CD3+-Mediated Rejection and C4d Deposition in Two Composite Tissue (Bilateral Hand) Allograft Recipients After Induction With Alemtuzumab

Landín, Luis; Cavadas, Pedro C.; Ibáñez, Javier; Roger, Ignacio; Vera-Sempere, Francisco

doi:10.1097/tp.0b013e318198dbc7

Cited by 59 publications

(35 citation statements)

References 25 publications

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“…For instance, although Landin et al (13) reported positive C4d allograft staining during acute rejection of a hand transplant, it was in the absence of DSA and found to also be present in unaffected areas or at times of no clinical rejection. Similarly, in a series of six hand recipients, Kaufman et al (7) reported C4d staining to be ''nonspecific and uninformative'' in five of the recipients; the sixth recipient was thought to have C4d staining specific to the allograft but in the absence of DSA (7).…”

Section: Discussionmentioning

confidence: 99%

The Management of Antibody-Mediated Rejection in the First Presensitized Recipient of a Full-Face Allotransplant

Chandraker

Arscott

Murphy

et al. 2014

American Journal of Transplantation

102

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y Both authors contributed equally.We report on the management of the first full-face transplantation in a sensitized recipient with a positive preoperative crossmatch and subsequent antibodymediated rejection (AMR). The recipient is a 45-year-old female who sustained extensive chemical burns, with residual poor function and high levels of circulating anti-HLA antibodies. With a clear immunosuppression plan and salvage options in place, a full-face allotransplant was performed using a crossmatch positive donor. Despite plasmapheresis alongside a standard induction regimen, clinical signs of rejection were noted on postoperative day 5 (POD5). Donor-specific antibody (DSA) titers rose with evidence of C4d deposits on biopsy. By POD19, biopsies showed Banff Grade III rejection. Combination therapy consisting of plasmapheresis, eculizumab, bortezomib and alemtuzumab decreased DSA levels, improved clinical exam, and by 6 months postop she had no histological signs of rejection. This case is the first to demonstrate evidence and management of AMR in face allotransplantation. Our findings lend support to the call for an update to the Banff classification of rejection in vascularized composite tissue allotransplantation (VCA) to include AMR, and for further studies to better classify the histology and mechanism of action of AMR in VCA.

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Section: Discussionmentioning

confidence: 99%

The Management of Antibody-Mediated Rejection in the First Presensitized Recipient of a Full-Face Allotransplant

Chandraker

Arscott

Murphy

et al. 2014

American Journal of Transplantation

102

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“…Patients: Detailed descriptions of patients and the clinical courses were published previously (3)(4)(5)11,12). In brief, five patients (four male and one Efomycine M: Efomycine M was purified as described earlier (15,16 Figure 1F) and did not correlate with severity of rejection (cc = −0.071).…”

Section: Investigation Of Human Hand Allograft Skin Biopsiesmentioning

confidence: 99%

Molecular Markers and Targeted Therapy of Skin Rejection in Composite Tissue Allotransplantation

Hautz¹,

Zelger²,

Grahammer³

et al. 2010

American Journal of Transplantation

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Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E-and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E-and P-selectin in the skin holds potential to significantly prolong limb allograft survival.

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“…A similar situation has been observed in a recalcitrant infection due to human papilloma virus (HPV) in the allograft of a recipient of HA, that required aggressive treatment due to viral resistance [40]. A repetitive cutaneous varicella zoster infection was also observed in a HA recipient, requiring long-term prophylaxis with acyclovir [30]. Other recipients of FAs have shown non-systemic worrying infection due to herpes simplex virus (HSV) at the lip [23 • …”

Section: Importance Of Infectionmentioning

confidence: 86%

“…It is also unclear whether antibodies play a significant role in rejection of VCAs. Marker of antibody mediated rejection (AMR) C4d has been found by a few teams in the allografts, but others were not able to determine [30,34]. The team from Louisville was able to determine that DSA raised after HA removal due to CR [31, 32 • ].…”

Section: Importance Of Rejectionmentioning

confidence: 99%

Alloimmune and Infectious Complications in Hand/Face Transplantation

2013

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Vascularized composite allograft transplantation was definitively introduced in the armamentarium of reconstructive surgery in 1998. The development of potent immunosuppressive regimens permitted allograft survival, but rejection and infectious complications remain important issues. Our aim is to provide useful information on immunosuppression, rejection and infectious complications, their clinical management and their repercussion on the functional outcomes and allograft regeneration. Reports that gather current knowledge are included and commented. Current surgical strategies to control perioperative infections in hand and face transplantation are discussed. The implantation of reconstructive transplantation depends much on the control of rejection and infectious complications for the safety of the patients.

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CD3+-Mediated Rejection and C4d Deposition in Two Composite Tissue (Bilateral Hand) Allograft Recipients After Induction With Alemtuzumab

Abstract: These findings suggest that alemtuzumab may not prevent cell-mediated rejection of a hand allograft transplant. Furthermore, C4d deposition warrants attention in clinical composite tissue allotransplants.

Cited by 59 publications

References 25 publications

The Management of Antibody-Mediated Rejection in the First Presensitized Recipient of a Full-Face Allotransplant

The Management of Antibody-Mediated Rejection in the First Presensitized Recipient of a Full-Face Allotransplant

Molecular Markers and Targeted Therapy of Skin Rejection in Composite Tissue Allotransplantation

Alloimmune and Infectious Complications in Hand/Face Transplantation

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