably evokes allo-specific B cell and T cell responses in mice. Yet, human recipients of kidney transplants with normal function usually exhibit little or no antibody specific for the transplant donor during the early weeks and months after transplantation. Indeed, the absence of anti-donor antibodies is taken to reflect effective immunosuppressive therapy and to predict a favorable outcome. Whether the absence of donor-specific antibodies reflects absence of a B-cell response to the donor, tolerance to the donor or immunity masked by binding of donor-specific antibodies to the graft is not known. To distinguish between these possibilities, we devised a novel ELISPOT, using cultured donor, recipient and third-party fibroblasts as targets. We enumerated donor-specific antibody-secreting cells in the blood of nine renal allograft recipients with normal kidney function before and after transplantation. Although none of the nine subjects had detectable donor-specific antibodies before or after transplantation, all exhibited increases in the frequency of donor-specific antibody-secreting cells eight weeks after transplantation. The responses were directed against the donor HLA-class I antigens. The increase in frequency of donor-specific antibody-secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought.

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Section: Resultssupporting

confidence: 93%

Cryptic B Cell Response to Renal Transplantation

Lynch

Silva

Chen

et al. 2013

American Journal of Transplantation

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“…Moreover, it was also clear from the results that when there was HLA‐DR and ‐DQ incompatibility, the antibodies that appeared first in the circulation were HLA‐DQ graft specific. These results support the theory about hierarchy in alloantigen recognition post‐Tx as it has been described previously [25–27]. Our observation that the majority of anti‐HLA class II DSA recognized HLA‐DQ graft molecules (64/68 patients) confirms the results of previous studies [20,24,26].…”

Section: Discussionsupporting

confidence: 92%

Long-term follow up for anti-HLA donor specific antibodies postrenal transplantation: high immunogenicity of HLA class II graft molecules

Ntokou¹,

Iniotaki²,

Kontou³

et al. 2011

Transplant International

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Summary Τhe clinical significance of de novo post‐transplant anti‐HLA donor‐specific antibodies (DSA) was evaluated using 4241 serum samples collected between 2000 and 2007 from 597 renal transplant recipients. Patients transplanted before December 1996 (n = 77) were included in the historic group and those transplanted thereafter (n = 520) were included in the study group. All recipients were negative for DSA before transplantation (Tx). Post‐Tx, de novo DSA were detected in 92/597 (15.4%) patients, while 196 had third party anti‐HLA antibodies (DSA‐negative). DSA were more frequent in the historic group (33.8%) compared with the study group (12.7%) (P < 0.001). Anti‐HLA class‐II DSA predominated in both groups (84.6% vs. 69.7%). Recipients of HLA class II‐incompatible grafts developed DSA more frequently than those receiving HLA class II‐compatible grafts (17.9% vs.7.9%, P = 0.003), directed mainly against HLA‐DQ graft molecules (64/446, 14.4%). DSA production was not different between presensitized and nonsensitized patients (P = 0.842). Graft survival was higher in patients without antibodies compared with DSA‐positive (log‐rank test, P = 0.002) and DSA‐negative patients (log‐rank test, P = 0.002). Univariate and multivariate analysis showed independent association for DSA class I (HR = 31.78), DSA class II (HR = 20.92) and non‐DSA (HR = 5.94) and graft failure. We conclude that HLA class II incompatible graft transplantations need careful monitoring and should be avoided in high immunological risk cases.

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“…Hyperacute rejection is caused by a humoral immune response. It is an antibody‐mediated cytotoxic response to the fixation of antibodies to specific MHC class I antigens on vascular endothelium, resulting in complement activation and, finally, in graft injury and rejection 35‐37 . We used a lymphocytotoxicity test, which is routinely used for pretransplant HLA compatibility testing, to assess the effect of HLA silencing on complement‐mediated cell lysis.…”

Section: Discussionmentioning

confidence: 99%