Antibody-mediated rejection in hand transplantation

Weißenbacher, Annemarie; Hautz, Theresa; Zelger, Bernhard; Zelger, Bettina; Mayr, Verena; Brandacher, Gerald; Pratschke, Johann; Schneeberger, Stefan

doi:10.1111/tri.12233

Cited by 61 publications

(45 citation statements)

References 20 publications

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“…Little is known about ABMR and the relevance of DSA, B‐lymphocytes, and C4d staining in VCA. This specific type of rejection has been recently described in a patient after forearm transplantation . Nine years after bilateral forearm transplantation, the patient developed allograft rejection and tested positive for presence of DSA for the first time.…”

Section: Discussionmentioning

confidence: 59%

Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts

et al. 2014

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SummaryThe mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNAd was increased in the endothelium of vessels upon rejection in human skin (P = 0.003) and correlated with B-and T-lymphocyte numbers and LFA-1 expression. PNAd expression was observed at all time-points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNAd expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNAd expression was strongly associated with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO formation can be uniformly found in experimental and human VCA. PNAd expression in vascular endothelium correlates with skin rejection and T-and B-cell infiltration.

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Section: Discussionmentioning

confidence: 59%

Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts

et al. 2014

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“…30,42 In human VCA, DSA may be detected in patients who develop CR (as in 2 of our patients, 1 each with hands and face transplantation), but other patients did not develop DSA. 24,27,28 Of note, AMR due to DSA has been reported in 2 patients with VCA (1 hand and 1 face) 13,43 ; however, these cases were diagnosed with acute, not chronic, rejection. In another hand-grafted patient, who lost his allograft because of GV, DSA were only detected after graft removal, possibly because DSA were bound into the allograft.…”

Section: Pathogenetic Mechanismsmentioning

confidence: 96%

Chronic Rejection in Human Vascularized Composite Allotransplantation (Hand and Face Recipients)

et al. 2016

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Vascularized composite tissue allografts (VCA) have become a viable option to restore severely damaged parts of the body that cannot be repaired with conventional surgical techniques. Acute rejection develops frequently in the early postgraft period both in human and experimental VCA, but the possibility of human VCA to undergo chronic rejection (CR) remained initially unknown. The experience gained over the years shows that, similar to solid organ transplants (SOT), human VCA can also develop CR. Chronic rejection is clinically mostly apparent on the skin and targets preferentially skin and deep vessels, leading, as in SOT, to graft vasculopathy and often to graft loss. Dermal sclerosis and adnexal atrophy are additional features of CR. The pathogenetic immune mechanisms involved (cell-mediated versus humoral) remain incompletely known. The changes of CR can be detected with skin and deep tissue biopsies. Modern in vivo imaging tools can detect vascular narrowing and have the advantage of being noninvasive. However, the diagnosis and treatment of CR remain challenging, as several important questions remain to be answered: a more accurate definition of CR in VCA is needed to establish criteria allowing an accurate and early diagnosis. The pathogenetic mechanisms of CR need to be better understood to allow more efficacious treatment. Favoring/triggering factors of CR need to be better known so that they can be avoided. As in SOT, there is a need for efficient tolerance-inducing protocols that will favor graft acceptance and (ideally) circumvent the necessity of lifelong immunosuppression.

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“…Rituximab (i.e., anti-CD20 antibody) normalized not only clinical symptoms, but also histological findings and DSA levels. [55] Another hand transplantation patient presented with an aggressive thickening of arterial walls, detected by ultrasound biomicroscopy, an advanced imaging technique capable of revealing arterial thickening noninvasively. Further tests correlated findings with the deposition of the complement product C4d.…”

Section: Vascularized Composite Tissue Allotransplantation (Vca) — Rementioning

confidence: 99%

Current status of vascularized composite tissue allotransplantation

Edtinger¹,

Yang²,

Uehara³

et al. 2014

Burn Trauma

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Vascularized composite tissue allotransplantation (VCA) offers treatment options of complex functional deficiencies that cannot be repaired with conventional reconstructive methods. VCAs consist of blocks of functional units comprising different tissue types such as skin, bone, muscle, nerves, blood vessels, tendons, ligaments and others, and are thus substantially different from the composition of organ transplants. The field of VCA has made fascinating progresses in the recent past. Among other VCAs, numerous successful hand, face and limb transplants have been performed in the world. At the same time, specific questions in regard to innate and adaptive immunity, consequences of ischemia/reperfusion injury, immunosuppression, preservation, and regenerative capacity remain. In spite of this, the field is poised to make significant advances in the near future.

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Antibody-mediated rejection in hand transplantation

Cited by 61 publications

References 20 publications

Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts

Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts

Chronic Rejection in Human Vascularized Composite Allotransplantation (Hand and Face Recipients)

Current status of vascularized composite tissue allotransplantation

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